Objective:

Our objective was to examine associations among plasma homocysteine concentrations (tHcy), the tHcy-cofactors (folate, vitamins B 6 and B 12 ), and multiple domains of cognitive performance, with statistical adjustment for possible confounds, including cardiovascular disease risk factors (CVD-RF) and cardiovascular disease (CVD).

Methods:

Subjects were 812 participants (58% women) of the Maine-Syracuse study who were free of dementia and stroke. Employing a cross-sectional design and multiple regression analyses, fasting concentrations of tHcy and its vitamin cofactors (folate, B 6 , and B 12 ) were related to multiple domains of cognitive performance.

Results:

With adjustment for age, education, gender, ethnicity, and the vitamins, tHcy was inversely associated with visual-spatial organization, working memory, scanning-tracking, and abstract reasoning. The same results were found with adjustment for age, education, gender, ethnicity, CVD-RF, and CVD. Vitamin cofactors were positively related to cognitive performance, but with adjustment for CVD-RF and CVD, only vitamin B 6 was related to multiple cognitive domains.

Conclusions:

The inverse association of tHcy with multiple domains of cognitive functioning is not necessarily dependent on vitamin levels, vitamin deficiency, prevalent CVD risk factors, and manifest CVD. Serum folate, serum B 12 , and plasma B 6 vitamin concentrations are positively associated with cognitive performance. Investigation of other possible mechanisms (e.g., tHcy neurotoxicity) mediating tHcy associations with cognitive performance is important, as are clinical trials examining the efficacy of folate, vitamin B 6 , and vitamin B 12 for maintenance of cognitive functioning.