Abdominal Fat Depots are Related to Lower Cognitive Functioning and Brain Volumes in Middle‐aged Males at High Alzheimer’s Risk

Abstract Background High body mass index (BMI), which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. We examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association. Method 204 healthy middle‐aged Alzheimer’s‐dementia (AD) offspring (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral (VAT), and subcutaneous adipose tissue (SAT), assessment of cognition and brain volumes. Result In the whole sample higher hepatic fat % was associated with lower total grey matter volume (β = ‐0.17, p<0.01). Primarily in males, higher pancreatic fat % was associated with lower global cognition (Males: β = ‐0.27, p = 0.03; Females: β = 0.01, p = 0.93) executive function (Males: β = ‐0.27, p = 0.03; Females: β = 0.02, p = 0.87), episodic memory (Males: β = ‐0.28, p = 0.03; Females: β = 0.07, p = 0.48) and inferior frontal gyrus volume (Males: β = ‐0.28, p = 0.02; Females: β = 0.10, p = 0.33). VAT and SAT were inversely associated with middle frontal and superior frontal gyrus volumes in males and females. Conclusion In middle‐aged males at high AD‐risk, but not in females, higher pancreatic fat, was associated with lower cognition and brain volumes. These findings suggest a potential sex‐specific link between distinct abdominal fat with brain health. By AAIC 2024 300 participants will be scanned, additional brain pathlogies will be assesed (amyloid, tau, etc.) and secreted factors will be evaluated (GLP‐1, Amylin, PAI‐1, leptin, etc). These data may lead to the development of fat depot‐specific interventions, which are expected to prevent or delay brain atrophy and possibly cognitive decline.