Challenges of long-term nutrition intervention studies on cognition: discordance between observational and intervention studies of vitamin B12 and cognition

Conducting long-term nutrition intervention studies on cognition can be challenging. The gaps in current methodology are addressed via a case study of the relationship between vitamin B12 and cognition in people aged 60 and older. There is robust evidence from many observational studies, both cross-sectional and longitudinal, showing that a deficit of the vitamin is associated with poor or declining cognition in this age group, but supplementation of the vitamin in trials does not bring about improved cognition. The evidence from observational studies as well as clinical trials is reviewed here, and the potential difficulties in conducting long-term nutritional intervention studies in this area are highlighted.