Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 20838622 · doi:10.1371/journal.pone.0012244
What was done
In a single-center, randomized, double-blind, placebo-controlled trial (VITACOG), 271 individuals over 70 years old with mild cognitive impairment were randomized to receive high-dose B vitamins (0.8 mg/d folic acid, 0.5 mg/d vitamin B12, and 20 mg/d vitamin B6) or placebo daily for 24 months. A subset of 187 participants volunteered for serial cranial volumetric MRI scans at baseline and trial completion to evaluate the rate of whole-brain atrophy.
What was found
A total of 168 participants completed the MRI protocol (85 active treatment, 83 placebo). The mean annual rate of brain atrophy was 0.76% (95% CI, 0.63 to 0.90) in the active group compared with 1.08% (95% CI, 0.94 to 1.22) in the placebo group (P = 0.001). Among participants with baseline homocysteine >13 umol/L, the atrophy rate was 53% lower with active treatment (P = 0.001). A greater atrophy rate correlated with lower final cognitive test scores. Serious adverse events did not differ significantly between groups.
Why it matters
Homocysteine-lowering B-vitamin therapy can slow structural brain atrophy in elderly individuals with mild cognitive impairment, particularly in those with higher baseline homocysteine levels.
Limits
The primary imaging outcome was assessed only in a self-selected subset of 168 completers rather than the entire enrolled sample. The trial was conducted at a single center and evaluated brain atrophy rather than conversion rates to clinical Alzheimer's disease.
Cited by
- partial Elevated homocysteine levels correlate with more rapid cerebral gray matter and hippocampal volume loss, and normalizing homocysteine halts this volume decline.