{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3112-main", "verdict_number": "3112", "title": "Oral vitamin B12 as the sole added active ingredient × Improvement in global cognition in adults with clinically defined MCI", "view_version": "1.0", "view_created_date": "2026-11-05", "criteria_version": "NGM-v3112-ORAL-B12-MCI-GLOBAL-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-16", "review_scope": { "materials_read": "Stored Korean and English manuscripts and case-specific criteria and application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "No new external clinical abstracts, full texts, registrations or statistical analysis plans were read. The stored records are distinguished from the links made for this public presentation, and the original verdict, numbers and unverified information are preserved. No new search, calculation or reassessment was performed.", "date_meaning": "This is the date the stored materials were checked, not the date of an up-to-date clinical literature search." }, "claim_context": { "population": "Adults with clinically defined MCI; distinguish correction of deficiency from supplementation in replete or unverified status; detailed Ma2019 criteria and baseline status unverified", "intervention": "Vitamin B12: the sole randomized added active ingredient · Question concerns an oral single-ingredient preparation; chemical form, tablet/capsule and release formulation in the Ma2019 monotherapy arm unverified · Oral only; sublingual, intramuscular and intravenous routes excluded", "dose": "No amount per administration (1 time) or daily amount established from direct original material; the review's 25 µg/day is an unverified lead", "comparator": "Matched placebo, no added B12 or usual care on the same background; an untreated control was reported in Ma2019; the add-on comparison on a folic acid background remains unconfirmed until the same background is verified", "endpoint": "The between-group difference in change or adjusted endpoint difference in WAIS-RC Full Scale IQ at 6 months is fixed as the outcome to review; registered primary (1st) status and an eligible monotherapy estimate are unverified", "duration": "Page review timepoint: 6 months; this is the period reported in Ma2019, and whether it was the prespecified main timepoint is unverified", "excluded_extensions": [ "The main question is the between-group comparison of global cognition scores with B12 as the sole added active ingredient. Correction of biochemical deficiency, combined B vitamins, mixed routes, dementia/imaging/domain scores and uncontrolled before-and-after results are not pooled as direct efficacy evidence; individual harm criteria are applied as supplementary safety boundaries." ] }, "requirements": [ { "item_id": "N01", "question_type": "Claim and boundaries of the distinct question", "question": "Which MCI population, B12 comparison and global cognition outcome does this table address?", "needed": "Original claim and fixed question; specifications of population, ingredient, route, outcome, comparator and timepoint", "role": "Required", "role_reason": "Required to avoid combining the page's cognition, dementia and deficiency questions into a single efficacy claim.", "application_exception": "Verification of the claim boundaries does not establish an eligible trial or an improvement effect.", "criterion": "Link the oral comparison in MCI with B12 as the sole added active ingredient to the global cognition score, and exclude other questions.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Subsequent research should first specify clinical MCI and the between-group effect of interest on a global cognition scale, with conversion to dementia, imaging and biochemical outcomes reported separately.", "current_reports": [], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The current claim concerns improvement in global cognition scores in adults with clinical MCI. It is fixed as a single question comparing an oral regimen with B12 as the sole randomized added active ingredient against a control on the same background. subclaims is an empty list.", "condition_status": "Met", "status_reason": "The original claim and the boundaries of the distinct question were linked. This does not mean an efficacy estimate was verified.", "missingness": "Actual eligible monotherapy-arm results and the prespecified main timepoint remain separately unverified.", "uncertainty": "Actual eligible monotherapy-arm results and the prespecified main timepoint remain separately unverified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original claim and fixed question; specifications of population, ingredient, route, outcome, comparator and timepoint" }, { "item_id": "N02", "question_type": "Clinical MCI diagnosis", "question": "Does the MCI label in Ma2019 satisfy the actual clinical diagnostic criteria?", "needed": "Original material on the diagnostic system, diagnostician, objective criteria, ADL, dementia exclusion, subtypes and age/sex", "role": "Required", "role_reason": "Required to avoid treating the diagnostic label alone as verification of confirmed MCI, preserved daily functioning or exclusion of dementia.", "application_exception": "Do not turn unverified detailed criteria into a definite conclusion that the participants did not have clinical MCI.", "criterion": "Assess population directness by distinguishing the reported MCI label from unverified diagnostic details.", "basis": "M03 §3.2.1; detailed population criteria are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Document diagnostic criteria and procedures for assessing daily functioning and excluding dementia, prespecify MCI subtypes and present results by population.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Ma2019 reported the population as having MCI. The diagnostic system, diagnostician, thresholds, preserved ADL, exclusion of dementia, subtypes, age range and sex distribution are unverified.", "condition_status": "Partly verified", "status_reason": "The MCI label is preserved, but details of clinical eligibility are unverified.", "missingness": "The label cannot substitute for evidence of diagnostic details.", "uncertainty": "The label cannot substitute for evidence of diagnostic details.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original material on the diagnostic system, diagnostician, objective criteria, ADL, dementia exclusion, subtypes and age/sex" }, { "item_id": "N03", "question_type": "Baseline B12 status", "question": "Can correction of deficiency be distinguished from supplementation in replete or unverified status?", "needed": "Baseline B12/holotranscobalamin/MMA, homocysteine, folate, Hb/MCV, deficiency thresholds and results by stratum", "role": "Required", "role_reason": "Required to avoid extending correction of deficiency-related cognitive impairment to MCI efficacy regardless of status.", "application_exception": "Do not fill in unreported baseline tests with assumptions of replete status or normal hematologic status.", "criterion": "Link only the verified scope of baseline status, thresholds and direct results in each stratum.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Prespecify baseline B12 status categories, and separately analyze interactions/stratified comparisons for correction of deficiency and add-on treatment in replete status.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "In Ma2019, baseline serum B12, functional markers, folate, hematologic status, deficient/borderline/replete thresholds and results by stratum are unverified.", "condition_status": "Unverified", "status_reason": "The clinical MCI label alone cannot establish effects by B12 status.", "missingness": "Do not infer efficacy regardless of status or the absence of anemia.", "uncertainty": "Do not infer efficacy regardless of status or the absence of anemia.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Baseline B12/holotranscobalamin/MMA, homocysteine, folate, Hb/MCV, deficiency thresholds and results by stratum" }, { "item_id": "N04", "question_type": "Chemical form and product identity", "question": "Were the actual chemical form, formulation and product in the B12 monotherapy arm verified?", "needed": "Original records of chemical form, salt, manufacturer, dosage/release formulation, product, batch and purity", "role": "Required", "role_reason": "Required to avoid combining different cobalamin chemical forms and products as the same intervention.", "application_exception": "Distinguish the question's definition of a single active ingredient from verification of the actual trial product.", "criterion": "Link the actual product attributes of the monotherapy arm to original material, retaining missing values.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Use an identifiable single-ingredient B12 formulation and report product, batch, purity and exposure to the chemical form by arm.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The chemical form, salt, manufacturer, tablet/capsule, release formulation, product, batch and purity in the Ma2019 monotherapy arm are all unverified.", "condition_status": "Unverified", "status_reason": "cyanocobalamin, methylcobalamin/mecobalamin, hydroxocobalamin and adenosylcobalamin were not verified as the same preparation.", "missingness": "Do not fill in the chemical form from another trial or an official warning.", "uncertainty": "Do not fill in the chemical form from another trial or an official warning.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original records of chemical form, salt, manufacturer, dosage/release formulation, product, batch and purity" }, { "item_id": "N05", "question_type": "Plant part not applicable", "question": "Should this question require distinctions between plant parts?", "needed": "Distinction between a chemical nutrient intervention and a plant-derived intervention", "role": "Supplementary", "role_reason": "Considered to avoid mechanically imposing a plant-part criterion on a chemical nutrient question.", "application_exception": "Nonapplicability of plant part does not waive verification of the manufacturer, product or purity.", "criterion": "Link the retained reason that plant_part is not applicable to the chemical ingredient question.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Obtain actual B12 product and chemical-form material to assess identity criteria without adding plant-part research.", "current_reports": [], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The retained structure records plant_part as not_applicable and explains that a chemical nutrient is not a plant-part intervention.", "condition_status": "Not applicable", "status_reason": "The plant-part criterion does not apply to this narrow B12 question.", "missingness": "Product, manufacturer and purity remain unverified in N04.", "uncertainty": "Product, manufacturer and purity remain unverified in N04.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Distinction between a chemical nutrient intervention and a plant-derived intervention" }, { "item_id": "N06", "question_type": "Oral route", "question": "Was oral administration in the B12 monotherapy arm verified from original material?", "needed": "Route, formulation and schedule by arm, and the original methods for the monotherapy arm", "role": "Required", "role_reason": "Required to avoid treating the word oral for the combination arm as verification of the monotherapy arm's route.", "application_exception": "Distinguish the review's oral-route lead from verification of the original monotherapy arm.", "criterion": "Distinguish the page's oral-route question from the actual oral combination arm and the unverified monotherapy arm.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Specify oral administration and its schedule in the monotherapy arm, and report injection, sublingual and mixed routes as separate comparisons.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The structured route value is oral_combination; single_B12_arm_unverified. The original conclusion's oral-combination wording and the secondary (2nd) review's lead on oral monotherapy are preserved; the original monotherapy arm's route remains unverified.", "condition_status": "Partly verified", "status_reason": "Some route leads exist, but there is no independent verification from original material for the monotherapy arm.", "missingness": "Do not turn the oral scope of the question into a record verifying the actual route in every arm.", "uncertainty": "Do not turn the oral scope of the question into a record verifying the actual route in every arm.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Route, formulation and schedule by arm, and the original methods for the monotherapy arm" }, { "item_id": "N07", "question_type": "Actual dose and secondary (2nd) leads", "question": "Can 25 µg/day be used as the established monotherapy-arm dose?", "needed": "Original amount per administration (1 time), daily amount and frequency in the monotherapy arm, and the original source cited by the review", "role": "Required", "role_reason": "Required to avoid turning the review's dose lead into a verified value for the original monotherapy arm or a personal dose.", "application_exception": "Retain the lead without promoting it to an established daily amount, amount per administration (1 time) or frequency.", "criterion": "Distinguish the reports of B12 25 µg and folic acid 800 µg as secondary (2nd) information, and preserve the unverified original monotherapy-arm dose.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Report chemical form, amount per administration (1 time), frequency and daily amount by arm, and formulate a separate question when conducting a direct dose comparison.", "current_reports": [ "S11", "S13" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The review's B12 25 µg/day and folic acid 800 µg/day are leads for checking original material. The original monotherapy arm's amount per administration (1 time), daily amount and administration frequency are unverified.", "condition_status": "Unverified", "status_reason": "The structure explicitly states secondary_report_only_not_primary_verified and not_used_as_actual_trial_dose.", "missingness": "Do not use these values to determine a personal or optimal dose.", "uncertainty": "Do not use these values to determine a personal or optimal dose.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original amount per administration (1 time), daily amount and frequency in the monotherapy arm, and the original source cited by the review" }, { "item_id": "N08", "question_type": "Same folic acid background", "question": "Does the combination-arm versus folic-acid-arm comparison differ only in B12?", "needed": "Folic acid dose, same background treatment, added ingredients and actual exposure in both C02 arms", "role": "Required", "role_reason": "Required to avoid attributing multiple active ingredients or different backgrounds to an added B12 effect.", "application_exception": "Do not automatically exclude the comparison: if folic acid dose and background are the same in both arms, it may be a candidate for an added B12 effect.", "criterion": "Interpret the contrast as B12 being the sole added ingredient only when the matched background is verified.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Randomize only added B12 on the same folic acid and usual-care background, and prespecify analysis of the same global cognition effect.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "A post hoc comparison states that the combination arm performed better than the folic acid arm, but matching folic acid doses, a common background and the actual contribution of the sole added ingredient are unverified.", "condition_status": "Unverified", "status_reason": "The conditional candidate for added B12 is preserved but is not currently counted as a directly eligible result.", "missingness": "Do not delete the favorable statement or assume matching backgrounds.", "uncertainty": "Do not delete the favorable statement or assume matching backgrounds.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Folic acid dose, same background treatment, added ingredients and actual exposure in both C02 arms" }, { "item_id": "N09", "question_type": "Actual control arm", "question": "Was an untreated control distinguished from matched placebo and the same care?", "needed": "Actual treatment, placebo composition, background and rescue treatment in the control arm", "role": "Required", "role_reason": "Required to avoid presenting an untreated arm as a blinded matched placebo arm.", "application_exception": "Do not erase the existence of the actual untreated arm because placebo composition is unverified.", "criterion": "Distinguish the reported untreated control from the page's eligible comparator criteria.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Document the actual treatment and the same background in the comparator of interest, and examine differences in contact and assessment in the analysis.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "An untreated control was reported in Ma2019. Matched placebo composition and the common background across arms are unverified.", "condition_status": "Partly verified", "status_reason": "Part of the actual control type was verified, but the background and placebo conditions matching the question were not.", "missingness": "Do not substitute an untreated control for a fully matched placebo or usual-care comparison.", "uncertainty": "Do not substitute an untreated control for a fully matched placebo or usual-care comparison.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Actual treatment, placebo composition, background and rescue treatment in the control arm" }, { "item_id": "N10", "question_type": "Adherence and concurrent exposure", "question": "Were actual total B12 exposure and conditions affecting absorption or concomitant use distinguished?", "needed": "Records by arm of adherence/measurement method, diet/fortification/additional supplements, malabsorption and metformin/PPI", "role": "Required", "role_reason": "Required to avoid confusing diet, other supplements and conditions affecting absorption with the randomized dose.", "application_exception": "Do not fill in unreported information with normal absorption, high adherence or absence of concomitant use.", "criterion": "Distinguish the nominal intervention from actual exposure and background differences according to their verification level.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Track exposure, adherence, absorption and concomitant medications, and prespecify separate analyses of the assignment effect and adherence-related effects.", "current_reports": [ "S01", "S03", "S14" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Adherence, diet/fortified foods, concurrent supplementation, total B12 exposure, malabsorption and metformin/PPI use are unverified in the core candidate.", "condition_status": "Unverified", "status_reason": "No direct records are available to examine differences in background exposure or absorption between arms.", "missingness": "Do not transfer official information about these influences into facts about individual concomitant use in Ma2019.", "uncertainty": "Do not transfer official information about these influences into facts about individual concomitant use in Ma2019.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Records by arm of adherence/measurement method, diet/fortification/additional supplements, malabsorption and metformin/PPI" }, { "item_id": "N11", "question_type": "Reported duration and main timepoint", "question": "Was the reported 6-month timepoint verified as the prespecified main timepoint?", "needed": "Administration period, assessment timepoints, registered main timepoint and records of endpoint changes", "role": "Required", "role_reason": "Required to avoid confusing the reported duration with the prespecified main analysis timepoint.", "application_exception": "Preserve the page's 6-month review timepoint without labeling it as the registered main timepoint.", "criterion": "Distinguish the 6-month report from the verification level of preregistration and analysis timepoints.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Prespecify the main assessment timepoint for global cognition, and report later timepoints and follow-up after discontinuation as separate analyses.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The administration period and the page review timepoint are recorded as 6 months. The prespecified main timepoint and actual main analysis timepoint are unverified.", "condition_status": "Partly verified", "status_reason": "The reported duration is verified, but the prespecified hierarchy of timepoints is not.", "missingness": "The duration of 6 months alone does not establish a sustained effect or an optimal duration.", "uncertainty": "The duration of 6 months alone does not establish a sustained effect or an optimal duration.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Administration period, assessment timepoints, registered main timepoint and records of endpoint changes" }, { "item_id": "N12", "question_type": "Global scale and measurement", "question": "Were the actual testing conditions for WAIS-RC FSIQ verified?", "needed": "Scale version/manual, score range, language, education adjustment, administration/practice effects and direction", "role": "Required", "role_reason": "Required to avoid substituting another cognitive scale or a domain result for the same global score outcome.", "application_exception": "Preserve the reported scale and direction without inferring its version or score range.", "criterion": "Distinguish the reported WAIS-RC FSIQ from unverified testing conditions.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Administer the same validated global scale using standardized procedures, with prespecified handling of education, language and repeated-testing effects.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "WAIS-RC FSIQ is reported as a global cognition measure, with higher scores indicating improvement. The exact version, range, language, education adjustment and control of practice effects are unverified.", "condition_status": "Partly verified", "status_reason": "The scale name and direction are available, but actual administration conditions are not sufficiently verified.", "missingness": "Do not substitute MoCA, MMSE or a single memory domain for this outcome.", "uncertainty": "Do not substitute MoCA, MMSE or a single memory domain for this outcome.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Scale version/manual, score range, language, education adjustment, administration/practice effects and direction" }, { "item_id": "N13", "question_type": "Registration and prespecified hierarchy", "question": "Was the prespecified primary endpoint on the global scale checked against the ChiCTR record?", "needed": "Original registration date, original/changed endpoints, protocol, SAP and reasons for changes", "role": "Required", "role_reason": "Required to avoid treating the existence of a registration number as successful comparison against the protocol/SAP.", "application_exception": "Distinguish historical access failure from access not attempted in this exercise, without establishing nonregistration or selective reporting.", "criterion": "Label primary status only according to the hierarchy actually obtained, and retain the unavailable information as such.", "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Link the registration, protocol and SAP in advance and make the original/changed endpoints available for comparison with reported results.", "current_reports": [ "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "ChiCTR-ROC-16008305 is linked, but the original registration date, endpoints, amendments and SAP were not verified. The registration was not newly opened in this task.", "condition_status": "Unverified", "status_reason": "The retained record is inaccessible_registry; current web access/reading has not been attempted.", "missingness": "Do not construct a primary-endpoint hierarchy from search snippets or the registration number alone.", "uncertainty": "Do not construct a primary-endpoint hierarchy from search snippets or the registration number alone.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original registration date, original/changed endpoints, protocol, SAP and reasons for changes" }, { "item_id": "N14", "question_type": "Design and allocation", "question": "Were the actual sequence and allocation concealment for the 4-arm randomization verified?", "needed": "Allocation sequence, concealment, baseline balance and recruitment/selection procedures by arm", "role": "Required", "role_reason": "Required to avoid claiming that the randomized-trial label alone resolves allocation bias concerns.", "application_exception": "Retain the report of randomization and do not turn unverified information into a high-risk judgment.", "criterion": "Link the report of 4-arm randomization to the verification level of the actual allocation methods.", "basis": "M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Disclose the allocation sequence, concealment and baseline characteristics by arm, and prespecify analysis of the assignment effect.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Ma2019 was reported as a 4-arm randomized single-blind trial. The actual sequence, allocation concealment and baseline balance are unverified.", "condition_status": "Partly verified", "status_reason": "The design label is verified, but direct methods material on the allocation process is unavailable.", "missingness": "Do not assign an official RoB score or a new bias grade.", "uncertainty": "Do not assign an official RoB score or a new bias grade.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Allocation sequence, concealment, baseline balance and recruitment/selection procedures by arm" }, { "item_id": "N15", "question_type": "Blinding and assessors", "question": "Who was blinded in the single-blind design?", "needed": "Participant/assessor/analyst blinding, procedures and contact by arm", "role": "Required", "role_reason": "Required to examine cognitive testing and differences in expectations/contact between arms.", "application_exception": "Do not turn unverified information about who was blinded into a definite finding of blinding failure.", "criterion": "Distinguish the single-blind label from unverified information about each role and assessment conditions.", "basis": "M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Specify blinding of cognitive assessors and analysts and contact by arm, and maintain matching assessment procedures.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The single-blind label is preserved, but who was blinded is unverified.", "condition_status": "Partly verified", "status_reason": "The blinding label was not used as a substitute for verification of who was actually blinded.", "missingness": "Do not turn unverified information into a definite conclusion of success or failure.", "uncertainty": "Do not turn unverified information into a definite conclusion of success or failure.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Participant/assessor/analyst blinding, procedures and contact by arm" }, { "item_id": "N16", "question_type": "Allocation and historical arithmetic denominators", "question": "Were 240 participants, 4 arms and the inferred 60 participants distinguished from analysis denominators?", "needed": "Flow diagram of actual allocation, completion and analysis overall/by arm, distinguished from the historical calculation", "role": "Required", "role_reason": "Required to avoid turning the total randomized number and a historical arithmetic inference into original arm-specific analysis counts.", "application_exception": "Preserve the existing 60 participants only as a historical calculated value; do not recalculate it in this exercise.", "criterion": "Link the report of 240 participants and 4 arms to the verification level of the inferred 60 participants and the unverified original arm-specific counts.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Publish a flow diagram of allocation, follow-up, completion and analysis denominators by arm, and provide the actual denominator for each outcome in tables.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "A total randomized population of 240 participants and 4 arms is recorded. The 60 participants in each arm are an existing arithmetic inference in CAL01, not a verified original arm-specific allocation/analysis denominator.", "condition_status": "Partly verified", "status_reason": "The sources of the total number and historical calculation were distinguished, but actual flow by arm remains unverified.", "missingness": "Do not use 60 as the analysis n, completion n or adverse-event denominator.", "uncertainty": "Do not use 60 as the analysis n, completion n or adverse-event denominator.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Flow diagram of actual allocation, completion and analysis overall/by arm, distinguished from the historical calculation" }, { "item_id": "N17", "question_type": "Analysis population and missing data", "question": "Were the monotherapy-arm analysis count, ITT/PP and handling of dropouts verified?", "needed": "Completion/analysis/dropouts by arm, ITT/PP, missing data/imputation and analysis population", "role": "Required", "role_reason": "Required to avoid treating the reported total alone as verification of complete follow-up or an ITT analysis.", "application_exception": "Do not fill in missing analysis denominators or dropout counts with 0 or 60.", "criterion": "Link the verification scope of the monotherapy-arm denominators and missing-data handling to the results.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Report actual denominators and reasons for missing data by arm, and prespecify the main analysis of the assignment effect, imputation and sensitivity analyses.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Actual allocation, completion, analysis and dropout counts in the B12 arm are left blank. ITT/PP, missing data, imputation and the analysis population are also unverified.", "condition_status": "Unverified", "status_reason": "Direct material is unavailable to examine the analysis denominator and handling of missing data for the between-group outcome of interest.", "missingness": "Do not turn the total of 240 participants into the analysis n for the target effect.", "uncertainty": "Do not turn the total of 240 participants into the analysis n for the target effect.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Completion/analysis/dropouts by arm, ITT/PP, missing data/imputation and analysis population" }, { "item_id": "N18", "question_type": "Direct monotherapy-arm effect", "question": "Were the global cognition difference, CI and P for B12 alone versus control verified?", "needed": "Original monotherapy-arm between-group estimate for the main global cognition outcome, unit, timepoint, denominator, CI/P and original table", "role": "Required", "role_reason": "Required to avoid transferring combination-arm numbers or review wording to the original monotherapy-arm effect.", "application_exception": "The currently unverified direct values do not constitute a judgment of an effect of 0 or no effect.", "criterion": "Display an effect for the monotherapy contrast of interest only when its actual estimate is verified.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Publish the prespecified between-group global cognition difference, CI and denominator for the B12 monotherapy contrast on the same background.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The structured global cognition effect, CI and P for B12 versus control are left blank. A directly eligible monotherapy estimate was not verified.", "condition_status": "Unverified", "status_reason": "The current input lacks the between-group numbers of interest, so the magnitude and precision of improvement cannot be established.", "missingness": "Do not transfer d = 0.169, P = 0.024 to this contrast.", "uncertainty": "Do not transfer d = 0.169, P = 0.024 to this contrast.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original monotherapy-arm between-group estimate for the main global cognition outcome, unit, timepoint, denominator, CI/P and original table" }, { "item_id": "N19", "question_type": "Attribution of the positive combination-arm result", "question": "Which comparison do d = 0.169 and P = 0.024 refer to?", "needed": "Original abstract for the combination arm versus no treatment, effect definition/method of calculating d, timepoint and denominator", "role": "Required", "role_reason": "Required to avoid using the positive combination-arm result as the effect of B12 alone.", "application_exception": "Retain results that are not unfavorable as well, attributing them to the actual combination comparison.", "criterion": "Attribute the current positive numbers only to the actual combination contrast.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Prespecify combination and monotherapy contrasts separately, and provide each contrast's between-group estimate, denominator, CI and effect definition separately.", "current_reports": [ "S01" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The original abstract's d = 0.169, P = 0.024 are results for the folic acid+B12 combination arm versus no treatment. The method of calculating d and an applicable important-difference threshold are unverified.", "condition_status": "Partly verified", "status_reason": "The reported numbers and comparison are preserved, but they cannot be interpreted as the effect of B12 alone or as establishing clinical importance.", "missingness": "Do not reconstruct a monotherapy effect, CI or MCID from a P value.", "uncertainty": "Do not reconstruct a monotherapy effect, CI or MCID from a P value.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original abstract for the combination arm versus no treatment, effect definition/method of calculating d, timepoint and denominator" }, { "item_id": "N20", "question_type": "Conditional add-on effect", "question": "How is the favorable post hoc statement for combination versus folic acid preserved?", "needed": "Original C02 results, same background, estimate/CI/P and whether the contrast was prespecified", "role": "Required", "role_reason": "Required to consider the possibility of the same folic acid background without turning a conditional candidate into a confirmed comparison.", "application_exception": "Do not delete the favorable statement because it comes from a post hoc comparison, but do not promote it to a prespecified primary endpoint.", "criterion": "Record the conditional add-on candidate together with the currently unverified eligible numbers.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Prespecify the added B12 contrast on the same folic acid background, and disclose the main global cognition result, interval and handling of multiple comparisons.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "A post hoc statement favors the combination arm over the folic acid monotherapy arm. The C02 effect, CI, P, same folic acid background and prespecified endpoint hierarchy are unverified.", "condition_status": "Unverified", "status_reason": "The add-on effect candidate is preserved, but essential aspects of direct-result verification remain unresolved.", "missingness": "Do not transfer the d/P for C01 to the numbers for C02.", "uncertainty": "Do not transfer the d/P for C01 to the numbers for C02.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original C02 results, same background, estimate/CI/P and whether the contrast was prespecified" }, { "item_id": "N21", "question_type": "Model and printed post hoc method", "question": "Were the repeated-measures model and the printed Turkey distinguished from the actual analysis?", "needed": "Original analysis section, model/covariates for each contrast, post hoc method, multiple comparisons and main/sensitivity distinction", "role": "Required", "role_reason": "Required to avoid inferring a confirmed analysis for a particular contrast from a model category or post hoc label.", "application_exception": "Do not silently correct the original printed Turkey to Tukey.", "criterion": "Distinguish the reported ANOVA/mixed models from unverified contrast-specific plans.", "basis": "M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Prespecify the model, covariates, main/sensitivity analyses and handling of multiple comparisons for each contrast, and report whether the original printing was corrected.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The reported models are repeated-measures ANOVA or mixed-effects models. The publisher prints Turkey; the exact family of comparisons subject to adjustment, main analysis and contrast-specific models are unverified.", "condition_status": "Partly verified", "status_reason": "There are leads about the model and post hoc label, but the confirmed analysis for a particular main contrast cannot be reconstructed.", "missingness": "This does not justify inferred corrections or selection of favorable analyses after the fact.", "uncertainty": "This does not justify inferred corrections or selection of favorable analyses after the fact.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original analysis section, model/covariates for each contrast, post hoc method, multiple comparisons and main/sensitivity distinction" }, { "item_id": "N22", "question_type": "Variance and clinical importance", "question": "Were SD, SE, CI and an important difference in MCI verified?", "needed": "Original baseline/change/endpoint means, type of dispersion, CI and the applicable MCI/scale/between-group MCID", "role": "Required", "role_reason": "Required to avoid deciding precision and clinical meaning from significance, trial count or total n alone.", "application_exception": "Do not import another scale's MCID or a generic d = 0.2.", "criterion": "Link the verification level of dispersion, intervals and an important difference to the reasons interpretation is not possible.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M15 §15.3.1–15.3.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Establish evidence for an important difference appropriate to the scale, and report the actual between-group effect, CI and type of dispersion together with denominators.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The monotherapy arm's baseline/change/endpoint means, SD, SE, CI and an applicable between-group MCID in MCI are unverified. The score range and method of calculating d are also unverified.", "condition_status": "Unverified", "status_reason": "Without a direct effect, interval or importance threshold, adequacy and clinical meaning cannot be determined.", "missingness": "Do not generate new SD/SE/CI, minimum participant numbers, trial counts or durations.", "uncertainty": "Do not generate new SD/SE/CI, minimum participant numbers, trial counts or durations.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original baseline/change/endpoint means, type of dispersion, CI and the applicable MCI/scale/between-group MCID" }, { "item_id": "N23", "question_type": "Lead on a nonsignificant monotherapy result", "question": "Was the review's description of a nonsignificant B12 monotherapy result counted as an original result?", "needed": "The S13 citation concerning nonsignificant monotherapy and the original monotherapy table/CI and denominators", "role": "Required", "role_reason": "Required to preserve a contrary lead without promoting the review to verification of original monotherapy numbers.", "application_exception": "Do not turn nonsignificance into an effect of 0, equivalence or established absence of effect.", "criterion": "Distinguish a review lead from an interpretation of no difference that has not been verified in original material.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Disclose the complete original monotherapy comparison results, CIs and reporting selections to compare positive and nonsignificant results using the same criteria.", "current_reports": [ "S13" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "S13 preserves the account that the combination arm improved but B12 alone did not, as secondary (2nd) information. This does not turn the missing original monotherapy-arm numbers into a verified result showing no difference.", "condition_status": "Partly verified", "status_reason": "The unfavorable lead is retained, but verification of the original nonsignificant monotherapy result remains outstanding.", "missingness": "Do not count the review as an independent trial showing no B12 effect or as an original P value.", "uncertainty": "Do not count the review as an independent trial showing no B12 effect or as an original P value.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "The S13 citation concerning nonsignificant monotherapy and the original monotherapy table/CI and denominators" }, { "item_id": "N24", "question_type": "Directness of the older diabetic population", "question": "Can Kwok2017, with 271 participants, be used as an independent result for clinical MCI?", "needed": "Definition of the clinical MCI stratum, its separate main global cognition result and original denominator/interval", "role": "Required", "role_reason": "Required to avoid substituting a mixed nondemented diabetic population and CDR 0.5 for a confirmed MCI stratum.", "application_exception": "Do not exclude a study with an actual B12 monotherapy arm on ingredient grounds.", "criterion": "Use only the verified scope of direct comparisons in the whole cohort and a separately identified MCI stratum.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Prespecify the clinical MCI stratum and report its monotherapy comparison and main global score/CI separately.", "current_reports": [ "S04", "S18" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Kwok2017 concerns 271 nondemented older people with diabetes. An increase in global CDR and NTB z scores are distinct, and an eligible main result for the clinical MCI stratum could not be separated. Do not turn nonsignificance in the whole population into no monotherapy effect in MCI.", "condition_status": "Not met", "status_reason": "The currently verified overall population and endpoints do not satisfy the direct criteria for this narrow question about monotherapy and global cognition in clinical MCI.", "missingness": "There is no separate MCI estimate, and the proportion with CDR 0.5 alone does not establish the diagnosis.", "uncertainty": "There is no separate MCI estimate, and the proportion with CDR 0.5 alone does not establish the diagnosis.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Definition of the clinical MCI stratum, its separate main global cognition result and original denominator/interval" }, { "item_id": "N25", "question_type": "Combination treatment in MCI and 24 months", "question": "Does Kwok2020, with 279 participants and CDR-SOB at 24 months, provide a result for B12 alone?", "needed": "Composition of the methylcobalamin/folic acid arm, original CDR-SOB results at 24 months and a contrast differing only in B12", "role": "Required", "role_reason": "Required to avoid attributing a multiple-ingredient effect to B12 alone merely because the MCI population matches.", "application_exception": "Preserve the combination treatment's original result and duration without decomposing them into monotherapy-arm numbers.", "criterion": "Even within MCI, distinguish multiple active ingredients and a different primary endpoint.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Design a contrast differing only in B12 on the same background, and prespecify the effect of interest on the global scale.", "current_reports": [ "S05" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Kwok2020 reports CDR-SOB in 279 participants with MCI at 24 months. Methylcobalamin and folic acid both differ between arms, so this is not a B12 monotherapy effect. The current input contains no verified actual effect/CI values.", "condition_status": "Not met", "status_reason": "The actual contrast involves multiple active ingredients and cannot be used as this page's B12 monotherapy contrast for global cognition.", "missingness": "Do not transfer numbers for a different endpoint or timepoint to WAIS-RC at 6 months.", "uncertainty": "Do not transfer numbers for a different endpoint or timepoint to WAIS-RC at 6 months.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Composition of the methylcobalamin/folic acid arm, original CDR-SOB results at 24 months and a contrast differing only in B12" }, { "item_id": "N26", "question_type": "Deficiency, mixed cognitive status and an unfavorable domain result", "question": "In Eussen2006, what is the scope of the 195 participants and the memory result favoring placebo?", "needed": "Separate clinical MCI stratum/main global result, original memory-domain table and DOI identity", "role": "Required", "role_reason": "Required to distinguish biochemical deficiency, mixed cognitive status and domain results.", "application_exception": "An actual B12 monotherapy arm exists; do not exclude the study because it also has a combination arm.", "criterion": "Preserve the deficient population with mixed cognitive status and the domain result favoring placebo within their original scope.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Separate the monotherapy contrast in clinical MCI, and report global cognition and the memory domain in separate plans/results.", "current_reports": [ "S07" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Eussen2006 is a study of 195 older people in 3 arms with mild biochemical B12 deficiency. Baseline cognitive status is mixed, and a separate main global outcome for MCI is unverified. The memory-domain result favoring placebo is also preserved. The DOI metadata conflict remains unassigned.", "condition_status": "Not met", "status_reason": "The criterion of separating a direct main global cognition estimate in MCI was not met. The unfavorable domain result was not omitted.", "missingness": "Do not repurpose the memory domain as the global WAIS-RC effect or as no effect in MCI.", "uncertainty": "Do not repurpose the memory domain as the global WAIS-RC effect or as no effect in MCI.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Separate clinical MCI stratum/main global result, original memory-domain table and DOI identity" }, { "item_id": "N27", "question_type": "Mixed routes, two chemical forms and printed inconsistencies", "question": "Were the routes and printed dose/dropout inconsistencies in Zhou2023 distinguished?", "needed": "Dose unit, route/chemical form, flow diagram, dropout-rate table and corrections in the original Methods", "role": "Required", "role_reason": "Required to avoid turning injection followed by two oral chemical forms in broad cognitive impairment into oral monotherapy in MCI.", "application_exception": "Do not arbitrarily correct the printed 500 mg unit or dropout-rate inconsistencies recorded by the original review to another unit or value.", "criterion": "Link only the boundaries of the mixed regimen and the currently retained record of inconsistencies.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Compare units and dropout flow in the original tables/Methods, and separately design an oral single-chemical-form contrast in clinical MCI.", "current_reports": [ "S06" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Zhou2023 reports a regimen in 115 participants of intramuscular injection followed by oral cobamamide+methylcobalamin. The population was not verified as exclusively clinical MCI. The stored bibliographic record specifies the printed IM 500 mg and conflicting dropout rates, but the exact conflicting dropout-rate values are absent from the current stored summary.", "condition_status": "Conflicting information", "status_reason": "The original review's inconsistencies concerning unusual units/dropout rates were linked unchanged. They were not reverified against newly read clinical original material.", "missingness": "The direct criteria also do not match; do not correct the original values or transfer incidence from another formulation.", "uncertainty": "The direct criteria also do not match; do not correct the original values or transfer incidence from another formulation.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Dose unit, route/chemical form, flow diagram, dropout-rate table and corrections in the original Methods" }, { "item_id": "N28", "question_type": "Uncontrolled before-and-after results and inconsistent counts", "question": "In Jatoi2020, are the before-and-after MMSE responses in 202 participants a between-group effect?", "needed": "Control/allocation, original MMSE response table/participant counts and definition of the deficient population", "role": "Required", "role_reason": "Required to distinguish before-and-after improvement after correction of deficiency from efficacy versus placebo.", "application_exception": "Preserve inconsistent counts in the original abstract without reconstructing detailed subgroup counts absent from the current material.", "criterion": "Specify the limitations of uncontrolled before-and-after results and inconsistent participant counts.", "basis": "M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Use an appropriate control on the same background, and report the clinical MCI population and global-scale effect with denominators/intervals.", "current_reports": [ "S09" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Jatoi2020 observes 202 deficient patients before and after B12 correction. There is no randomized matched control, and the before-and-after MMSE responses are not an effect versus placebo. A retained record states that subgroup counts in the abstract are internally inconsistent.", "condition_status": "Conflicting information", "status_reason": "The inconsistent counts and limitations of the comparative design were preserved together. Response rates and subgroup counts absent from the current material were not inferred.", "missingness": "Do not turn before-and-after improvement into a direct between-group effect or universal efficacy regardless of deficiency status.", "uncertainty": "Do not turn before-and-after improvement into a direct between-group effect or universal efficacy regardless of deficiency status.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Control/allocation, original MMSE response table/participant counts and definition of the deficient population" }, { "item_id": "N29", "question_type": "VITACOG combination, imaging and the same family", "question": "Were the 271 participants and subsequent imaging reports from VITACOG counted as independent monotherapy replications?", "needed": "VITACOG registration/report family and linkage of the three active ingredients to original/subsequent endpoints", "role": "Required", "role_reason": "Required to avoid double-counting combined B vitamins and subsequent reports from the same trial as B12 monotherapy replications.", "application_exception": "Retain the original imaging and cognition reports without creating separate independent trial counts.", "criterion": "Distinguish the B12/folic acid/B6 combination contrast from imaging within the same trial family.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Link overlapping participants by trial family, and separately design/analyze the B12 monotherapy contrast and main global cognition outcome.", "current_reports": [ "S10" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "VITACOG is a combination trial in 271 participants with MCI using B12, folic acid and B6. Subsequent brain-atrophy, cognition and MRI/omega-3/PON1 reports are preserved within the same family and are not counted as independent B12 monotherapy replications.", "condition_status": "Not met", "status_reason": "Multiple active ingredients, different endpoints and reports from the same family do not satisfy the direct criteria for the narrow monotherapy effect.", "missingness": "Do not repurpose MRI brain atrophy as improvement in global cognition scores or prevention of dementia.", "uncertainty": "Do not repurpose MRI brain atrophy as improvement in global cognition scores or prevention of dementia.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "VITACOG registration/report family and linkage of the three active ingredients to original/subsequent endpoints" }, { "item_id": "N30", "question_type": "Alzheimer's disease and combination treatment", "question": "Was Chen's combination trial in Alzheimer's disease used as a monotherapy effect in MCI?", "needed": "Alzheimer's disease population, folic acid/B12 composition, original n/endpoints and a separate MCI contrast", "role": "Required", "role_reason": "Required to avoid extending material differing in both diagnosis and ingredients to a direct effect in MCI.", "application_exception": "If the original n is absent from the current material, do not fill it in with participant numbers from another study.", "criterion": "Preserve the AD/combination boundaries and unverified original numbers within their original scope.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Separately design a comparison in clinical MCI differing only in B12, and distinguish it from AD results.", "current_reports": [ "S17" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Chen's material concerns a population with diagnosed Alzheimer's disease and a folic acid+B12 combination intervention. The original participant count is unverified in the current input.", "condition_status": "Not met", "status_reason": "The direct criteria for both population and added active ingredients differ from this question.", "missingness": "Retain the original results, but do not transfer them as monotherapy efficacy or participant numbers in MCI.", "uncertainty": "Retain the original results, but do not transfer them as monotherapy efficacy or participant numbers in MCI.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Alzheimer's disease population, folic acid/B12 composition, original n/endpoints and a separate MCI contrast" }, { "item_id": "N31", "question_type": "Adjacent monotherapy trial and historical access failure", "question": "Were unverified original numbers from Dangour2015 used as current direct evidence?", "needed": "Original population, dose, denominator/global scale and the main result in the clinical MCI stratum", "role": "Required", "role_reason": "Required to distinguish a discovered RCT bibliographic record from an unobtained full text and unavailable population details.", "application_exception": "Do not label historical full-text access failure as a failure in this exercise, or turn failure to obtain material into absence of research.", "criterion": "Distinguish bibliographic discovery from unverified direct material.", "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Assess eligibility after obtaining original population/endpoint/separate-stratum material, and design a clinical MCI monotherapy contrast if needed.", "current_reports": [ "S08" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Dangour2015 is a verified RCT bibliographic lead. Historical full-text access failure is preserved, and the original participant count, dose and main result for the MCI stratum were not verified in the current input.", "condition_status": "Unverified", "status_reason": "Bibliographic existence is verified, but material establishing the population, endpoint or effect for this narrow question is unavailable.", "missingness": "Current web access has not been attempted, and no original numbers are newly filled in.", "uncertainty": "Current web access has not been attempted, and no original numbers are newly filled in.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original population, dose, denominator/global scale and the main result in the clinical MCI stratum" }, { "item_id": "N32", "question_type": "Healthy athletes and a recent lead", "question": "Was the 2026 cyclist study extrapolated to clinical MCI?", "needed": "Original population/results, whether clinical MCI was present and bibliographic identity", "role": "Required", "role_reason": "Required to avoid extending an effect in another population to MCI merely because it is a recent cognitive-performance study.", "application_exception": "Retain the bibliographic lead without generating an original n or effect size in this exercise.", "criterion": "Distinguish the amateur-cyclist title from the clinical MCI question.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Separately review/design the monotherapy comparison in clinical MCI, without pooling it with performance results in athletes.", "current_reports": [ "S19" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "S19 is a bibliographic lead for a 2026 randomized crossover trial in amateur cyclists. The population does not have clinical MCI, and the original n and effect values are currently unverified.", "condition_status": "Not met", "status_reason": "The verified population differs from the narrow clinical MCI criterion.", "missingness": "Do not derive directness or an original effect from recency or a crossover title.", "uncertainty": "Do not derive directness or an original effect from recency or a crossover title.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original population/results, whether clinical MCI was present and bibliographic identity" }, { "item_id": "N33", "question_type": "Reviews as maps and unverified identity", "question": "Were review averages or the 2025 lead counted as direct monotherapy estimates?", "needed": "Included-study tables, original identities and separate estimates for MCI/monotherapy/global outcomes in the reviews", "role": "Required", "role_reason": "Required to avoid promoting a broad B-vitamin/cognition review to a narrow MCI monotherapy effect.", "application_exception": "Preserve the reviews' negative/positive leads and access limitations without describing the search as complete.", "criterion": "Distinguish the actual mapping roles of S11/S12/S13/S20 from the unverified status of original values.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Link included studies and original contrasts by family, and separately organize only material meeting the same direct criteria.", "current_reports": [ "S11", "S12", "S13", "S20" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "S11 and S13 are secondary (2nd) maps to original material; S12 is a review bibliographic record whose full text was not historically obtained; S20 is a search lead for a 2025 review. The exact DOI/PMID and original material for S20 are unverified, and no pooled effect was applied to the narrow question.", "condition_status": "Unverified", "status_reason": "Material to verify an original direct monotherapy result or a separate estimate from an eligible review is currently unavailable.", "missingness": "Do not add review counts to included-trial counts or use a broad average as an efficacy value.", "uncertainty": "Do not add review counts to included-trial counts or use a broad average as an efficacy value.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Included-study tables, original identities and separate estimates for MCI/monotherapy/global outcomes in the reviews" }, { "item_id": "N34", "question_type": "Overlap of reports and trial families", "question": "Were the 21 reports counted as unique independent monotherapy trials?", "needed": "Relationships among Ma/registration/author abstracts, Kwok registration and the VITACOG follow-up family", "role": "Required", "role_reason": "Required to avoid double-counting abstracts, bibliographic records, registration, reviews or subsequent reports of the same Ma2019 study as independent replications.", "application_exception": "Retain provisional linkages/unverified status for families lacking sufficient identity material.", "criterion": "Link report-specific roles and family IDs, and leave the unconfirmed count of unique direct trials blank.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Link each report to a unique trial and its original contrast/timepoint to separate duplication before assessing replication.", "current_reports": [ "S01", "S02", "S03", "S04", "S10", "S18", "S21" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "For Ma2019, S01/S02/S03/S21 are the publisher abstract, bibliographic record, registration lead and duplicate author abstract for the same candidate. S04/S18 also have a linked registration. The 21 citation records were not counted as 21 independent trials.", "condition_status": "Partly verified", "status_reason": "Verified linkages within the same families were preserved, but no new count of eligible unique direct trials was established.", "missingness": "Do not count VITACOG follow-up reports/reviews as new independent B12 replications.", "uncertainty": "Do not count VITACOG follow-up reports/reviews as new independent B12 replications.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Relationships among Ma/registration/author abstracts, Kwok registration and the VITACOG follow-up family" }, { "item_id": "N35", "question_type": "Current scope and historical verdict", "question": "Were 0 directly eligible results distinguished from the existence of human research?", "needed": "Original evidence date, existence of human research/direct eligibility status, original grade/score and explanation of the historical calculation", "role": "Required", "role_reason": "Required to avoid turning unverified information in the current scope into worldwide absence of research or an effect of 0.", "application_exception": "Preserve the original no_human_study=false and stage-gate projection without rerunning the legacy calculator.", "criterion": "Distinguish the scope as of 2026-09-16 from the reading for conversion on 2026-10-05 and from the original verdict.", "basis": "M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "If the original search/eligibility record is updated, disclose the direct criteria for population, ingredient, outcome and duration, together with exclusion reasons.", "current_reports": [], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The original scope is dated 2026-09-16, and the existence of human trials=true, no_human_study=false and 0 verified eligible results are preserved together. The original grade ?, score left blank and unscored axes are retained; no new search, calculation or reassessment was performed in this exercise.", "condition_status": "Met", "status_reason": "The original verdict, limited scope and explanation of the historical calculation were linked unchanged. This does not mean the direct efficacy criteria were met.", "missingness": "The legacy calculator's inability to validate the original factual profile is also preserved; no efficacy value of 0 is created.", "uncertainty": "The legacy calculator's inability to validate the original factual profile is also preserved; no efficacy value of 0 is created.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original evidence date, existence of human research/direct eligibility status, original grade/score and explanation of the historical calculation" }, { "item_id": "N36", "question_type": "Extension to clinical events and surrogate measures", "question": "Does the global score also answer questions about conversion to dementia, daily functioning and brain atrophy?", "needed": "Separate direct results and interpretive scope for events/daily functioning and the global scale", "role": "Supplementary; required for extending the claim to clinical events", "role_reason": "Considered to distinguish the cognitive-performance objective from separate event/functional and biochemical outcomes.", "application_exception": "Do not unconditionally require a dementia-conversion trial for the global-score question.", "criterion": "Do not substitute global FSIQ, domain tests, brain volume, blood B12/homocysteine or dementia for one another.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "When separately planning claims about conversion to dementia, daily functioning or quality of life, design direct measurements of the corresponding events/functions.", "current_reports": [ "S10" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Whether FSIQ improves is a cognitive-performance question in its own right. The current material does not also establish dementia prevention, improved daily functioning or biochemical/brain-volume changes.", "condition_status": "Not applicable", "status_reason": "A trial of dementia events is not imposed as a prerequisite for this narrow global-score assessment. That extended claim is unverified.", "missingness": "No judgment of absence of events or absence of an effect on events is made either.", "uncertainty": "No judgment of absence of events or absence of an effect on events is made either.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Separate direct results and interpretive scope for events/daily functioning and the global scale" }, { "item_id": "N37", "question_type": "Core trial adverse events and denominators", "question": "Were AE, SAE, discontinuations, deaths and observation periods by arm verified?", "needed": "Definitions, collection, participant/event counts, denominators and follow-up periods for AE/SAE and discontinuations/deaths by arm", "role": "Supplementary; required for safety interpretation", "role_reason": "Required to avoid turning unreported adverse events into 0 events or established safety.", "application_exception": "Retain gaps in harms data despite unverified efficacy data, and limit the nonreporting statement to the original abstract's scope.", "criterion": "Distinguish the core candidate's actual harms counts from the unverified scope.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Define and systematically collect adverse events, and report exposed participants, participant/event counts, duration and discontinuations by arm separately from efficacy denominators.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "AE, SAE, discontinuations due to adverse events, deaths and safety follow-up by arm in Ma2019 are left blank; the retained structure records them as not reported in the accessed abstract. Actual safety denominators are also unverified.", "condition_status": "Unverified", "status_reason": "The current stored summary's statement of nonreporting within the abstract was read. Neither 0 events in the entire original paper nor nonreporting in a full text read in this exercise was established.", "missingness": "Do not use the existing inference of 60 participants per arm as a safety denominator.", "uncertainty": "Do not use the existing inference of 60 participants per arm as a safety denominator.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Definitions, collection, participant/event counts, denominators and follow-up periods for AE/SAE and discontinuations/deaths by arm" }, { "item_id": "N38", "question_type": "UL and nutrition/medication context", "question": "Was the absence of an established UL interpreted as unlimited safety or efficacy in MCI?", "needed": "Original ODS context for UL/medications and safety exposure data by population/formulation", "role": "Supplementary", "role_reason": "Considered to avoid extending nutritional information to clinical efficacy or a guarantee of overall safety.", "application_exception": "Distinguish historical descriptions of official documents from direct reading in this exercise.", "criterion": "Retain the limited role of the absence of an established UL and of the metformin/gastric-acid-inhibitor context.", "basis": "M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Design observations of long-term/high-dose exposure and safety by population/formulation, and track concomitant medications and B12 status.", "current_reports": [ "S14" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "S14 records that the absence of an established UL does not prove unlimited safety or MCI efficacy. The context in which gastric acid inhibitors and metformin affect B12 exposure/status is also preserved.", "condition_status": "Partly verified", "status_reason": "The official context is recorded in the retained material, but individual exposure and long-term safety in the core candidate are unverified.", "missingness": "The ODS original was not read in this exercise, and no personal dosing or medication-discontinuation instructions are created.", "uncertainty": "The ODS original was not read in this exercise, and no personal dosing or medication-discontinuation instructions are created.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original ODS context for UL/medications and safety exposure data by population/formulation" }, { "item_id": "N39", "question_type": "Cobalt warning and chemical-form scope", "question": "Was the MHRA warning transferred to the incidence for another B12 chemical form?", "needed": "Original hydroxocobalamin/cyanocobalamin warning and exposure/population/event denominators", "role": "Supplementary", "role_reason": "Required to distinguish the warning's actual chemical-form scope from event incidence.", "application_exception": "General cobalt-allergy prevalence is not an adverse-event rate during B12 treatment.", "criterion": "Preserve the sensitivity warning only for the specified chemical forms, without estimating comparative risks for other chemical forms.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Develop appropriate observational material tracking chemical-form-specific exposure, sensitivity-event definitions and denominators.", "current_reports": [ "S15" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "S15 provides the cobalt-sensitivity warning context for hydroxocobalamin and cyanocobalamin. Do not use general cobalt-allergy prevalence as a treatment AE rate or transfer it to incidence for methyl/adenosyl formulations.", "condition_status": "Partly verified", "status_reason": "The scope to which the warning applies is preserved, but the core monotherapy arm's chemical form and comparative incidence are unverified.", "missingness": "The regulatory original was not opened in this exercise, and no quantitative risk for all B12 is created.", "uncertainty": "The regulatory original was not opened in this exercise, and no quantitative risk for all B12 is created.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original hydroxocobalamin/cyanocobalamin warning and exposure/population/event denominators" }, { "item_id": "N40", "question_type": "Injection labeling and Leber/hypokalemia", "question": "Was cyanocobalamin injection labeling repurposed as risk in oral treatment for MCI?", "needed": "The actual injectable product's labeling warnings about Leber disease and hypokalemia during intensive treatment of severe anemia, and direct oral safety data", "role": "Supplementary", "role_reason": "Required to avoid transferring labeling with a different route, chemical form and intensive-treatment population to incidence in an oral trial.", "application_exception": "Retain the labeling language without interpreting it as incidence for another chemical form or oral treatment in MCI.", "criterion": "Distinguish the population/route in injection labeling from the current oral question.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Separately observe safety counts in the oral MCI population by formulation, exposure and medical history, distinguishing them from intensive injectable-treatment data.", "current_reports": [ "S16" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "S16 concerns Leber optic atrophy and hypokalemia during intensive treatment of severe megaloblastic anemia in cyanocobalamin injection labeling. It is not incidence data for oral treatment in MCI.", "condition_status": "Partly verified", "status_reason": "The labeling has a narrowly attributable scope, but event counts/risks for oral monotherapy in MCI are unverified.", "missingness": "The DailyMed original was not read in this exercise, and the labeling scope is not expanded.", "uncertainty": "The DailyMed original was not read in this exercise, and the labeling scope is not expanded.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "The actual injectable product's labeling warnings about Leber disease and hypokalemia during intensive treatment of severe anemia, and direct oral safety data" }, { "item_id": "N41", "question_type": "Long-term safety and vulnerable populations", "question": "Were harms from high doses or in special populations beyond 6 months verified?", "needed": "Exposure and follow-up for long-term/high-dose use, pregnancy/lactation/children and liver/kidney status", "role": "Supplementary; required for the corresponding extension of safety claims", "role_reason": "Required to avoid extending material from a limited duration/population to overall safety.", "application_exception": "Do not require every rare-harm study for the current cognitive-score question.", "criterion": "Distinguish the direct observation period from the scope of unverified special populations.", "basis": "M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M19 §19.1.2–19.2.4; internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Systematically collect population-specific harms in exposure registries/observational material with sufficient follow-up, and distinguish rare-event reports from incidence.", "current_reports": [ "S01", "S03" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Safety of long-term high doses and in pregnancy, lactation, children, liver disease and kidney disease is unverified in the retained structure for the core candidate. Do not extend the reported 6 months to safety in all special populations.", "condition_status": "Unverified", "status_reason": "Population-specific and duration-specific safety material and denominators were not verified.", "missingness": "Do not turn unverified information into absence of risk or a quantitative harmful effect.", "uncertainty": "Do not turn unverified information into absence of risk or a quantitative harmful effect.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Exposure and follow-up for long-term/high-dose use, pregnancy/lactation/children and liver/kidney status" }, { "item_id": "N42", "question_type": "Funding, product provision and independence", "question": "Were unverified Ma funding and disclosures in adjacent trials/reviews distinguished?", "needed": "Original disclosures of Ma funding, product provision, employment/patents/interests and sponsor roles", "role": "Supplementary; required for a claim of independence", "role_reason": "Required to avoid transferring disclosures from adjacent material as verification of the core trial's funding or independence.", "application_exception": "Do not automatically discard results because industry-related support exists, or treat a declaration of no sponsor role as establishing absence of bias.", "criterion": "Distinguish unverified core material from the actual scope of VITACOG/S13 disclosures.", "basis": "Chamgap's own criteria for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "Transparently report the core trial's funding, product provision and author relationships, and separately assess replication criteria for unique trials.", "current_reports": [ "S01", "S03", "S10", "S13" ], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "Ma funding, product provision, author employment/patents/interests and sponsor roles are unverified. VITACOG's public/charitable and Meda/Recip support and declaration of no sponsor role, and S13's unrestricted Pure Encapsulations donation and author consultancy disclosure, are attributed only to their respective material.", "condition_status": "Partly verified", "status_reason": "Disclosures from some adjacent material are preserved, but verification of the core monotherapy trial's independence remains outstanding.", "missingness": "Do not transfer another source's disclosures to Ma or create a new independence score.", "uncertainty": "Do not transfer another source's disclosures to Ma or create a new independence score.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original disclosures of Ma funding, product provision, employment/patents/interests and sponsor roles" }, { "item_id": "N43", "question_type": "Material type, reading and access dates", "question": "Was summary reading separated from historical/current access for the 21 sources?", "needed": "Bibliographic/original URLs by material type, historical access level, access date and exact locations actually read in this exercise", "role": "Required", "role_reason": "Required to avoid retrospectively treating the prior manuscript's reading level and original review date as successful access/full-text reading in this exercise.", "application_exception": "If there is no actual access-date field, leave it blank and do not substitute verified_date for the access date.", "criterion": "Record reading of the current stored summaries, external access not attempted/material not read, and historical descriptions separately.", "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design", "condition_origin": "Individual internally designed criteria/model review with the retained case known. This is not clinical preregistration or independent methodological certification.", "proposed_research": "When direct material is subsequently obtained, record type, acquisition/access/reading/date and exact location as separate events, and review linked rows again.", "current_reports": [], "existence": "The retained statements/values in the currently linked stored summaries exist. This does not verify current external existence or efficacy.", "acquired_read": "Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise.", "observation": "The identities, summaries and flag_summary fields of the 21 citations were read in the current stored summaries. Publisher/author abstracts, bibliographic/registry failures, historical full texts/reviews and official contexts are each historical reports. Individual access-date fields are absent and remain blank; the original review date of 2026-09-16 is separate.", "condition_status": "Met", "status_reason": "Reading the current local stored summaries was separated by material type from external access not attempted/material not read in this exercise.", "missingness": "The complete original papers, protocols/SAPs and current publication/public-availability status were not newly verified.", "uncertainty": "The complete original papers, protocols/SAPs and current publication/public-availability status were not newly verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Bibliographic/original URLs by material type, historical access level, access date and exact locations actually read in this exercise" } ], "reports": [ { "report_id": "S01", "title": "Ma F et al. Effects of Folic Acid and Vitamin B12, Alone and in Combination… Curr Alzheimer Res. 2019;16(7):622–632.", "url": "https://www.eurekaselect.com/article/99971", "report_type": "Original publisher abstract and core 4-arm candidate", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-MA2019", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This is a candidate MCI trial with 240 participants, 4 arms and 6 months of treatment. WAIS-RC FSIQ is preserved as the page's review measure, but the prespecified primary endpoint and direct monotherapy-arm estimate are unverified. d = 0.169, P = 0.024 refer to the folic acid+B12 combination arm versus no treatment; the post hoc combination-versus-folic-acid statement is a candidate for added B12 if the same background is verified.", "result_level": "Original publisher abstract and core 4-arm candidate; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Paper abstract", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S01-M1", "url": "https://www.eurekaselect.com/article/99971", "parent_url": "https://www.eurekaselect.com/article/99971" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S01-M2", "url": null, "parent_url": "https://www.eurekaselect.com/article/99971" } ], "links": [ { "label": "Source", "url": "https://www.eurekaselect.com/article/99971" } ] }, { "report_id": "S02", "title": "Ma2019 PubMed bibliographic record", "url": "https://pubmed.ncbi.nlm.nih.gov/31345146/", "report_type": "Bibliographic record for the same Ma2019 study", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-MA2019", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This is a bibliographic lead for PMID 31345146. The citation's one_line is an empty string; do not invent a direct result summary in this record itself. Link its identity to other stored Ma2019 summaries without promoting it to verification of the full text or monotherapy numbers.", "result_level": "Bibliographic record for the same Ma2019 study; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full bibliographic web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S02-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/31345146/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/31345146/" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S02-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/31345146/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/31345146/" } ] }, { "report_id": "S03", "title": "ChiCTR-ROC-16008305 registry access attempt", "url": "https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-ROC-16008305", "report_type": "Registration-access lead for the core candidate", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-MA2019", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This is a registration lead for ChiCTR-ROC-16008305 with a historical record of inaccessible registration. The original registration date, original/changed endpoints and SAP are unverified. It is not a newly recorded current access failure and does not establish nonregistration or selective reporting.", "result_level": "Registration-access lead for the core candidate; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full registration web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S03-M1", "url": "https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-ROC-16008305", "parent_url": "https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-ROC-16008305" }, { "material_type": "Full protocol and statistical analysis plan", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S03-M2", "url": null, "parent_url": "https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-ROC-16008305" } ], "links": [ { "label": "Source", "url": "https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-ROC-16008305" } ] }, { "report_id": "S04", "title": "Kwok T et al. A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Clin Nutr. 2017;36(6):1509–1515.", "url": "https://pubmed.ncbi.nlm.nih.gov/27823800/", "report_type": "Actual monotherapy trial in a mixed diabetic population", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-KWOK2017", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "The population comprises 271 nondemented older people with diabetes. An increase in global CDR and NTB z scores are distinct. Do not transfer nonsignificance in the whole population to an established absence of a monotherapy effect in clinical MCI; the separate main MCI result is unverified.", "result_level": "Actual monotherapy trial in a mixed diabetic population; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full bibliographic web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S04-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/27823800/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/27823800/" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S04-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/27823800/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/27823800/" } ] }, { "report_id": "S05", "title": "Kwok T et al. A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients. Clin Nutr. 2020;39(8):2399–2405.", "url": "https://research.cuhk.edu.hk/en/publications/a-randomized-placebo-controlled-trial-of-using-b-vitamins-to-prev-2/", "report_type": "B12/folic acid combination trial in MCI", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-KWOK2020", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This concerns a methylcobalamin+folic acid combination comparison in 279 participants with MCI and CDR-SOB at 24 months. The original effect/CI values are currently unverified and are not decomposed into a B12 monotherapy effect.", "result_level": "B12/folic acid combination trial in MCI; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Paper abstract", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S05-M1", "url": "https://research.cuhk.edu.hk/en/publications/a-randomized-placebo-controlled-trial-of-using-b-vitamins-to-prev-2/", "parent_url": "https://research.cuhk.edu.hk/en/publications/a-randomized-placebo-controlled-trial-of-using-b-vitamins-to-prev-2/" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S05-M2", "url": null, "parent_url": "https://research.cuhk.edu.hk/en/publications/a-randomized-placebo-controlled-trial-of-using-b-vitamins-to-prev-2/" } ], "links": [ { "label": "Source", "url": "https://research.cuhk.edu.hk/en/publications/a-randomized-placebo-controlled-trial-of-using-b-vitamins-to-prev-2/" } ] }, { "report_id": "S06", "title": "Zhou et al. Vitamin B12 supplementation improves cognitive function in middle aged and elderly patients with cognitive impairment. Nutr Hosp. 2023;40(4).", "url": "https://scielo.isciii.es/scielo.php?pid=S0212-16112023000500007&script=sci_arttext", "report_type": "Adjacent report with mixed routes, two chemical forms and printed inconsistencies", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-ZHOU2023", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This reports intramuscular injection followed by oral cobamamide+methylcobalamin in a broad cognitively impaired population of 115 participants. Preserve the printed IM 500 mg and dropout-rate conflict without generating competing values or corrected units absent from the current material.", "result_level": "Adjacent report with mixed routes, two chemical forms and printed inconsistencies; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S06-M1", "url": "https://scielo.isciii.es/scielo.php?pid=S0212-16112023000500007&script=sci_arttext", "parent_url": "https://scielo.isciii.es/scielo.php?pid=S0212-16112023000500007&script=sci_arttext" } ], "links": [ { "label": "Source", "url": "https://scielo.isciii.es/scielo.php?pid=S0212-16112023000500007&script=sci_arttext" } ] }, { "report_id": "S07", "title": "Eussen SJ et al. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency. Am J Clin Nutr. 2006;84:361–370.", "url": "https://www.researchgate.net/publication/6891033_Effect_of_oral_vitamin_B-12_with_or_without_folic_acid_on_cognitive_function_in_older_people_with_mild_vitamin_B-12_deficiency_A_randomized_placebo-controlled_trial", "report_type": "Trial in deficiency with mixed cognitive status, including an actual monotherapy arm", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-EUSSEN2006", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This is a trial of 195 older people in 3 arms with mild biochemical B12 deficiency. The actual B12 monotherapy arm is acknowledged, but a separate main global outcome for clinical MCI is unverified. The memory-domain result favoring placebo and the unassigned DOI metadata conflict are both preserved.", "result_level": "Trial in deficiency with mixed cognitive status, including an actual monotherapy arm; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S07-M1", "url": "https://www.researchgate.net/publication/6891033_Effect_of_oral_vitamin_B-12_with_or_without_folic_acid_on_cognitive_function_in_older_people_with_mild_vitamin_B-12_deficiency_A_randomized_placebo-controlled_trial", "parent_url": "https://www.researchgate.net/publication/6891033_Effect_of_oral_vitamin_B-12_with_or_without_folic_acid_on_cognitive_function_in_older_people_with_mild_vitamin_B-12_deficiency_A_randomized_placebo-controlled_trial" } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/6891033_Effect_of_oral_vitamin_B-12_with_or_without_folic_acid_on_cognitive_function_in_older_people_with_mild_vitamin_B-12_deficiency_A_randomized_placebo-controlled_trial" } ] }, { "report_id": "S08", "title": "Dangour AD et al. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial. Am J Clin Nutr. 2015;102(3):639–647.", "url": "https://pubmed.ncbi.nlm.nih.gov/26135351/", "report_type": "Bibliographic lead and historical failure to access the original full text", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-DANGOUR2015", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This is a verified RCT bibliographic lead with historical full-text access failure. The original n, dose and main outcome for the clinical MCI stratum are currently unverified; do not turn this into an access/reading failure in this exercise.", "result_level": "Bibliographic lead and historical failure to access the original full text; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full bibliographic web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S08-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/26135351/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/26135351/" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S08-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/26135351/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/26135351/" } ] }, { "report_id": "S09", "title": "Jatoi S et al. Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia. Cureus. 2020;12(2):e6976.", "url": "https://pubmed.ncbi.nlm.nih.gov/32206454/", "report_type": "Uncontrolled correction of deficiency and inconsistent abstract counts", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-JATOI2020", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This observes 202 deficient patients with MMSE before and after B12 correction without a control. Preserve the recorded internal inconsistency in the abstract's subgroup counts without reconstructing detailed counts or response rates absent from the current material.", "result_level": "Uncontrolled correction of deficiency and inconsistent abstract counts; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full bibliographic web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S09-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/32206454/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/32206454/" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S09-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/32206454/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/32206454/" } ] }, { "report_id": "S10", "title": "Smith AD et al. Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS One. 2010;5:e12244.", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244", "report_type": "Combined B vitamins in MCI and follow-up context from the same trial", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-VITACOG", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This is the VITACOG family of a trial in 271 participants with MCI using a folic acid+B12+B6 combination. Subsequent brain-atrophy, cognition and MRI/omega-3/PON1 reports are linked to the same trial family. Public/charitable and Meda/Recip support and the declaration of no sponsor role are attributed only to that material.", "result_level": "Combined B vitamins in MCI and follow-up context from the same trial; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S10-M1", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244", "parent_url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244" } ], "links": [ { "label": "Source", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244" } ] }, { "report_id": "S11", "title": "Lauer AA et al. Mechanistic Link between Vitamin B12 and Alzheimer’s Disease. Biomolecules. 2022;12:129.", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8774227/", "report_type": "Secondary (2nd) review and map for verifying doses in original material", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "REVIEW-LAUER2022", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "B12 25 µg and folic acid 800 µg are preserved as secondary (2nd) dose leads and are not used as established original monotherapy-arm doses in Ma. No pooled estimate was applied to this question.", "result_level": "Secondary (2nd) review and map for verifying doses in original material; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full review article text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S11-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8774227/", "parent_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8774227/" } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8774227/" } ] }, { "report_id": "S12", "title": "Markun S et al. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue. Nutrients. 2021;13:923.", "url": "https://www.mdpi.com/2072-6643/13/3/923", "report_type": "Bibliographic record for a broad cognition review whose full text was not historically obtained", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "REVIEW-MARKUN2021", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "The broad B12/B-complex cognition review serves as a search map. It is not a direct MCI monotherapy estimate; do not label historical nonacquisition of the original text as a failure in this exercise.", "result_level": "Bibliographic record for a broad cognition review whose full text was not historically obtained; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full bibliographic/search web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S12-M1", "url": "https://www.mdpi.com/2072-6643/13/3/923", "parent_url": "https://www.mdpi.com/2072-6643/13/3/923" }, { "material_type": "Full review article text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S12-M2", "url": null, "parent_url": "https://www.mdpi.com/2072-6643/13/3/923" } ], "links": [ { "label": "Source", "url": "https://www.mdpi.com/2072-6643/13/3/923" } ] }, { "report_id": "S13", "title": "Elgar K. Vitamin B12: A Review of Clinical Use and Efficacy. Nutritional Medicine Journal. 2022;1(3):9–25.", "url": "https://www.nmi.health/vitamin-b12-a-review-of-clinical-use-and-efficacy/", "report_type": "Secondary (2nd) contrary lead and disclosure context", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "REVIEW-ELGAR2022", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "The account that the combination arm improved but B12 alone did not is a secondary (2nd) lead; it does not turn missing original values into a verified absence of effect. The unrestricted Pure Encapsulations donation and author consultancy disclosure are attributed to that review. Clinical safety recommendations are not reused.", "result_level": "Secondary (2nd) contrary lead and disclosure context; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full review article text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S13-M1", "url": "https://www.nmi.health/vitamin-b12-a-review-of-clinical-use-and-efficacy/", "parent_url": "https://www.nmi.health/vitamin-b12-a-review-of-clinical-use-and-efficacy/" } ], "links": [ { "label": "Source", "url": "https://www.nmi.health/vitamin-b12-a-review-of-clinical-use-and-efficacy/" } ] }, { "report_id": "S14", "title": "NIH Office of Dietary Supplements. Vitamin B12: Health Professional Fact Sheet.", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/", "report_type": "Official nutrition/safety context", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "OFFICIAL-ODS", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "The absence of an established UL does not prove unlimited safety or MCI efficacy. Do not transfer the context of metformin/gastric acid inhibitors and B12 exposure/status to actual concomitant use or risk rates in Ma.", "result_level": "Official nutrition/safety context; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S14-M1", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/", "parent_url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" } ], "links": [ { "label": "Source", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" } ] }, { "report_id": "S15", "title": "MHRA. Vitamin B12 (hydroxocobalamin, cyanocobalamin): known cobalt allergy and sensitivity reactions. 18 December 2023.", "url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions", "report_type": "Regulatory context for chemical-form-specific cobalt sensitivity", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "OFFICIAL-MHRA", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "Maintain the scope of the hydroxocobalamin/cyanocobalamin warning. General cobalt-allergy prevalence is not a B12 AE rate and is not transferred to incidence for methyl/adenosyl formulations.", "result_level": "Regulatory context for chemical-form-specific cobalt sensitivity; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S15-M1", "url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions", "parent_url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions" } ], "links": [ { "label": "Source", "url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions" } ] }, { "report_id": "S16", "title": "DailyMed. CYANOCOBALAMIN injection labeling.", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6", "report_type": "Cyanocobalamin injectable-product labeling", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "OFFICIAL-DMLABEL", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "Warnings about Leber optic atrophy and hypokalemia during intensive treatment of severe megaloblastic anemia concern injectable-product labeling. They are not adverse-event incidence for oral treatment in MCI.", "result_level": "Cyanocobalamin injectable-product labeling; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S16-M1", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6", "parent_url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6" } ], "links": [ { "label": "Source", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6" } ] }, { "report_id": "S17", "title": "Chen et al. Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer’s Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial.", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12280771/", "report_type": "Original report of combination treatment in AD", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-CHENAD2021", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This concerns a population with diagnosed Alzheimer's disease and a folic acid+B12 combination intervention. Do not combine it with the clinical MCI monotherapy contrast, and retain the currently unverified original n.", "result_level": "Original report of combination treatment in AD; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S17-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12280771/", "parent_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12280771/" } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12280771/" } ] }, { "report_id": "S18", "title": "NCT02457507 registry landing page", "url": "https://clinicaltrials.gov/study/NCT02457507", "report_type": "Registry landing-page lead for the same Kwok2017 study", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-KWOK2017", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "NCT02457507 is a registration lead for the family linked to S04. It is not registration material that independently verified the actual endpoint hierarchy, and it is not counted as a new trial.", "result_level": "Registry landing-page lead for the same Kwok2017 study; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full registration web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S18-M1", "url": "https://clinicaltrials.gov/study/NCT02457507", "parent_url": "https://clinicaltrials.gov/study/NCT02457507" }, { "material_type": "Full protocol and statistical analysis plan", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S18-M2", "url": null, "parent_url": "https://clinicaltrials.gov/study/NCT02457507" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT02457507" } ] }, { "report_id": "S19", "title": "Martínez-Noguera et al. Short-Term Methylcobalamin Supplementation Is Associated with Changes in Anaerobic and Cognitive Performance in Amateur Cyclists: A Randomized Crossover Trial. Nutraceuticals. 2026;6(2):35.", "url": "https://www.mdpi.com/1661-3821/6/2/35", "report_type": "Bibliographic lead from 2026 in an athlete population", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-CYCLISTS2026", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "The population comprises amateur cyclists, not people with clinical MCI. Do not establish an original n or effect size from the current material or extrapolate this recent cognitive-performance lead to direct efficacy.", "result_level": "Bibliographic lead from 2026 in an athlete population; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full bibliographic web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S19-M1", "url": "https://www.mdpi.com/1661-3821/6/2/35", "parent_url": "https://www.mdpi.com/1661-3821/6/2/35" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S19-M2", "url": null, "parent_url": "https://www.mdpi.com/1661-3821/6/2/35" } ], "links": [ { "label": "Source", "url": "https://www.mdpi.com/1661-3821/6/2/35" } ] }, { "report_id": "S20", "title": "Berg J et al. Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis. 2025.", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=%22Efficacy+of+B+Vitamin+Supplementation+on+Global+Cognitive+Function%22", "report_type": "Review search lead with unverified exact identity", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "REVIEW-BERG2025", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "This is a search lead for a 2025 review; its exact DOI/PMID and original material are unverified. It was not used as a pooled effect or an independent trial count.", "result_level": "Review search lead with unverified exact identity; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full bibliographic/search web document", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S20-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=%22Efficacy+of+B+Vitamin+Supplementation+on+Global+Cognitive+Function%22", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/?term=%22Efficacy+of+B+Vitamin+Supplementation+on+Global+Cognitive+Function%22" }, { "material_type": "Full review article text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S20-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/?term=%22Efficacy+of+B+Vitamin+Supplementation+on+Global+Cognitive+Function%22" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=%22Efficacy+of+B+Vitamin+Supplementation+on+Global+Cognitive+Function%22" } ] }, { "report_id": "S21", "title": "Ma2019 author abstract on ResearchGate", "url": "https://www.researchgate.net/publication/334731884_Effects_Of_Folic_Acid_And_Vitamin_B_12_Alone_and_in_Combination_on_Cognitive_Function_and_inflammatory_Factors_in_the_Elderly_with_Mild_Cognitive_Impairment_A_Single-Blind_Experimental_Design", "report_type": "Duplicate author abstract for the same Ma2019 study", "existence": "This references stored bibliographic information and existing records; no current external response was checked.", "acquired_read": "The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise.", "study_family": "TF-MA2019", "independent_replication": "This record concerns material identity and the scope of results. The same paper, registration, author abstract or review is not counted as a unique independent direct trial.", "observed_result": "The author abstract on ResearchGate duplicates Ma2019 material and is not a separate trial. Do not infer missing monotherapy-arm numbers or acquisition of the full text.", "result_level": "Duplicate author abstract for the same Ma2019 study; retained scope from the original review dated 2026-09-16, not direct reading of clinical original material in this exercise.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Paper abstract", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. This is the currently retained entry URL for the material, not access or acquisition of the full text in this exercise. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S21-M1", "url": "https://www.researchgate.net/publication/334731884_Effects_Of_Folic_Acid_And_Vitamin_B_12_Alone_and_in_Combination_on_Cognitive_Function_and_inflammatory_Factors_in_the_Elderly_with_Mild_Cognitive_Impairment_A_Single-Blind_Experimental_Design", "parent_url": "https://www.researchgate.net/publication/334731884_Effects_Of_Folic_Acid_And_Vitamin_B_12_Alone_and_in_Combination_on_Cognitive_Function_and_inflammatory_Factors_in_the_Elderly_with_Mild_Cognitive_Impairment_A_Single-Blind_Experimental_Design" }, { "material_type": "Full paper text", "public_status": "Currently unverified (no external lookup)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Distinguish the local stored summaries and historical descriptions from external material types not read in this exercise. The direct URL for the full text/protocol is unverified. Do not promote a bibliographic URL to a full-text download link. It does not mean external original material was accessed, acquired or read in this exercise. The stored manuscript and external original material are distinct.", "material_id": "S21-M2", "url": null, "parent_url": "https://www.researchgate.net/publication/334731884_Effects_Of_Folic_Acid_And_Vitamin_B_12_Alone_and_in_Combination_on_Cognitive_Function_and_inflammatory_Factors_in_the_Elderly_with_Mild_Cognitive_Impairment_A_Single-Blind_Experimental_Design" } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/334731884_Effects_Of_Folic_Acid_And_Vitamin_B_12_Alone_and_in_Combination_on_Cognitive_Function_and_inflammatory_Factors_in_the_Elderly_with_Mild_Cognitive_Impairment_A_Single-Blind_Experimental_Design" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations in the intervention.", "review_level": "The actual retained copy/SHA and the methodological principles used at the time for 1585 were reused as historical material. This exercise did not newly read full methodological texts, perform an official method or provide clinical certification." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported.", "review_level": "The actual retained copy/SHA and the methodological principles used at the time for 1585 were reused as historical material. This exercise did not newly read full methodological texts, perform an official method or provide clinical certification." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.", "review_level": "The actual retained copy/SHA and the methodological principles used at the time for 1585 were reused as historical material. This exercise did not newly read full methodological texts, perform an official method or provide clinical certification." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "The actual retained copy/SHA and the methodological principles used at the time for 1585 were reused as historical material. This exercise did not newly read full methodological texts, perform an official method or provide clinical certification." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.", "review_level": "The actual retained copy/SHA and the methodological principles used at the time for 1585 were reused as historical material. This exercise did not newly read full methodological texts, perform an official method or provide clinical certification." } ], "status_dictionary": { "Met": "The relevant criterion within the question/retained scope was verified. This does not establish efficacy.", "Partly verified": "Some records are verified, while gaps in the relevant direct criteria/material remain.", "Unverified": "The required direct values/criteria were not verified within the current scope.", "Not met": "The population/ingredient/endpoint in the currently verified material does not match the selected direct criteria.", "Conflicting information": "A printing/counting conflict within the same material is explicitly recorded in the original retained record. It was not independently reverified against the original source in this exercise.", "Not applicable": "There is a reason not to impose the criterion on the narrow question.", "Not read": "The relevant external material was not actually read in this exercise." }, "study_overlap": { "state": "These are the report linkages in the stored manuscript. TF-MA2019 (S01, S02, S03, S21): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-KWOK2017 (S04, S18): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-KWOK2020 (S05): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-ZHOU2023 (S06): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-EUSSEN2006 (S07): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-DANGOUR2015 (S08): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-JATOI2020 (S09): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-VITACOG (S10): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-LAUER2022 (S11): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-MARKUN2021 (S12): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-ELGAR2022 (S13): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / OFFICIAL-ODS (S14): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / OFFICIAL-MHRA (S15): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / OFFICIAL-DMLABEL (S16): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-CHENAD2021 (S17): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-CYCLISTS2026 (S19): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-BERG2025 (S20): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. Within the original review scope, the number of verified directly eligible results is 0. This does not mean worldwide absence of human research or an effect of 0. Family labels are not summed as independent trial counts or participant numbers.", "unique_trial_count": null, "unique_participant_count": null, "reason": "These are the report linkages in the stored manuscript. TF-MA2019 (S01, S02, S03, S21): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-KWOK2017 (S04, S18): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-KWOK2020 (S05): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-ZHOU2023 (S06): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-EUSSEN2006 (S07): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-DANGOUR2015 (S08): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-JATOI2020 (S09): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-VITACOG (S10): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-LAUER2022 (S11): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-MARKUN2021 (S12): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-ELGAR2022 (S13): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / OFFICIAL-ODS (S14): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / OFFICIAL-MHRA (S15): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / OFFICIAL-DMLABEL (S16): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-CHENAD2021 (S17): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / TF-CYCLISTS2026 (S19): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. / REVIEW-BERG2025 (S20): The current evidence family ID and the relationships among bibliographic records, registration and duplicate abstracts were linked. No inference about collections or independent trial counts was made. Within the original review scope, the number of verified directly eligible results is 0. This does not mean worldwide absence of human research or an effect of 0. Family labels are not summed as independent trial counts or participant numbers." }, "history": [ { "date": "2026-11-05", "kind": "Separation of public-facing display and data", "view_version": "1.0", "change": "The public-facing display and data were prepared from the existing 43 items. No new clinical search, change of verification status or scoring was performed." } ], "language": "en", "translation_date": "2026-11-05" }