Elevated homocysteine levels may not be a risk factor for cognitive decline in older patients, despite previous evidence, reported Jennifer A. McMahon, Ph.D.
She and her colleagues at the University of Otago, New Zealand, conducted a 2-year randomized, double-blind, placebo-controlled trial to assess the effect of homocysteine lowering on the cognitive abilities of people aged older than 65 years through neuropsychological tests (N. Engl. J. Med. 2006;354:2764–72).
The researchers found that the reduction of plasma homocysteine in the studied elderly population was not associated with significant differences from placebo in various measures of cognitive ability.
A total of 253 participants (mean age 74 years) completed the study. To be enrolled, the patients were required to have a fasting homocysteine level of at least 13 μmol/L and a normal plasma creatinine level; to be free of suspected dementia, current depression treatment, history of stroke/transient ischemic attack, and diabetes; and to not be taking B-vitamin supplements or medications that can affect folate metabolism.
The investigators then gave the treatment group (127 patients) a daily supplement comprising 1,000 mcg folate, 500 mcg B12, and 10 mg B6. The mean homocysteine level, with this regimen, was 4.36 mol/L lower in the vitamin group than in the placebo group (126 patients), over the course of the study.
But when the cognitive tests–the Mini-Mental State Examination, the Wechsler Paragraph Recall test, and others–were administered at 1 and 2 years and adjustment for sex and education, differences between the two groups were not significant–except for those on the Reitan Trail Making Test.
On that test, participants in the vitamin group actually performed worse (took longer to complete the test) than did the placebo group (P = .007). The investigators remarked that this might be a chance finding, however.
Moreover, when the investigators combined the results of all the tests using a generalized estimating equation that was adjusted for baseline value, gender, and education, the resulting score for the vitamin group was lower than that of the placebo group–a finding that the investigators noted contradicts “the weight of a substantial body of observational evidence.”
However, this difference barely reached significance (P = .05). Baseline characteristics of the patients were similar.