Cognitive Function in an Elderly Population: Interaction Between Vitamin B12 Status, Depression, and Apolipoprotein E ε4: The Hordaland Homocysteine Study

Objective: To investigate the cross-sectional relation between metabolic markers of vitamin B-12 status and cognitive performance, and possible effect modification by the presence of depression and apolipoprotein E (ApoE) epsilon 4. Methods: This is a population-based study of 1935 participants, aged 71 to 74 years, from Norway. Participants were administered a cognitive test battery, and vitamin B-12 status was assessed by measurements of plasma vitamin B-12, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine. Results: The geometric mean (95% confidence interval) for vitamin B-12 was 348 pM (341-354), whereas 5.9% of participants had vitamin B-12 levels lower than 200 pM. In linear regression analyses, holoTC (p = .039) and the holoTC/vitamin B-12 ratio (P = .013) were positively related, whereas MMA (p = .010) was inversely related, to global cognition, after adjustment for sex, education, ApoE status, plasma creatinine, and history of diabetes, cardiovascular disease, hypertension, and depression. Among those positive for ApoE epsilon 4, but not among those without the 84 allele, plasma vitamin B-12 was positively associated with global cognition (p = .015), whereas MMA was inversely related to global cognition (p = .036) and executive function (p = .014). In participants with depression, MMA was inversely associated with global cognition (p < .001) and episodic memory (p = .001). Conclusions: Among the well-nourished elderly, low vitamin B-12 status is associated with cognitive deficit, particularly in those with the ApoE epsilon 4 allele or with depression.