Baseline Vitamin B12 as a Prognostic Marker of Cognitive Progression in Mild Cognitive Impairment: A Systematic Review

Beatriz De Faria Sousa; Jhon Ostanin; Helena Miranda

Abstract:

Introduction:
Vitamin B12 deficiency is frequently evaluated in patients with cognitive impairment, yet its prognostic value for disease progression among individuals with mild cognitive impairment (MCI) remains uncertain. While vitamin B12 is routinely measured in memory clinics, it is unclear whether baseline levels meaningfully predict longitudinal cognitive decline or conversion to dementia within the Alzheimer’s disease spectrum.

Methods:
This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Embase, PsycINFO, and Scopus were searched for longitudinal human studies published between 2005 and 2025. Eligible studies enrolled adults with clinician-diagnosed MCI at baseline, measured baseline serum vitamin B12, and reported longitudinal outcomes, including cognitive decline on standardized neuropsychological tests or conversion from MCI to dementia. Screening and full-text eligibility assessment were performed using Covidence. Due to heterogeneity in study design, outcomes, and analytic methods, findings were synthesized narratively.

Results:
Of 330 records identified, 24 full-text articles were assessed, and five longitudinal cohort studies met inclusion criteria. Sample sizes ranged from 49 to 422 participants, with follow-up durations between 24 months and 3.5 years. Findings were inconsistent. Two studies reported associations between lower baseline vitamin B12 levels and greater cognitive decline; however, these associations were attenuated after multivariable adjustment and derived from cohorts that included mixed MCI and early Alzheimer’s disease populations. Three studies, including the largest and most methodologically robust cohort, found no significant association between baseline vitamin B12 levels and cognitive decline or conversion to dementia.

Conclusions:
Current longitudinal evidence does not consistently support baseline vitamin B12 as an independent prognostic marker of cognitive progression in MCI. These findings suggest that routine measurement of serum vitamin B12 alone may have limited value for risk stratification, highlighting the need for future studies using functionally sensitive biomarkers of vitamin B12 status and standardized progression endpoints.