The role of B vitamins in preventing and treating cognitive impairment and decline.

Many epidemiologic studies have considered whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease, which was extended to Alzheimer's disease when a link between vascular dementia and Alzheimer's disease was discovered. Hcy could cause cognitive impairment via direct neurotoxicity. However, decreased remethylation of Hcy to methionine might also compromise cognitive function by means other than mere Hcy lowering. Folate and vitamin B-12 participate in Hcy remethylation and largely determine Hcy status. Consequently, much of the relevant research has focused on these 2 B vitamins. The many subtly different hypotheses that investigators have addressed by attempting to link several B-vitamin status indicators to diverse cognition-related outcomes have created a confusing body of conflicting studies that seems to defy summarization. Nevertheless, themes are discernible that aid interpretation, foster hypothesis generation, and inform future study design. For example, despite a shared metabolic pathway, Hcy, vitamin B-12, and folate are differently related to specific cognitive outcomes. Although consistency of findings across studies is often touted as essential to distinguishing causal from coincidental relationships, discrepancies among study findings can be even more informative.