title: Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression.
abstract: OBJECTIVE
  [corrected] High homocysteine (Hct) has been causatively linked to Alzheimer disease (AD) and vascular dementia (VaD) in old age, but research methodologies and outcome measures are heterogeneous. It remains unclear whether the findings can be generalized across studies.
  
  
  METHODS
  Random-effects meta-analyses were conducted on studies examining the relationship between Hct level and risk of developing dementia/cognitive decline between comparison groups. Meta-regression identified patient- and trial-related factors, which may contribute to heterogeneity.
  
  
  RESULTS
  Seventeen relevant studies (6,122 participants; 13 cross-sectional and fourprospective studies) were included. Compared with controls, Hct was significantly elevated in AD (pooled standardized mean difference [SMD]: 0.59; 95% confidence interval [CI]: 0.38-0.80; significant heterogeneity: τ = 0.105) and VaD (pooled SMD: 1.30; 95% CI: 0.75-1.84; significant heterogeneity: τ = 0.378). Meta-regression identified mean age as significant moderator for AD versus controls and mean age and mean folate levels as significant moderators for VaD versus controls. Hct was significantly higher in VaD relative to AD (pooled SMD: 0.48; 95% CI: 0.23-0.73; moderately significant heterogeneity: τ = 0.076); proportion of men and mean folate levels were significant moderators. High-Hct level was not associated with risk of developing dementia in prospective studies (pooled odds ratio: 1.34; 95% CI: 0.94-1.91, nonsignificant heterogeneity: τ = 0.048).
  
  
  CONCLUSIONS
  Individuals with AD and VaD have higher Hct levels than controls; however, a causal relationship between high-Hct level and risk of developing dementia is not supported. More prospective studies and randomized controlled trials are required to test the therapeutic benefits of lowering Hct levels.
authors.affiliation: Department of Psychological Medicine, Yong Loo Lin School of Medicine, Singapore. pcmrhcm@nus.edu.sg
authors.forename: Roger C M
authors.initials: RC
authors.lastname: Ho
authors.forename: Mike W L
authors.initials: MW
authors.lastname: Cheung
authors.forename: Erin
authors.initials: E
authors.lastname: Fu
authors.forename: Hlaing H
authors.initials: HH
authors.lastname: Win
authors.forename: Min Htet
authors.initials: MH
authors.lastname: Zaw
authors.forename: Amanda
authors.initials: A
authors.lastname: Ng
authors.forename: Anselm
authors.initials: A
authors.lastname: Mak
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis*; D003704:Dementia / Q000175:diagnosis*; D015140:Dementia, Vascular / Q000175:diagnosis*; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012044:Regression Analysis; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12