Abstract DP335: Association of Midlife and Late-life Obesity and Adiposity Measures with Late-life Brain Amyloid Deposition: An Atherosclerosis Risk in Communities Study

Introduction: In many people with Alzheimer’s disease (AD), vascular and metabolic disease are common and may contribute to disease pathogenesis. Obesity, defined as a body mass index (BMI) >= 30, has differential associations with brain health depending on when in the life course it is measured. It appears to be a risk factor when measured in midlife but not in late-life. Most current studies only use BMI to measure obesity, which does not differentiate fat distribution, a factor that can influence disease risk. In the Atherosclerosis Risk in Communities (ARIC) study, we investigated the association of obesity (measured using BMI, waist circumference (WC), and waist-to-hip ratio (WHR)) in midlife and late-life with late-life brain amyloid deposition on florbetapir PET as a marker of AD pathogenesis in adults without dementia. Methods: Participants were followed from 1987-1989 (visit 1; midlife, ages 45-64) and received a PET scan at a late-life visit (between visit 5 (2011-2013) and visit 11 (2025); ages 67-95). Our analysis included all participants with a PET scan who were dementia-free at time of scan. The measures of obesity were categorical BMI, sex-specific WC, and sex-specific WHR measured at midlife and late-life. Logistic regressions assessed the relationship between obesity measures and amyloid positivity (standardized uptake value ratio >1.2) in separate models. Models were adjusted for demographics and vascular risk factors. Results: In 803 participants meeting inclusion criteria, 438 were amyloid negative and 365 were amyloid positive. In midlife, those with obese, but not overweight, BMI had a 70% increase in odds of amyloid positivity compared to those with normal BMI (Table 1). In late life, neither overweight nor obese BMI was associated with amyloid positivity (Table 2). No relationship between categorical WC or WHR and amyloid positivity was seen at visit 1 or 5. Conclusion: Midlife obesity is significantly associated with increased odds of amyloid positivity in late-life in adults without dementia, but no association is seen with late-life obesity, overweight BMI at midlife or late-life, or WC or WHR. These findings highlight the importance of midlife as a critical period influencing future brain health and suggest BMI may be a more useful clinical marker than WC or WHR when evaluating the role of obesity in the development of dementia and perhaps AD in particular.