Mid- to Late-Life Body Mass Index and Dementia Risk

38 Years of Follow-up of the Framingham Study

Jinlei Li; Prajakta Joshi; Ting Fang Alvin Ang; Chunyu Liu; Sanford Auerbach; Sherral Devine; Rhoda Au


Am J Epidemiol. 2021;190(12):2503-2510. 

In This Article

Abstract and Introduction


Growing evidence relates body mass index (BMI) to poorer health outcomes; however, results across studies associating BMI and dementia are conflicting. A total of 3,632 Framingham Offspring participants aged 20 to 60 years at their second health examination (1979–1983) were included in this study, with 190 cases of incident dementia identified by 2017. Cox proportional hazards regression models were fitted to investigate the association of BMI at each of their 8 exams as a baseline for dementia risk and the associations between obesity and dementia across age groups. Spline models were fitted to investigate nonlinear associations between BMI and dementia. Each 1-unit increase in BMI at ages 40–49 years was associated with higher risk of dementia, but with lower risk after age 70 years. Obesity at ages 40–49 years was associated with higher risk of dementia. Overall, the relationship between BMI and dementia risk was heterogeneous across the adult age range. Monitoring BMI at different ages might mediate risk for dementia across an individual's lifetime.


With the rapid increase in the aging population, there has been an escalation in the number of people living with dementia worldwide. The number of people living with dementia worldwide is currently estimated at 50 million and will almost triple by 2050.[1] Currently, there are no effective disease-modifying therapies; thus, there has been an increasing call for a focus on dementia prevention as the best strategy for attenuating disease incidence.[2] Body mass index (BMI), as a modifiable risk factor, has been related to various poorer health outcomes,[3] but its specific relationship to dementia risk remains a matter of debate.

Observational studies have reported positive, null, and inverse associations between BMI and dementia risk:[4] Evidence from longitudinal prospective studies and meta-analyses suggests that high BMI or obesity in midlife is associated with an increased risk of dementia.[5–12] However, the hypothesis of the causal link between obesity and dementia has been challenged by some recent findings.[13] A study of 2 million adults showed lower rates of dementia in those who are obese (BMI, weight (kg)/height (m)2, of >40) and progressively decreasing risk with increasing obesity.[14] This new study challenges the presumed direction of the association found from previous meta-analyses due to the large number of participants.[13] Results on the association between late life BMI and dementia is more mixed.[15,16] Some studies report that being underweight or having a normal BMI in late life is associated with an increased risk of dementia,[17–20] while others indicate an opposite relationship.[21,22]

Factors influencing the heterogeneity of study results might include age at assessment of BMI and years of follow-up for incident diagnosis. In this study, we used data from the Framingham Offspring Cohort, which includes serial assessments of BMI and prospective follow-up for incident dementia over 38 years to evaluate dementia risk associated with BMI from mid- to late life.