The Association Between Folate and Alzheimer's Disease: A Systematic Review and Meta-Analysis

source extracted confidence: high 2026-04-09

The Association Between Folate and Alzheimer's Disease: A Systematic Review and Meta-Analysis

Zhang et al., 2021 | Front Neurosci | Systematic Review

Citation

Zhang Xiaohong, Bao Guangyi, ... Wu Yili. The Association Between Folate and Alzheimer's Disease: A Systematic Review and Meta-Analysis. Front Neurosci. 2021;15:661198. doi:10.3389/fnins.2021.661198

Abstract

Alzheimer's disease (AD) is the most common type of neurodegenerative disease leading to dementia in the elderly. Increasing evidence indicates that folate plays an important role in the pathogenesis of AD. To investigate the role of folate deficiency/possible deficiency in the risk of AD and the benefical effect of sufficient folate intake on the prevention of AD, a systematic review and meta-analysis were performed. The Web of Science, PubMed, CENTRAL, EBSCO, CNKI, CQVIP, and Wanfang databases were searched. The analysis of cross-sectional studies showed that the standardized mean difference (SMD) was -0.60 (95% confidence interval (CI): -0.65, -0.55), indicating that plasma/serum folate level is lower in AD patients than that in controls. Moreover, the combined odds ratio (OR) of case-control studies was 0.96 (95% CI: 0.93, 0.99), while the combined ORs were 0.86 (95% CI: 0.46, 1.26) and 1.94 (95% CI: 1.02, 2.86) in populations with normal levels of folate (≥13.5 nmol/L) and folate deficiency/possible deficiency (<13.5 nmol/L), respectively. In addition, the risk ratio (RR) of the cohort studies was 1.88 (95% CI: 1.20, 2.57) in populations with folate deficiency/possible deficiency. Furthermore, when the intake of folate was equal to or higher than the recommended daily allowance, the combined RR and hazard ratio (HR) were 0.44 (95% CI: 0.18, 0.71) and 0.76 (95% CI: 0.52, 0.99), respectively. These results indicate that folate deficiency/possible deficiency increases the risk for AD, while sufficient intake of folate is a protective factor against AD.

Key Findings

These results indicate that folate deficiency/possible deficiency increases the risk for AD, while sufficient intake of folate is a protective factor against AD.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition deficiency

MeSH Terms

  • No MeSH terms indexed

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Systematic Review, Journal Article
  • Vertical: folate

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09