# Oral vitamin B12 as the sole added active ingredient × Improvement in global cognition in adults with clinically defined MCI Verdict 3112 · Evidence Check Stored-material review date: 2026-10-05 Original evidence date: 2026-09-16 Review-criteria version: NGM-v3112-ORAL-B12-MCI-GLOBAL-1.0 Public page/material preparation date: 2026-11-05 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Adults with clinically defined MCI; distinguish correction of deficiency from supplementation in replete or unverified status; detailed Ma2019 criteria and baseline status unverified - Ingredient, formulation and route: 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 - Measured outcome: 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 - Questions outside this scope: 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. ## Checklist items ### N01 · Which MCI population, B12 comparison and global cognition outcome does this table address? Verification status: Met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The original claim and the boundaries of the distinct question were linked. This does not mean an efficacy estimate was verified. - Reason for missing information: Actual eligible monotherapy-arm results and the prespecified main timepoint remain separately unverified. - Required materials and conditions: Original claim and fixed question; specifications of population, ingredient, route, outcome, comparator and timepoint - Materials to obtain first: Original claim and fixed question; specifications of population, ingredient, route, outcome, comparator and timepoint - Further 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. - Conditions for verification: Link the oral comparison in MCI with B12 as the sole added active ingredient to the global cognition score, and exclude other questions. - Why this condition is needed: Required to avoid combining the page's cognition, dementia and deficiency questions into a single efficacy claim. - Application exceptions: Verification of the claim boundaries does not establish an eligible trial or an improvement effect. - Remaining uncertainty: Actual eligible monotherapy-arm results and the prespecified main timepoint remain separately unverified. - Referenced methods: 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 - Related sources: ### N02 · Does the MCI label in Ma2019 satisfy the actual clinical diagnostic criteria? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The MCI label is preserved, but details of clinical eligibility are unverified. - Reason for missing information: The label cannot substitute for evidence of diagnostic details. - Required materials and conditions: Original material on the diagnostic system, diagnostician, objective criteria, ADL, dementia exclusion, subtypes and age/sex - Materials to obtain first: Original material on the diagnostic system, diagnostician, objective criteria, ADL, dementia exclusion, subtypes and age/sex - Further research: Document diagnostic criteria and procedures for assessing daily functioning and excluding dementia, prespecify MCI subtypes and present results by population. - Conditions for verification: Assess population directness by distinguishing the reported MCI label from unverified diagnostic details. - Why this condition is needed: Required to avoid treating the diagnostic label alone as verification of confirmed MCI, preserved daily functioning or exclusion of dementia. - Application exceptions: Do not turn unverified detailed criteria into a definite conclusion that the participants did not have clinical MCI. - Remaining uncertainty: The label cannot substitute for evidence of diagnostic details. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed - Related sources: S01, S03 ### N03 · Can correction of deficiency be distinguished from supplementation in replete or unverified status? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: In Ma2019, baseline serum B12, functional markers, folate, hematologic status, deficient/borderline/replete thresholds and results by stratum are unverified. - Why unverified: The clinical MCI label alone cannot establish effects by B12 status. - Reason for missing information: Do not infer efficacy regardless of status or the absence of anemia. - Required materials and conditions: Baseline B12/holotranscobalamin/MMA, homocysteine, folate, Hb/MCV, deficiency thresholds and results by stratum - Materials to obtain first: Baseline B12/holotranscobalamin/MMA, homocysteine, folate, Hb/MCV, deficiency thresholds and results by stratum - Further research: Prespecify baseline B12 status categories, and separately analyze interactions/stratified comparisons for correction of deficiency and add-on treatment in replete status. - Conditions for verification: Link only the verified scope of baseline status, thresholds and direct results in each stratum. - Why this condition is needed: Required to avoid extending correction of deficiency-related cognitive impairment to MCI efficacy regardless of status. - Application exceptions: Do not fill in unreported baseline tests with assumptions of replete status or normal hematologic status. - Remaining uncertainty: Do not infer efficacy regardless of status or the absence of anemia. - Referenced methods: 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 - Related sources: S01, S03 ### N04 · Were the actual chemical form, formulation and product in the B12 monotherapy arm verified? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: The chemical form, salt, manufacturer, tablet/capsule, release formulation, product, batch and purity in the Ma2019 monotherapy arm are all unverified. - Why unverified: cyanocobalamin, methylcobalamin/mecobalamin, hydroxocobalamin and adenosylcobalamin were not verified as the same preparation. - Reason for missing information: Do not fill in the chemical form from another trial or an official warning. - Required materials and conditions: Original records of chemical form, salt, manufacturer, dosage/release formulation, product, batch and purity - Materials to obtain first: Original records of chemical form, salt, manufacturer, dosage/release formulation, product, batch and purity - Further research: Use an identifiable single-ingredient B12 formulation and report product, batch, purity and exposure to the chemical form by arm. - Conditions for verification: Link the actual product attributes of the monotherapy arm to original material, retaining missing values. - Why this condition is needed: Required to avoid combining different cobalamin chemical forms and products as the same intervention. - Application exceptions: Distinguish the question's definition of a single active ingredient from verification of the actual trial product. - Remaining uncertainty: Do not fill in the chemical form from another trial or an official warning. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed - Related sources: S01, S03 ### N05 · Should this question require distinctions between plant parts? Verification status: Not applicable Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: The retained structure records plant_part as not_applicable and explains that a chemical nutrient is not a plant-part intervention. - Why unverified: The plant-part criterion does not apply to this narrow B12 question. - Reason for missing information: Product, manufacturer and purity remain unverified in N04. - Required materials and conditions: Distinction between a chemical nutrient intervention and a plant-derived intervention - Materials to obtain first: Distinction between a chemical nutrient intervention and a plant-derived intervention - Further research: Obtain actual B12 product and chemical-form material to assess identity criteria without adding plant-part research. - Conditions for verification: Link the retained reason that plant_part is not applicable to the chemical ingredient question. - Why this condition is needed: Considered to avoid mechanically imposing a plant-part criterion on a chemical nutrient question. - Application exceptions: Nonapplicability of plant part does not waive verification of the manufacturer, product or purity. - Remaining uncertainty: Product, manufacturer and purity remain unverified in N04. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed - Related sources: ### N06 · Was oral administration in the B12 monotherapy arm verified from original material? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Some route leads exist, but there is no independent verification from original material for the monotherapy arm. - Reason for missing information: Do not turn the oral scope of the question into a record verifying the actual route in every arm. - Required materials and conditions: Route, formulation and schedule by arm, and the original methods for the monotherapy arm - Materials to obtain first: Route, formulation and schedule by arm, and the original methods for the monotherapy arm - Further research: Specify oral administration and its schedule in the monotherapy arm, and report injection, sublingual and mixed routes as separate comparisons. - Conditions for verification: Distinguish the page's oral-route question from the actual oral combination arm and the unverified monotherapy arm. - Why this condition is needed: Required to avoid treating the word oral for the combination arm as verification of the monotherapy arm's route. - Application exceptions: Distinguish the review's oral-route lead from verification of the original monotherapy arm. - Remaining uncertainty: Do not turn the oral scope of the question into a record verifying the actual route in every arm. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed - Related sources: S01, S03 ### N07 · Can 25 µg/day be used as the established monotherapy-arm dose? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The structure explicitly states secondary_report_only_not_primary_verified and not_used_as_actual_trial_dose. - Reason for missing information: Do not use these values to determine a personal or optimal dose. - Required materials and conditions: Original amount per administration (1 time), daily amount and frequency in the monotherapy arm, and the original source cited by the review - Materials to obtain first: Original amount per administration (1 time), daily amount and frequency in the monotherapy arm, and the original source cited by the review - Further 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. - Conditions for verification: Distinguish the reports of B12 25 µg and folic acid 800 µg as secondary (2nd) information, and preserve the unverified original monotherapy-arm dose. - Why this condition is needed: Required to avoid turning the review's dose lead into a verified value for the original monotherapy arm or a personal dose. - Application exceptions: Retain the lead without promoting it to an established daily amount, amount per administration (1 time) or frequency. - Remaining uncertainty: Do not use these values to determine a personal or optimal dose. - Referenced methods: 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 - Related sources: S11, S13 ### N08 · Does the combination-arm versus folic-acid-arm comparison differ only in B12? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The conditional candidate for added B12 is preserved but is not currently counted as a directly eligible result. - Reason for missing information: Do not delete the favorable statement or assume matching backgrounds. - Required materials and conditions: Folic acid dose, same background treatment, added ingredients and actual exposure in both C02 arms - Materials to obtain first: Folic acid dose, same background treatment, added ingredients and actual exposure in both C02 arms - Further research: Randomize only added B12 on the same folic acid and usual-care background, and prespecify analysis of the same global cognition effect. - Conditions for verification: Interpret the contrast as B12 being the sole added ingredient only when the matched background is verified. - Why this condition is needed: Required to avoid attributing multiple active ingredients or different backgrounds to an added B12 effect. - Application exceptions: 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. - Remaining uncertainty: Do not delete the favorable statement or assume matching backgrounds. - Referenced methods: 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 - Related sources: S01, S03 ### N09 · Was an untreated control distinguished from matched placebo and the same care? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: An untreated control was reported in Ma2019. Matched placebo composition and the common background across arms are unverified. - Why unverified: Part of the actual control type was verified, but the background and placebo conditions matching the question were not. - Reason for missing information: Do not substitute an untreated control for a fully matched placebo or usual-care comparison. - Required materials and conditions: Actual treatment, placebo composition, background and rescue treatment in the control arm - Materials to obtain first: Actual treatment, placebo composition, background and rescue treatment in the control arm - Further research: Document the actual treatment and the same background in the comparator of interest, and examine differences in contact and assessment in the analysis. - Conditions for verification: Distinguish the reported untreated control from the page's eligible comparator criteria. - Why this condition is needed: Required to avoid presenting an untreated arm as a blinded matched placebo arm. - Application exceptions: Do not erase the existence of the actual untreated arm because placebo composition is unverified. - Remaining uncertainty: Do not substitute an untreated control for a fully matched placebo or usual-care comparison. - Referenced methods: 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 - Related sources: S01, S03 ### N10 · Were actual total B12 exposure and conditions affecting absorption or concomitant use distinguished? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: Adherence, diet/fortified foods, concurrent supplementation, total B12 exposure, malabsorption and metformin/PPI use are unverified in the core candidate. - Why unverified: No direct records are available to examine differences in background exposure or absorption between arms. - Reason for missing information: Do not transfer official information about these influences into facts about individual concomitant use in Ma2019. - Required materials and conditions: Records by arm of adherence/measurement method, diet/fortification/additional supplements, malabsorption and metformin/PPI - Materials to obtain first: Records by arm of adherence/measurement method, diet/fortification/additional supplements, malabsorption and metformin/PPI - Further research: Track exposure, adherence, absorption and concomitant medications, and prespecify separate analyses of the assignment effect and adherence-related effects. - Conditions for verification: Distinguish the nominal intervention from actual exposure and background differences according to their verification level. - Why this condition is needed: Required to avoid confusing diet, other supplements and conditions affecting absorption with the randomized dose. - Application exceptions: Do not fill in unreported information with normal absorption, high adherence or absence of concomitant use. - Remaining uncertainty: Do not transfer official information about these influences into facts about individual concomitant use in Ma2019. - Referenced methods: 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 - Related sources: S01, S03, S14 ### N11 · Was the reported 6-month timepoint verified as the prespecified main timepoint? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: The administration period and the page review timepoint are recorded as 6 months. The prespecified main timepoint and actual main analysis timepoint are unverified. - Why unverified: The reported duration is verified, but the prespecified hierarchy of timepoints is not. - Reason for missing information: The duration of 6 months alone does not establish a sustained effect or an optimal duration. - Required materials and conditions: Administration period, assessment timepoints, registered main timepoint and records of endpoint changes - Materials to obtain first: Administration period, assessment timepoints, registered main timepoint and records of endpoint changes - Further research: Prespecify the main assessment timepoint for global cognition, and report later timepoints and follow-up after discontinuation as separate analyses. - Conditions for verification: Distinguish the 6-month report from the verification level of preregistration and analysis timepoints. - Why this condition is needed: Required to avoid confusing the reported duration with the prespecified main analysis timepoint. - Application exceptions: Preserve the page's 6-month review timepoint without labeling it as the registered main timepoint. - Remaining uncertainty: The duration of 6 months alone does not establish a sustained effect or an optimal duration. - Referenced methods: 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 - Related sources: S01, S03 ### N12 · Were the actual testing conditions for WAIS-RC FSIQ verified? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The scale name and direction are available, but actual administration conditions are not sufficiently verified. - Reason for missing information: Do not substitute MoCA, MMSE or a single memory domain for this outcome. - Required materials and conditions: Scale version/manual, score range, language, education adjustment, administration/practice effects and direction - Materials to obtain first: Scale version/manual, score range, language, education adjustment, administration/practice effects and direction - Further research: Administer the same validated global scale using standardized procedures, with prespecified handling of education, language and repeated-testing effects. - Conditions for verification: Distinguish the reported WAIS-RC FSIQ from unverified testing conditions. - Why this condition is needed: Required to avoid substituting another cognitive scale or a domain result for the same global score outcome. - Application exceptions: Preserve the reported scale and direction without inferring its version or score range. - Remaining uncertainty: Do not substitute MoCA, MMSE or a single memory domain for this outcome. - Referenced methods: 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 - Related sources: S01, S03 ### N13 · Was the prespecified primary endpoint on the global scale checked against the ChiCTR record? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The retained record is inaccessible_registry; current web access/reading has not been attempted. - Reason for missing information: Do not construct a primary-endpoint hierarchy from search snippets or the registration number alone. - Required materials and conditions: Original registration date, original/changed endpoints, protocol, SAP and reasons for changes - Materials to obtain first: Original registration date, original/changed endpoints, protocol, SAP and reasons for changes - Further research: Link the registration, protocol and SAP in advance and make the original/changed endpoints available for comparison with reported results. - Conditions for verification: Label primary status only according to the hierarchy actually obtained, and retain the unavailable information as such. - Why this condition is needed: Required to avoid treating the existence of a registration number as successful comparison against the protocol/SAP. - Application exceptions: Distinguish historical access failure from access not attempted in this exercise, without establishing nonregistration or selective reporting. - Remaining uncertainty: Do not construct a primary-endpoint hierarchy from search snippets or the registration number alone. - Referenced methods: 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 - Related sources: S03 ### N14 · Were the actual sequence and allocation concealment for the 4-arm randomization verified? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: Ma2019 was reported as a 4-arm randomized single-blind trial. The actual sequence, allocation concealment and baseline balance are unverified. - Why unverified: The design label is verified, but direct methods material on the allocation process is unavailable. - Reason for missing information: Do not assign an official RoB score or a new bias grade. - Required materials and conditions: Allocation sequence, concealment, baseline balance and recruitment/selection procedures by arm - Materials to obtain first: Allocation sequence, concealment, baseline balance and recruitment/selection procedures by arm - Further research: Disclose the allocation sequence, concealment and baseline characteristics by arm, and prespecify analysis of the assignment effect. - Conditions for verification: Link the report of 4-arm randomization to the verification level of the actual allocation methods. - Why this condition is needed: Required to avoid claiming that the randomized-trial label alone resolves allocation bias concerns. - Application exceptions: Retain the report of randomization and do not turn unverified information into a high-risk judgment. - Remaining uncertainty: Do not assign an official RoB score or a new bias grade. - Referenced methods: 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 - Related sources: S01, S03 ### N15 · Who was blinded in the single-blind design? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: The single-blind label is preserved, but who was blinded is unverified. - Why unverified: The blinding label was not used as a substitute for verification of who was actually blinded. - Reason for missing information: Do not turn unverified information into a definite conclusion of success or failure. - Required materials and conditions: Participant/assessor/analyst blinding, procedures and contact by arm - Materials to obtain first: Participant/assessor/analyst blinding, procedures and contact by arm - Further research: Specify blinding of cognitive assessors and analysts and contact by arm, and maintain matching assessment procedures. - Conditions for verification: Distinguish the single-blind label from unverified information about each role and assessment conditions. - Why this condition is needed: Required to examine cognitive testing and differences in expectations/contact between arms. - Application exceptions: Do not turn unverified information about who was blinded into a definite finding of blinding failure. - Remaining uncertainty: Do not turn unverified information into a definite conclusion of success or failure. - Referenced methods: M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application - Related sources: S01, S03 ### N16 · Were 240 participants, 4 arms and the inferred 60 participants distinguished from analysis denominators? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The sources of the total number and historical calculation were distinguished, but actual flow by arm remains unverified. - Reason for missing information: Do not use 60 as the analysis n, completion n or adverse-event denominator. - Required materials and conditions: Flow diagram of actual allocation, completion and analysis overall/by arm, distinguished from the historical calculation - Materials to obtain first: Flow diagram of actual allocation, completion and analysis overall/by arm, distinguished from the historical calculation - Further 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. - Conditions for verification: 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. - Why this condition is needed: Required to avoid turning the total randomized number and a historical arithmetic inference into original arm-specific analysis counts. - Application exceptions: Preserve the existing 60 participants only as a historical calculated value; do not recalculate it in this exercise. - Remaining uncertainty: Do not use 60 as the analysis n, completion n or adverse-event denominator. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed - Related sources: S01, S03 ### N17 · Were the monotherapy-arm analysis count, ITT/PP and handling of dropouts verified? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Direct material is unavailable to examine the analysis denominator and handling of missing data for the between-group outcome of interest. - Reason for missing information: Do not turn the total of 240 participants into the analysis n for the target effect. - Required materials and conditions: Completion/analysis/dropouts by arm, ITT/PP, missing data/imputation and analysis population - Materials to obtain first: Completion/analysis/dropouts by arm, ITT/PP, missing data/imputation and analysis population - Further research: Report actual denominators and reasons for missing data by arm, and prespecify the main analysis of the assignment effect, imputation and sensitivity analyses. - Conditions for verification: Link the verification scope of the monotherapy-arm denominators and missing-data handling to the results. - Why this condition is needed: Required to avoid treating the reported total alone as verification of complete follow-up or an ITT analysis. - Application exceptions: Do not fill in missing analysis denominators or dropout counts with 0 or 60. - Remaining uncertainty: Do not turn the total of 240 participants into the analysis n for the target effect. - Referenced methods: 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 - Related sources: S01, S03 ### N18 · Were the global cognition difference, CI and P for B12 alone versus control verified? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: The structured global cognition effect, CI and P for B12 versus control are left blank. A directly eligible monotherapy estimate was not verified. - Why unverified: The current input lacks the between-group numbers of interest, so the magnitude and precision of improvement cannot be established. - Reason for missing information: Do not transfer d = 0.169, P = 0.024 to this contrast. - Required materials and conditions: Original monotherapy-arm between-group estimate for the main global cognition outcome, unit, timepoint, denominator, CI/P and original table - Materials to obtain first: Original monotherapy-arm between-group estimate for the main global cognition outcome, unit, timepoint, denominator, CI/P and original table - Further research: Publish the prespecified between-group global cognition difference, CI and denominator for the B12 monotherapy contrast on the same background. - Conditions for verification: Display an effect for the monotherapy contrast of interest only when its actual estimate is verified. - Why this condition is needed: Required to avoid transferring combination-arm numbers or review wording to the original monotherapy-arm effect. - Application exceptions: The currently unverified direct values do not constitute a judgment of an effect of 0 or no effect. - Remaining uncertainty: Do not transfer d = 0.169, P = 0.024 to this contrast. - Referenced methods: 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 - Related sources: S01, S03 ### N19 · Which comparison do d = 0.169 and P = 0.024 refer to? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The reported numbers and comparison are preserved, but they cannot be interpreted as the effect of B12 alone or as establishing clinical importance. - Reason for missing information: Do not reconstruct a monotherapy effect, CI or MCID from a P value. - Required materials and conditions: Original abstract for the combination arm versus no treatment, effect definition/method of calculating d, timepoint and denominator - Materials to obtain first: Original abstract for the combination arm versus no treatment, effect definition/method of calculating d, timepoint and denominator - Further research: Prespecify combination and monotherapy contrasts separately, and provide each contrast's between-group estimate, denominator, CI and effect definition separately. - Conditions for verification: Attribute the current positive numbers only to the actual combination contrast. - Why this condition is needed: Required to avoid using the positive combination-arm result as the effect of B12 alone. - Application exceptions: Retain results that are not unfavorable as well, attributing them to the actual combination comparison. - Remaining uncertainty: Do not reconstruct a monotherapy effect, CI or MCID from a P value. - Referenced methods: 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 - Related sources: S01 ### N20 · How is the favorable post hoc statement for combination versus folic acid preserved? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The add-on effect candidate is preserved, but essential aspects of direct-result verification remain unresolved. - Reason for missing information: Do not transfer the d/P for C01 to the numbers for C02. - Required materials and conditions: Original C02 results, same background, estimate/CI/P and whether the contrast was prespecified - Materials to obtain first: Original C02 results, same background, estimate/CI/P and whether the contrast was prespecified - Further 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. - Conditions for verification: Record the conditional add-on candidate together with the currently unverified eligible numbers. - Why this condition is needed: Required to consider the possibility of the same folic acid background without turning a conditional candidate into a confirmed comparison. - Application exceptions: Do not delete the favorable statement because it comes from a post hoc comparison, but do not promote it to a prespecified primary endpoint. - Remaining uncertainty: Do not transfer the d/P for C01 to the numbers for C02. - Referenced methods: 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 - Related sources: S01, S03 ### N21 · Were the repeated-measures model and the printed Turkey distinguished from the actual analysis? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: There are leads about the model and post hoc label, but the confirmed analysis for a particular main contrast cannot be reconstructed. - Reason for missing information: This does not justify inferred corrections or selection of favorable analyses after the fact. - Required materials and conditions: Original analysis section, model/covariates for each contrast, post hoc method, multiple comparisons and main/sensitivity distinction - Materials to obtain first: Original analysis section, model/covariates for each contrast, post hoc method, multiple comparisons and main/sensitivity distinction - Further research: Prespecify the model, covariates, main/sensitivity analyses and handling of multiple comparisons for each contrast, and report whether the original printing was corrected. - Conditions for verification: Distinguish the reported ANOVA/mixed models from unverified contrast-specific plans. - Why this condition is needed: Required to avoid inferring a confirmed analysis for a particular contrast from a model category or post hoc label. - Application exceptions: Do not silently correct the original printed Turkey to Tukey. - Remaining uncertainty: This does not justify inferred corrections or selection of favorable analyses after the fact. - Referenced methods: M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application - Related sources: S01, S03 ### N22 · Were SD, SE, CI and an important difference in MCI verified? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Without a direct effect, interval or importance threshold, adequacy and clinical meaning cannot be determined. - Reason for missing information: Do not generate new SD/SE/CI, minimum participant numbers, trial counts or durations. - Required materials and conditions: Original baseline/change/endpoint means, type of dispersion, CI and the applicable MCI/scale/between-group MCID - Materials to obtain first: Original baseline/change/endpoint means, type of dispersion, CI and the applicable MCI/scale/between-group MCID - Further 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. - Conditions for verification: Link the verification level of dispersion, intervals and an important difference to the reasons interpretation is not possible. - Why this condition is needed: Required to avoid deciding precision and clinical meaning from significance, trial count or total n alone. - Application exceptions: Do not import another scale's MCID or a generic d = 0.2. - Remaining uncertainty: Do not generate new SD/SE/CI, minimum participant numbers, trial counts or durations. - Referenced methods: 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 - Related sources: S01, S03 ### N23 · Was the review's description of a nonsignificant B12 monotherapy result counted as an original result? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The unfavorable lead is retained, but verification of the original nonsignificant monotherapy result remains outstanding. - Reason for missing information: Do not count the review as an independent trial showing no B12 effect or as an original P value. - Required materials and conditions: The S13 citation concerning nonsignificant monotherapy and the original monotherapy table/CI and denominators - Materials to obtain first: The S13 citation concerning nonsignificant monotherapy and the original monotherapy table/CI and denominators - Further research: Disclose the complete original monotherapy comparison results, CIs and reporting selections to compare positive and nonsignificant results using the same criteria. - Conditions for verification: Distinguish a review lead from an interpretation of no difference that has not been verified in original material. - Why this condition is needed: Required to preserve a contrary lead without promoting the review to verification of original monotherapy numbers. - Application exceptions: Do not turn nonsignificance into an effect of 0, equivalence or established absence of effect. - Remaining uncertainty: Do not count the review as an independent trial showing no B12 effect or as an original P value. - Referenced methods: 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 - Related sources: S13 ### N24 · Can Kwok2017, with 271 participants, be used as an independent result for clinical MCI? Verification status: Not met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: 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. - Reason for missing information: There is no separate MCI estimate, and the proportion with CDR 0.5 alone does not establish the diagnosis. - Required materials and conditions: Definition of the clinical MCI stratum, its separate main global cognition result and original denominator/interval - Materials to obtain first: Definition of the clinical MCI stratum, its separate main global cognition result and original denominator/interval - Further research: Prespecify the clinical MCI stratum and report its monotherapy comparison and main global score/CI separately. - Conditions for verification: Use only the verified scope of direct comparisons in the whole cohort and a separately identified MCI stratum. - Why this condition is needed: Required to avoid substituting a mixed nondemented diabetic population and CDR 0.5 for a confirmed MCI stratum. - Application exceptions: Do not exclude a study with an actual B12 monotherapy arm on ingredient grounds. - Remaining uncertainty: There is no separate MCI estimate, and the proportion with CDR 0.5 alone does not establish the diagnosis. - Referenced methods: 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 - Related sources: S04, S18 ### N25 · Does Kwok2020, with 279 participants and CDR-SOB at 24 months, provide a result for B12 alone? Verification status: Not met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The actual contrast involves multiple active ingredients and cannot be used as this page's B12 monotherapy contrast for global cognition. - Reason for missing information: Do not transfer numbers for a different endpoint or timepoint to WAIS-RC at 6 months. - Required materials and conditions: Composition of the methylcobalamin/folic acid arm, original CDR-SOB results at 24 months and a contrast differing only in B12 - Materials to obtain first: Composition of the methylcobalamin/folic acid arm, original CDR-SOB results at 24 months and a contrast differing only in B12 - Further research: Design a contrast differing only in B12 on the same background, and prespecify the effect of interest on the global scale. - Conditions for verification: Even within MCI, distinguish multiple active ingredients and a different primary endpoint. - Why this condition is needed: Required to avoid attributing a multiple-ingredient effect to B12 alone merely because the MCI population matches. - Application exceptions: Preserve the combination treatment's original result and duration without decomposing them into monotherapy-arm numbers. - Remaining uncertainty: Do not transfer numbers for a different endpoint or timepoint to WAIS-RC at 6 months. - Referenced methods: 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 - Related sources: S05 ### N26 · In Eussen2006, what is the scope of the 195 participants and the memory result favoring placebo? Verification status: Not met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The criterion of separating a direct main global cognition estimate in MCI was not met. The unfavorable domain result was not omitted. - Reason for missing information: Do not repurpose the memory domain as the global WAIS-RC effect or as no effect in MCI. - Required materials and conditions: Separate clinical MCI stratum/main global result, original memory-domain table and DOI identity - Materials to obtain first: Separate clinical MCI stratum/main global result, original memory-domain table and DOI identity - Further research: Separate the monotherapy contrast in clinical MCI, and report global cognition and the memory domain in separate plans/results. - Conditions for verification: Preserve the deficient population with mixed cognitive status and the domain result favoring placebo within their original scope. - Why this condition is needed: Required to distinguish biochemical deficiency, mixed cognitive status and domain results. - Application exceptions: An actual B12 monotherapy arm exists; do not exclude the study because it also has a combination arm. - Remaining uncertainty: Do not repurpose the memory domain as the global WAIS-RC effect or as no effect in MCI. - Referenced methods: 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 - Related sources: S07 ### N27 · Were the routes and printed dose/dropout inconsistencies in Zhou2023 distinguished? Verification status: Conflicting information Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The original review's inconsistencies concerning unusual units/dropout rates were linked unchanged. They were not reverified against newly read clinical original material. - Reason for missing information: The direct criteria also do not match; do not correct the original values or transfer incidence from another formulation. - Required materials and conditions: Dose unit, route/chemical form, flow diagram, dropout-rate table and corrections in the original Methods - Materials to obtain first: Dose unit, route/chemical form, flow diagram, dropout-rate table and corrections in the original Methods - Further research: Compare units and dropout flow in the original tables/Methods, and separately design an oral single-chemical-form contrast in clinical MCI. - Conditions for verification: Link only the boundaries of the mixed regimen and the currently retained record of inconsistencies. - Why this condition is needed: Required to avoid turning injection followed by two oral chemical forms in broad cognitive impairment into oral monotherapy in MCI. - Application exceptions: Do not arbitrarily correct the printed 500 mg unit or dropout-rate inconsistencies recorded by the original review to another unit or value. - Remaining uncertainty: The direct criteria also do not match; do not correct the original values or transfer incidence from another formulation. - Referenced methods: 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 - Related sources: S06 ### N28 · In Jatoi2020, are the before-and-after MMSE responses in 202 participants a between-group effect? Verification status: Conflicting information Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: 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. - Reason for missing information: Do not turn before-and-after improvement into a direct between-group effect or universal efficacy regardless of deficiency status. - Required materials and conditions: Control/allocation, original MMSE response table/participant counts and definition of the deficient population - Materials to obtain first: Control/allocation, original MMSE response table/participant counts and definition of the deficient population - Further research: Use an appropriate control on the same background, and report the clinical MCI population and global-scale effect with denominators/intervals. - Conditions for verification: Specify the limitations of uncontrolled before-and-after results and inconsistent participant counts. - Why this condition is needed: Required to distinguish before-and-after improvement after correction of deficiency from efficacy versus placebo. - Application exceptions: Preserve inconsistent counts in the original abstract without reconstructing detailed subgroup counts absent from the current material. - Remaining uncertainty: Do not turn before-and-after improvement into a direct between-group effect or universal efficacy regardless of deficiency status. - Referenced methods: 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 - Related sources: S09 ### N29 · Were the 271 participants and subsequent imaging reports from VITACOG counted as independent monotherapy replications? Verification status: Not met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Multiple active ingredients, different endpoints and reports from the same family do not satisfy the direct criteria for the narrow monotherapy effect. - Reason for missing information: Do not repurpose MRI brain atrophy as improvement in global cognition scores or prevention of dementia. - Required materials and conditions: VITACOG registration/report family and linkage of the three active ingredients to original/subsequent endpoints - Materials to obtain first: VITACOG registration/report family and linkage of the three active ingredients to original/subsequent endpoints - Further research: Link overlapping participants by trial family, and separately design/analyze the B12 monotherapy contrast and main global cognition outcome. - Conditions for verification: Distinguish the B12/folic acid/B6 combination contrast from imaging within the same trial family. - Why this condition is needed: Required to avoid double-counting combined B vitamins and subsequent reports from the same trial as B12 monotherapy replications. - Application exceptions: Retain the original imaging and cognition reports without creating separate independent trial counts. - Remaining uncertainty: Do not repurpose MRI brain atrophy as improvement in global cognition scores or prevention of dementia. - Referenced methods: 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 - Related sources: S10 ### N30 · Was Chen's combination trial in Alzheimer's disease used as a monotherapy effect in MCI? Verification status: Not met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The direct criteria for both population and added active ingredients differ from this question. - Reason for missing information: Retain the original results, but do not transfer them as monotherapy efficacy or participant numbers in MCI. - Required materials and conditions: Alzheimer's disease population, folic acid/B12 composition, original n/endpoints and a separate MCI contrast - Materials to obtain first: Alzheimer's disease population, folic acid/B12 composition, original n/endpoints and a separate MCI contrast - Further research: Separately design a comparison in clinical MCI differing only in B12, and distinguish it from AD results. - Conditions for verification: Preserve the AD/combination boundaries and unverified original numbers within their original scope. - Why this condition is needed: Required to avoid extending material differing in both diagnosis and ingredients to a direct effect in MCI. - Application exceptions: If the original n is absent from the current material, do not fill it in with participant numbers from another study. - Remaining uncertainty: Retain the original results, but do not transfer them as monotherapy efficacy or participant numbers in MCI. - Referenced methods: 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 - Related sources: S17 ### N31 · Were unverified original numbers from Dangour2015 used as current direct evidence? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Bibliographic existence is verified, but material establishing the population, endpoint or effect for this narrow question is unavailable. - Reason for missing information: Current web access has not been attempted, and no original numbers are newly filled in. - Required materials and conditions: Original population, dose, denominator/global scale and the main result in the clinical MCI stratum - Materials to obtain first: Original population, dose, denominator/global scale and the main result in the clinical MCI stratum - Further research: Assess eligibility after obtaining original population/endpoint/separate-stratum material, and design a clinical MCI monotherapy contrast if needed. - Conditions for verification: Distinguish bibliographic discovery from unverified direct material. - Why this condition is needed: Required to distinguish a discovered RCT bibliographic record from an unobtained full text and unavailable population details. - Application exceptions: Do not label historical full-text access failure as a failure in this exercise, or turn failure to obtain material into absence of research. - Remaining uncertainty: Current web access has not been attempted, and no original numbers are newly filled in. - Referenced methods: 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 - Related sources: S08 ### N32 · Was the 2026 cyclist study extrapolated to clinical MCI? Verification status: Not met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The verified population differs from the narrow clinical MCI criterion. - Reason for missing information: Do not derive directness or an original effect from recency or a crossover title. - Required materials and conditions: Original population/results, whether clinical MCI was present and bibliographic identity - Materials to obtain first: Original population/results, whether clinical MCI was present and bibliographic identity - Further research: Separately review/design the monotherapy comparison in clinical MCI, without pooling it with performance results in athletes. - Conditions for verification: Distinguish the amateur-cyclist title from the clinical MCI question. - Why this condition is needed: Required to avoid extending an effect in another population to MCI merely because it is a recent cognitive-performance study. - Application exceptions: Retain the bibliographic lead without generating an original n or effect size in this exercise. - Remaining uncertainty: Do not derive directness or an original effect from recency or a crossover title. - Referenced methods: 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 - Related sources: S19 ### N33 · Were review averages or the 2025 lead counted as direct monotherapy estimates? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Material to verify an original direct monotherapy result or a separate estimate from an eligible review is currently unavailable. - Reason for missing information: Do not add review counts to included-trial counts or use a broad average as an efficacy value. - Required materials and conditions: Included-study tables, original identities and separate estimates for MCI/monotherapy/global outcomes in the reviews - Materials to obtain first: Included-study tables, original identities and separate estimates for MCI/monotherapy/global outcomes in the reviews - Further research: Link included studies and original contrasts by family, and separately organize only material meeting the same direct criteria. - Conditions for verification: Distinguish the actual mapping roles of S11/S12/S13/S20 from the unverified status of original values. - Why this condition is needed: Required to avoid promoting a broad B-vitamin/cognition review to a narrow MCI monotherapy effect. - Application exceptions: Preserve the reviews' negative/positive leads and access limitations without describing the search as complete. - Remaining uncertainty: Do not add review counts to included-trial counts or use a broad average as an efficacy value. - Referenced methods: 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 - Related sources: S11, S12, S13, S20 ### N34 · Were the 21 reports counted as unique independent monotherapy trials? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Verified linkages within the same families were preserved, but no new count of eligible unique direct trials was established. - Reason for missing information: Do not count VITACOG follow-up reports/reviews as new independent B12 replications. - Required materials and conditions: Relationships among Ma/registration/author abstracts, Kwok registration and the VITACOG follow-up family - Materials to obtain first: Relationships among Ma/registration/author abstracts, Kwok registration and the VITACOG follow-up family - Further research: Link each report to a unique trial and its original contrast/timepoint to separate duplication before assessing replication. - Conditions for verification: Link report-specific roles and family IDs, and leave the unconfirmed count of unique direct trials blank. - Why this condition is needed: Required to avoid double-counting abstracts, bibliographic records, registration, reviews or subsequent reports of the same Ma2019 study as independent replications. - Application exceptions: Retain provisional linkages/unverified status for families lacking sufficient identity material. - Remaining uncertainty: Do not count VITACOG follow-up reports/reviews as new independent B12 replications. - Referenced methods: 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 - Related sources: S01, S02, S03, S04, S10, S18, S21 ### N35 · Were 0 directly eligible results distinguished from the existence of human research? Verification status: Met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The original verdict, limited scope and explanation of the historical calculation were linked unchanged. This does not mean the direct efficacy criteria were met. - Reason for missing information: The legacy calculator's inability to validate the original factual profile is also preserved; no efficacy value of 0 is created. - Required materials and conditions: Original evidence date, existence of human research/direct eligibility status, original grade/score and explanation of the historical calculation - Materials to obtain first: Original evidence date, existence of human research/direct eligibility status, original grade/score and explanation of the historical calculation - Further research: If the original search/eligibility record is updated, disclose the direct criteria for population, ingredient, outcome and duration, together with exclusion reasons. - Conditions for verification: Distinguish the scope as of 2026-09-16 from the reading for conversion on 2026-10-05 and from the original verdict. - Why this condition is needed: Required to avoid turning unverified information in the current scope into worldwide absence of research or an effect of 0. - Application exceptions: Preserve the original no_human_study=false and stage-gate projection without rerunning the legacy calculator. - Remaining uncertainty: The legacy calculator's inability to validate the original factual profile is also preserved; no efficacy value of 0 is created. - Referenced methods: 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 - Related sources: ### N36 · Does the global score also answer questions about conversion to dementia, daily functioning and brain atrophy? Verification status: Not applicable Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: A trial of dementia events is not imposed as a prerequisite for this narrow global-score assessment. That extended claim is unverified. - Reason for missing information: No judgment of absence of events or absence of an effect on events is made either. - Required materials and conditions: Separate direct results and interpretive scope for events/daily functioning and the global scale - Materials to obtain first: Separate direct results and interpretive scope for events/daily functioning and the global scale - Further research: When separately planning claims about conversion to dementia, daily functioning or quality of life, design direct measurements of the corresponding events/functions. - Conditions for verification: Do not substitute global FSIQ, domain tests, brain volume, blood B12/homocysteine or dementia for one another. - Why this condition is needed: Considered to distinguish the cognitive-performance objective from separate event/functional and biochemical outcomes. - Application exceptions: Do not unconditionally require a dementia-conversion trial for the global-score question. - Remaining uncertainty: No judgment of absence of events or absence of an effect on events is made either. - Referenced methods: 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 - Related sources: S10 ### N37 · Were AE, SAE, discontinuations, deaths and observation periods by arm verified? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: 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. - Reason for missing information: Do not use the existing inference of 60 participants per arm as a safety denominator. - Required materials and conditions: Definitions, collection, participant/event counts, denominators and follow-up periods for AE/SAE and discontinuations/deaths by arm - Materials to obtain first: Definitions, collection, participant/event counts, denominators and follow-up periods for AE/SAE and discontinuations/deaths by arm - Further research: Define and systematically collect adverse events, and report exposed participants, participant/event counts, duration and discontinuations by arm separately from efficacy denominators. - Conditions for verification: Distinguish the core candidate's actual harms counts from the unverified scope. - Why this condition is needed: Required to avoid turning unreported adverse events into 0 events or established safety. - Application exceptions: Retain gaps in harms data despite unverified efficacy data, and limit the nonreporting statement to the original abstract's scope. - Remaining uncertainty: Do not use the existing inference of 60 participants per arm as a safety denominator. - Referenced methods: 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 - Related sources: S01, S03 ### N38 · Was the absence of an established UL interpreted as unlimited safety or efficacy in MCI? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The official context is recorded in the retained material, but individual exposure and long-term safety in the core candidate are unverified. - Reason for missing information: The ODS original was not read in this exercise, and no personal dosing or medication-discontinuation instructions are created. - Required materials and conditions: Original ODS context for UL/medications and safety exposure data by population/formulation - Materials to obtain first: Original ODS context for UL/medications and safety exposure data by population/formulation - Further research: Design observations of long-term/high-dose exposure and safety by population/formulation, and track concomitant medications and B12 status. - Conditions for verification: Retain the limited role of the absence of an established UL and of the metformin/gastric-acid-inhibitor context. - Why this condition is needed: Considered to avoid extending nutritional information to clinical efficacy or a guarantee of overall safety. - Application exceptions: Distinguish historical descriptions of official documents from direct reading in this exercise. - Remaining uncertainty: The ODS original was not read in this exercise, and no personal dosing or medication-discontinuation instructions are created. - Referenced methods: 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 - Related sources: S14 ### N39 · Was the MHRA warning transferred to the incidence for another B12 chemical form? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The scope to which the warning applies is preserved, but the core monotherapy arm's chemical form and comparative incidence are unverified. - Reason for missing information: The regulatory original was not opened in this exercise, and no quantitative risk for all B12 is created. - Required materials and conditions: Original hydroxocobalamin/cyanocobalamin warning and exposure/population/event denominators - Materials to obtain first: Original hydroxocobalamin/cyanocobalamin warning and exposure/population/event denominators - Further research: Develop appropriate observational material tracking chemical-form-specific exposure, sensitivity-event definitions and denominators. - Conditions for verification: Preserve the sensitivity warning only for the specified chemical forms, without estimating comparative risks for other chemical forms. - Why this condition is needed: Required to distinguish the warning's actual chemical-form scope from event incidence. - Application exceptions: General cobalt-allergy prevalence is not an adverse-event rate during B12 treatment. - Remaining uncertainty: The regulatory original was not opened in this exercise, and no quantitative risk for all B12 is created. - Referenced methods: 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 - Related sources: S15 ### N40 · Was cyanocobalamin injection labeling repurposed as risk in oral treatment for MCI? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: The labeling has a narrowly attributable scope, but event counts/risks for oral monotherapy in MCI are unverified. - Reason for missing information: The DailyMed original was not read in this exercise, and the labeling scope is not expanded. - Required materials and conditions: The actual injectable product's labeling warnings about Leber disease and hypokalemia during intensive treatment of severe anemia, and direct oral safety data - Materials to obtain first: The actual injectable product's labeling warnings about Leber disease and hypokalemia during intensive treatment of severe anemia, and direct oral safety data - Further research: Separately observe safety counts in the oral MCI population by formulation, exposure and medical history, distinguishing them from intensive injectable-treatment data. - Conditions for verification: Distinguish the population/route in injection labeling from the current oral question. - Why this condition is needed: Required to avoid transferring labeling with a different route, chemical form and intensive-treatment population to incidence in an oral trial. - Application exceptions: Retain the labeling language without interpreting it as incidence for another chemical form or oral treatment in MCI. - Remaining uncertainty: The DailyMed original was not read in this exercise, and the labeling scope is not expanded. - Referenced methods: 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 - Related sources: S16 ### N41 · Were harms from high doses or in special populations beyond 6 months verified? Verification status: Unverified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Population-specific and duration-specific safety material and denominators were not verified. - Reason for missing information: Do not turn unverified information into absence of risk or a quantitative harmful effect. - Required materials and conditions: Exposure and follow-up for long-term/high-dose use, pregnancy/lactation/children and liver/kidney status - Materials to obtain first: Exposure and follow-up for long-term/high-dose use, pregnancy/lactation/children and liver/kidney status - Further research: Systematically collect population-specific harms in exposure registries/observational material with sufficient follow-up, and distinguish rare-event reports from incidence. - Conditions for verification: Distinguish the direct observation period from the scope of unverified special populations. - Why this condition is needed: Required to avoid extending material from a limited duration/population to overall safety. - Application exceptions: Do not require every rare-harm study for the current cognitive-score question. - Remaining uncertainty: Do not turn unverified information into absence of risk or a quantitative harmful effect. - Referenced methods: 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 - Related sources: S01, S03 ### N42 · Were unverified Ma funding and disclosures in adjacent trials/reviews distinguished? Verification status: Partly verified Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Disclosures from some adjacent material are preserved, but verification of the core monotherapy trial's independence remains outstanding. - Reason for missing information: Do not transfer another source's disclosures to Ma or create a new independence score. - Required materials and conditions: Original disclosures of Ma funding, product provision, employment/patents/interests and sponsor roles - Materials to obtain first: Original disclosures of Ma funding, product provision, employment/patents/interests and sponsor roles - Further research: Transparently report the core trial's funding, product provision and author relationships, and separately assess replication criteria for unique trials. - Conditions for verification: Distinguish unverified core material from the actual scope of VITACOG/S13 disclosures. - Why this condition is needed: Required to avoid transferring disclosures from adjacent material as verification of the core trial's funding or independence. - Application exceptions: Do not automatically discard results because industry-related support exists, or treat a declaration of no sponsor role as establishing absence of bias. - Remaining uncertainty: Do not transfer another source's disclosures to Ma or create a new independence score. - Referenced methods: 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 - Related sources: S01, S03, S10, S13 ### N43 · Was summary reading separated from historical/current access for the 21 sources? Verification status: Met Reading scope: Summary read: the exact locations in the current local stored summaries were actually read. External materials were not accessed or read in this exercise. - Current findings: 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. - Why unverified: Reading the current local stored summaries was separated by material type from external access not attempted/material not read in this exercise. - Reason for missing information: The complete original papers, protocols/SAPs and current publication/public-availability status were not newly verified. - Required materials and conditions: Bibliographic/original URLs by material type, historical access level, access date and exact locations actually read in this exercise - Materials to obtain first: Bibliographic/original URLs by material type, historical access level, access date and exact locations actually read in this exercise - Further research: When direct material is subsequently obtained, record type, acquisition/access/reading/date and exact location as separate events, and review linked rows again. - Conditions for verification: Record reading of the current stored summaries, external access not attempted/material not read, and historical descriptions separately. - Why this condition is needed: 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 exceptions: If there is no actual access-date field, leave it blank and do not substitute verified_date for the access date. - Remaining uncertainty: The complete original papers, protocols/SAPs and current publication/public-availability status were not newly verified. - Referenced methods: 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 - Related sources: ## Evidence and sources ### S01 Ma F et al. Effects of Folic Acid and Vitamin B12, Alone and in Combination… Curr Alzheimer Res. 2019;16(7):622–632. [Source](https://www.eurekaselect.com/article/99971) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Paper abstract | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S02 Ma2019 PubMed bibliographic record [Source](https://pubmed.ncbi.nlm.nih.gov/31345146/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full bibliographic web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S03 ChiCTR-ROC-16008305 registry access attempt [Source](https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-ROC-16008305) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full registration web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full protocol and statistical analysis plan | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S04 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. [Source](https://pubmed.ncbi.nlm.nih.gov/27823800/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full bibliographic web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S05 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. [Source](https://research.cuhk.edu.hk/en/publications/a-randomized-placebo-controlled-trial-of-using-b-vitamins-to-prev-2/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Paper abstract | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S06 Zhou et al. Vitamin B12 supplementation improves cognitive function in middle aged and elderly patients with cognitive impairment. Nutr Hosp. 2023;40(4). [Source](https://scielo.isciii.es/scielo.php?pid=S0212-16112023000500007&script=sci_arttext) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S07 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. [Source](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) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S08 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. [Source](https://pubmed.ncbi.nlm.nih.gov/26135351/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full bibliographic web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S09 Jatoi S et al. Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia. Cureus. 2020;12(2):e6976. [Source](https://pubmed.ncbi.nlm.nih.gov/32206454/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full bibliographic web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S10 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. [Source](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S11 Lauer AA et al. Mechanistic Link between Vitamin B12 and Alzheimer’s Disease. Biomolecules. 2022;12:129. [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC8774227/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full review article text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S12 Markun S et al. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue. Nutrients. 2021;13:923. [Source](https://www.mdpi.com/2072-6643/13/3/923) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full bibliographic/search web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full review article text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S13 Elgar K. Vitamin B12: A Review of Clinical Use and Efficacy. Nutritional Medicine Journal. 2022;1(3):9–25. [Source](https://www.nmi.health/vitamin-b12-a-review-of-clinical-use-and-efficacy/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full review article text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S14 NIH Office of Dietary Supplements. Vitamin B12: Health Professional Fact Sheet. [Source](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S15 MHRA. Vitamin B12 (hydroxocobalamin, cyanocobalamin): known cobalt allergy and sensitivity reactions. 18 December 2023. [Source](https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S16 DailyMed. CYANOCOBALAMIN injection labeling. [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S17 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. [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC12280771/) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S18 NCT02457507 registry landing page [Source](https://clinicaltrials.gov/study/NCT02457507) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full registration web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full protocol and statistical analysis plan | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S19 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. [Source](https://www.mdpi.com/1661-3821/6/2/35) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full bibliographic web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S20 Berg J et al. Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis. 2025. [Source](https://pubmed.ncbi.nlm.nih.gov/?term=%22Efficacy+of+B+Vitamin+Supplementation+on+Global+Cognitive+Function%22) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full bibliographic/search web document | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full review article text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ### S21 Ma2019 author abstract on ResearchGate [Source](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) Materials actually read: The relevant summaries and bibliographic records in the stored manuscript were checked. The linked external original materials were not read in this exercise. Findings recorded in the summary: 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. Record 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. 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Paper abstract | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | | Full paper text | Currently unverified (no external lookup) | Access not attempted | Not read | 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. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations in the intervention. · 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. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported. · 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. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting. · 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. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · 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. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence. · 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. ## What the statuses mean - 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. ## Change history 2026-11-05 · Public page/materials 1.0. 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. ## Material-specific source addresses - [S01-M1 · Paper abstract](https://www.eurekaselect.com/article/99971) - S01-M2 · Full paper text: Material URL unverified; external material unread. - [S02-M1 · Full bibliographic web document](https://pubmed.ncbi.nlm.nih.gov/31345146/) - S02-M2 · Full paper text: Material URL unverified; external material unread. - [S03-M1 · Full registration web document](https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-ROC-16008305) - S03-M2 · Full protocol and statistical analysis plan: Material URL unverified; external material unread. - [S04-M1 · Full bibliographic web document](https://pubmed.ncbi.nlm.nih.gov/27823800/) - S04-M2 · Full paper text: Material URL unverified; external material unread. - [S05-M1 · Paper abstract](https://research.cuhk.edu.hk/en/publications/a-randomized-placebo-controlled-trial-of-using-b-vitamins-to-prev-2/) - S05-M2 · Full paper text: Material URL unverified; external material unread. - [S06-M1 · Full paper text](https://scielo.isciii.es/scielo.php?pid=S0212-16112023000500007&script=sci_arttext) - [S07-M1 · Full paper text](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) - [S08-M1 · Full bibliographic web document](https://pubmed.ncbi.nlm.nih.gov/26135351/) - S08-M2 · Full paper text: Material URL unverified; external material unread. - [S09-M1 · Full bibliographic web document](https://pubmed.ncbi.nlm.nih.gov/32206454/) - S09-M2 · Full paper text: Material URL unverified; external material unread. - [S10-M1 · Full paper text](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244) - [S11-M1 · Full review article text](https://pmc.ncbi.nlm.nih.gov/articles/PMC8774227/) - [S12-M1 · Full bibliographic/search web document](https://www.mdpi.com/2072-6643/13/3/923) - S12-M2 · Full review article text: Material URL unverified; external material unread. - [S13-M1 · Full review article text](https://www.nmi.health/vitamin-b12-a-review-of-clinical-use-and-efficacy/) - [S14-M1 · Full official web document](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/) - [S15-M1 · Full official web document](https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions) - [S16-M1 · Full official web document](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6) - [S17-M1 · Full paper text](https://pmc.ncbi.nlm.nih.gov/articles/PMC12280771/) - [S18-M1 · Full registration web document](https://clinicaltrials.gov/study/NCT02457507) - S18-M2 · Full protocol and statistical analysis plan: Material URL unverified; external material unread. - [S19-M1 · Full bibliographic web document](https://www.mdpi.com/1661-3821/6/2/35) - S19-M2 · Full paper text: Material URL unverified; external material unread. - [S20-M1 · Full bibliographic/search web document](https://pubmed.ncbi.nlm.nih.gov/?term=%22Efficacy+of+B+Vitamin+Supplementation+on+Global+Cognitive+Function%22) - S20-M2 · Full review article text: Material URL unverified; external material unread. - [S21-M1 · Paper abstract](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) - S21-M2 · Full paper text: Material URL unverified; external material unread.