Background and objective: Elevated homocysteine has been associated with higher prevalence of cerebral white matter lesions and infarcts, and worse cognitive performance. This raises the question whether factors involved in homocysteine metabolism, such as vitamin B12, are also related to these outcomes. We examined the association of several markers of vitamin B12 status with cerebral white matter lesions, infarcts, and cognition.
Methods: We evaluated the association of plasma concentrations of vitamin B12, methylmalonic acid, holotranscobalamin, and transcobalamin saturation with cerebral white matter lesions and infarcts at baseline and cognition at baseline and during follow-up among 1,019 non-demented elderly participants of the population-based Rotterdam Scan Study. Analyses were adjusted for several potential confounders, including homocysteine and folate concentration.
Results: Poorer vitamin B12 status was significantly associated with greater severity of white matter lesions, in particular periventricular white matter lesions, in a concentration-related manner. Adjustment for common vascular risk factors (including blood pressure, smoking, diabetes, and intima media thickness) did not alter the associations. Adjustment for homocysteine and folate modestly weakened the associations. No association was observed for any of the studied markers of vitamin B12 status with presence of brain infarcts and baseline cognition or cognitive decline during follow up.
Conclusions: Our results indicate that vitamin B12 status in the normal range is associated with severity of white matter lesions, especially periventricular lesions. Given the absence of an association with cerebral infarcts, we hypothesize that this association is explained by effects on myelin integrity in the brain rather than through vascular mechanisms.