Body mass index and risk of dementia: Analysis of individual-level data from 1.3 million individuals

INTRODUCTION: Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects. METHODS: We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis. RESULTS: Hazard ratios per 5-kg/m(2) increase in BMI for dementia were 0.71 (95% confidence interval = 0.66–0.77), 0.94 (0.89–0.99), and 1.16 (1.05–1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis. CONCLUSIONS: The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short.