Authors
Miaomiao Zhu, Fan Yang, Jia Guo, Yifan Wang, Qian Wang, Qingyin Bu, Longhu Sun, Zhazheng He, Tianchen Qi, Junru Zhu, Gaoming Tang, Shuang Liang, Honggang Yi, Juncheng Dai
Published in
Obesity (Silver Spring, Md.). Sep 06, 2026. Epub Sep 06, 2026.
Abstract
This study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex-specific brain aging.
We analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females). Sex-specific XGBoost models estimated multimodal brain age. We derived 16-year longitudinal obesity trajectories from repeatedly collected anthropometric measurements. Polygenic risk scores were constructed based on 55 independent genetic loci. Multivariable logistic regression examined associations of obesity trajectories and genetic risk with brain age acceleration.
A total of 8198 (49.73%) males and 9089 (48.84%) females had accelerated brain aging. High genetic risk significantly increased brain age acceleration odds (males: OR = 1.39; females: OR = 1.34). Crucially, the high-stable obesity trajectory exerted a stronger effect in males (OR = 1.90, 95% CI: 1.64-2.21) than in females (OR = 1.25, 95% CI: 1.12-1.40), with the joint presence of high genetic risk and high-stable obesity amplifying risk to an OR of 2.78 in males and 1.57 in females. Conversely, shifting from obesity to non-obesity reduced risk by 30% in males and 18% in females.
These findings underscore long-term obesity as a critical, sex-dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.
PMID:
42702823
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.
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