A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people

SummaryIntroductionWhether homocysteine lowering by B vitamins can reduce cognitive decline in Alzheimer disease and vascular dementia patients is unclear.Methods and materials140 subjects with mild to moderate Alzheimer disease or vascular dementia were randomly assigned to take 1 mg of methylcobalamin and 5 mg of folic acid, or placebo once daily for 24 months. The primary outcome was Mattis dementia rating scale (MDRS). Secondary outcomes were MDRS domain scores, neuropsychiatric inventory and Cornell scale for depression in dementia. Measurements were performed at baseline and every six months during the study. Fasting plasma tHCY concentrations were measured at baseline and month 18.ResultsTrial groups were well matched in baseline characteristics. The average plasma tHCY concentration of subjects was 14.1 ± 3.8 μmol/L. 80% of subjects completed the trial. The supplement group had average plasma tHCY reduced to 9.3 ± 2.7 μmol/L. There was no significant group difference in changes in any of the neuropsychological scores, but among those with elevated plasma tHCY (>13 μmol/L), the decline in MDRS (construction domain) was significantly smaller in the supplement group (median 0 versus 2 points in placebo group, P = 0.003).ConclusionHomocysteine lowering in dementia patients did not significantly reduce global cognitive decline.