Abdominal adiposity and Alzheimer's disease imaging markers across sex and race at midlife

Background: Midlife obesity is considered one of the top modifiable risk factors for dementia and Alzheimer's disease (AD). However, body mass index (BMI) on its own does not fully represent obesity-associated risks and it is crucial to disentangle the role of body adiposity and its localization. Objective: To investigate the relationship of MRI-derived body adiposity metrics with AD-related pathology at midlife. Methods: Ninety-seven cognitively normal midlife individuals underwent brain amyloid and tau PET, body MRI, and metabolic and cognitive assessments. Key measures included hepatic fat fraction, visceral (VAT) and subcutaneous adipose tissue (SAT) volumes, and thigh muscle and adiposity. The correlation between adiposity/metabolic measurements and amyloid/tau pathologies was investigated. Results: The average age of participants was 49.8 years, 65.3% were female and 53.6% had obesity. Amyloid PET burden in Centiloids correlated with VAT (rho = 0.36, p = 0.002), BMI (rho = 0.33, p = 0.002), SAT (rho = 0.33, p = 0.002), and insulin resistance (IR) (rho = 0.34, p = 0.003) in females and Whites, lower high-density lipoprotein (HDL) cholesterol (rho = −0.36, p = 0.002) irrespective of sex and race, and lower MMSE scores (rho = −0.57, p = 0.043) in only in African-Americans, after correction for age, sex, and education. There was no evidence that HDL nor IR mediated VAT-related amyloid. VAT/SAT ratio was significantly associated with mean cortical tau SUVR (β = 0.138, p = 0.030) after adjustment for age, sex, education, and amyloid. Conclusions: Among fat depots in our study, visceral fat was more strongly correlated to amyloid pathology, and this association is present even independent from BMI. Also, higher visceral compared to subcutaneous fat is related to higher tau pathology.