Differential sex associations of regional adiposity with cognition and brain pathology in Israeli older adults with Type II Diabetes

Abstract

AbstractBackgroundAdiposity and Type II diabetes (T2D) are consistently associated with cognitive impairment and dementia. Body mass index (BMI) is the most common measure of global adiposity, but its associations with cognition in old age are inconsistent. BMI does not represent regional fat distribution, which might differ between the sexes. In this study, we examined sex differences in the relationships of regional adiposity with cognition and AD‐related brain volumes in older adults participating in the Israel Diabetes and Cognitive Decline study.MethodsRegional adiposity was measured by abdominal MRI in 89 participants (32.6% women), including hepatic and pancreatic fat, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Participants were assessed for global cognition, episodic memory (EP), working memory (WM), executive function (EF), and language. A subsample (N = 50) underwent brain MRI assessing total gray matter [GM], hippocampus, inferior, middle, and superior frontal gyrus [IFG, MFG, and SFG, respectively]. Linear regressions examined associations of regional adiposity with cognition and AD‐related brain volumes adjusting for age, sex, education, and BMI (and intracranial volume for MRI measures).ResultsIn the whole sample, higher pancreatic fat was associated with lower EF (r = ‐0.369, p = 0.024). In men, high pancreatic fat was associated with lower global cognition (Men: r = ‐0.311; p = 0.048; Women: r = ‐0.122; p = 0.706), EF (Men: r = ‐0.384; p = 0.033; Women: r = ‐0.508; p = 0.661) and language (Men: r = ‐0.309; p = 0.049; Women: r = 0.082; p = 0.798). In the whole sample, no associations were found between pancreatic fat % and AD‐related brain volumes. Surprisingly, in men, higher pancreatic fat was associated with greater GM volume (Men: r = 0.411; p = 0.046; Women: r = ‐0.231; p = 0.521). In women, higher pancreatic fat was associated with smaller IFG (Men: r = ‐0.185, p = 0.386; Women: r = ‐0.642, p = 0.045). Hepatic fat %, VAT, and SAT did not associate with AD‐related brain volumes or cognitive measures.ConclusionIn Israeli older adults with T2D, different regional fat depots are linked to different cognitive and brain outcomes in men and women. Specifically, more pancreatic fat, but not other fat depots, is associated with poorer cognition. These findings highlight the value of examining distinct fat depots rather than global obesity concerning brain and cognition, and the need to account for sex differences in these associations.