Measures of Adiposity and Alzheimer's Disease-Related MRI Markers: The Northern Manhattan Study

Background: Adiposity may increase risk for dementia and Alzheimer's disease (AD), but mechanisms are unclear. Objective: To examine associations between measures of adiposity with AD-signature region cortical thickness and hippocampal volume. Methods: We used data from the Northern Manhattan Study, a clinically stroke-free cohort of mostly Hispanic participants. Exposures of interest included body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC), and adiponectin concentration, measured at study entry. AD-signature region cortical thickness and hippocampal volume were obtained using Freesurfer. We estimated associations using multivariable linear regression, adjusting for sociodemographics and health behaviors. We re-examined estimates after adjustment for APOE ϵ4 allele status or carotid intima-media thickness (cIMT), among those cognitively unimpaired, and after weighting for the inverse probability of selection into the MRI sub-study. We also repeated analyses for cortical thickness in non-AD signature regions. Results: The sample (N = 947, 63% women, 66% Hispanic/Latino, 26% obese) had a mean (SD) age = 63 (8) years. Greater BMI and WC (both z-scored) were associated with thinner AD-signature region cortex (also z-scored) (BMI: β [95% CI] = -0.09 [-0.18, -0.01], WC: β [95% CI] = -0.11 [-0.20, -0.02]). We did not find evidence that adiposity was related to hippocampal volume. Results were consistent after adjustment for APOE ϵ4 allele status or cIMT, after weighting for selection, among those cognitively unimpaired, and for non-AD signature region cortical thickness. Conclusion: Greater BMI and WC were related to cortical thinning within and outside the AD-signature region, suggesting a global effect not specific to AD.