Invited Commentary: Body Mass Index and Risk of Dementia-Potential Explanations for Life-Course Differences in Risk Estimates and Future Research Directions.

The relationship between body mass index (BMI) and health outcomes of older adults, including dementia, remains controversial. Many studies find inverse associations between BMI and dementia among older adults, while in other studies high BMI in midlife is associated with increased dementia risk. In this issue, Li et al. (Am J Epidemiol. 2021;190(12):2503-2510) examine BMI from mid- to late life and risk of dementia using the extensive follow-up of the Framingham Offspring Study. They found changing trends in the association between BMI and dementia from a positive association for midlife (ages 40-49) to an inverse trend in late life. Their work demonstrates the importance of studying dementia risk factors across the life course. Midlife obesity might be an important modifiable risk factor for dementia. However, because incipient dementia can lead to weight loss, reverse causation remains a key source of bias that could explain an inverse trend between BMI and dementia in older ages. The extent of other biases, including unmeasured confounding, inaccuracy of BMI as a measure for adiposity, or selective survival, are also unclear. Triangulating evidence on body composition and dementia risk could lead to better targets for dementia intervention, but future work will need to evaluate specific pathways.