Abdominal fat depots are related to lower cognitive functioning and brain volumes in middle-aged males at high Alzheimer's risk

Sapir Golan Shekhtman, Ethel Boccara, Ramit Ravona-Springer, Yael Inbar, Hila Zelicha, Abigail Livny, Barbara B. Bendlin, Orit Lesman-Segev, Iscka Yore, Anthony Heymann, Mary Sano, Yael Mardor, Joseph Azuri, Michal Schnaider Beeri

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Objective: High BMI, which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. This study examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association. Methods: A total of 204 healthy middle-aged offspring of Alzheimer's dementia patients (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral, and subcutaneous adipose tissue and to assess cognition and brain volumes. Results: In the whole sample, higher hepatic fat percentage was associated with lower total gray matter volume (β = −0.17, p < 0.01). Primarily in males, higher pancreatic fat percentage 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). Visceral and subcutaneous adipose tissue was inversely associated with middle frontal and superior frontal gyrus volumes in males and females. Conclusions: In middle-aged males at high Alzheimer's dementia 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.

Original languageEnglish
Pages (from-to)1009-1022
Number of pages14
Issue number5
Early online date27 Feb 2024
StatePublished - May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.


This work was supported by NIH grants R01AG034087, AG053446, AG051545, and AG043878 to Dr. Beeri, P50 AG05138 to Dr. Sano, and AACSF‐21‐850735 to Dr. Lesman‐Segev. We are also grateful for the generosity of the Katzin Foundation, the LeRoy Schecter Foundation, and Dr. Marina Nissim and for scholarships from The Herczeg Institute on Agin, The Prajs‐Drimmer Institute for Development of Anti‐Degenerative Drugs, and Tel Aviv University Healthy Longevity Research Center.

FundersFunder number
National Institutes of HealthAG051545, R01AG034087, AG043878, P50 AG05138, AACSF‐21‐850735, AG053446


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