Blood and CSF Homocysteine Levels in Alzheimer's Disease: A Meta-Analysis and Meta-Regression of Case-Control Studies.
Level 4 - case-series / case-control
Systematic review and meta-analysis of case-control studies
PubMed 36276430 · doi:10.2147/NDT.S383654
What was done
A systematic review and meta-analysis of PubMed and Embase databases evaluated blood and cerebrospinal fluid (CSF) homocysteine (Hcy) levels in Alzheimer's disease (AD) patients compared to healthy controls. Study quality was assessed with the Newcastle-Ottawa Scale. Effect sizes were calculated as ratio of mean (RoM) concentrations. Random-effects meta-regression was conducted to examine associations with blood folate, blood vitamin B12, and Mini-Mental Status Examination (MMSE) scores.
What was found
Across 35 studies including 2,172 AD patients and 2,289 controls, AD patients had significantly higher blood Hcy than controls (RoM 1.32, 95% CI 1.25-1.40, p < 0.001; I2 = 81.4%, p < 0.001). CSF Hcy was not significantly different between AD patients and controls (RoM 1.12, 95% CI 0.90-1.39, p = 0.293; I2 = 69.4%, p = 0.02). Meta-regression revealed an inverse correlation between blood levels of Hcy and folate (p = 0.006), but no significant association with blood vitamin B12 or MMSE scores.
Why it matters
This review demonstrates an approximate one-third increase in peripheral blood homocysteine in AD patients linked specifically to reduced folate levels rather than vitamin B12 or cognitive impairment severity. It also shows that peripheral blood elevations are not statistically reflected in CSF homocysteine concentrations.
Limits
The underlying evidence consists entirely of case-control studies, which prevents causal inference. There was substantial heterogeneity across studies for both blood and CSF analyses. The abstract does not report the subset sample size or number of studies contributing specifically to the CSF analysis.
Cited by
- supports Elevated homocysteine is associated with brain dysfunction and dementia.