Abstract

Introduction: Mid-life and late-life obesity have been associated with changes in brain structure and function, though the exact nature of this dynamic relationship is not well understood. Purpose: To determine whether associations between measures of obesity and neuroimaging biomarkers are independent of cardiometabolic health status in older adults. Methods: Adults 55 and older were recruited into the Clinical Core of the Wake Forest Alzheimer’s Disease Research Center (ADRC) between 2016 and 2023 and underwent standard evaluation in accordance with the National Alzheimer’s Coordinating Center protocols. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) were measured to assess obesity. Cardiometabolic health was determined by the presence of impaired glucose tolerance (IGT) and hypertension (HTN). Brain MRI scans were conducted to assess cerebral blood flow (CBF) in white matter (WM) and gray matter (GM), WM microstructure using neurite orientation dispersion and density imaging (NODDI) of free water (FW), total brain volume (GM+WM), and temporal lobe cortical thickness. Linear regression was used to examine associations between anthropometric and neuroimaging measures, controlling for demographics (age, gender, race, education) in model 1 and demographics plus cardiometabolic health (HTN and IGT) in model 2. Results: A total of 647 Clinical Core participants with anthropometric, MRI, cardiometabolic, and demographic data available were analyzed. Mean age of participants was 70.1±8.2 years, 19% were African American, 48% had adjudicated cognitive impairment (35% mild cognitive impairment, 13% dementia), 76% had HTN, and 69% had IGT. BMI (p<0.001), WC (p<0.001), and WHR (p=0.006) were positively associated with WM CBF in models 1 and 2. BMI (p=0.039) was also positively associated with GM CBF in model 2. All three obesity measures were positively associated with NODDI FW in model 1: BMI (p=0.006), WC (p=0.007), and WHR (p=0.039), and WHR was negatively associated with total brain volume (p=0.043). However, these associations were attenuated after further adjustment. Cortical thickness was not significantly associated with obesity in any model. Conclusion: These results demonstrate that, among community-dwelling older adults, having higher BMI, WHR, and WC is associated with higher WM CBF even after adjusting for demographics, HTN and IGT, suggesting that obesity may be a risk factor for impaired brain perfusion in late life.

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