Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank

Objective: To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Methods: Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyper-intensities (WMH), and fluid intelligence score (FIS) were estimated in 30283...

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Main Authors: Panlong Li, Xirui Zhu, Chun Huang, Shan Tian, Yuna Li, Yuan Qiao, Min Liu, Jingjing Su, Dandan Tian
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:IBRO Neuroscience Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667242125000016
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author Panlong Li
Xirui Zhu
Chun Huang
Shan Tian
Yuna Li
Yuan Qiao
Min Liu
Jingjing Su
Dandan Tian
author_facet Panlong Li
Xirui Zhu
Chun Huang
Shan Tian
Yuna Li
Yuan Qiao
Min Liu
Jingjing Su
Dandan Tian
author_sort Panlong Li
collection DOAJ
description Objective: To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Methods: Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyper-intensities (WMH), and fluid intelligence score (FIS) were estimated in 30283 participants from the UK Biobank. Longitudinal data analysis was conducted. Genome-wide association studies were applied to explore the genetic loci associations among BMI, GMV, WMH, and FIS. Mendelian Randomization analyses were applied to further estimate the effects of obesity on changes in the brain and cognition. Results: The observational analysis revealed that BMI was negatively associated with GMV (r = -0.15, p < 1×10−24) and positively associated with WMH (r = 0.08, p < 1×10−16). The change in BMI was negatively associated with the change in GMV (r = -0.04, p < 5×10−5). Genetic overlap was observed among BMI, GMV, and FIS at SBK1 (rs2726032), SGF29 (rs17707300), TUFM (rs3088215), AKAP6 (rs1051695), IL27 (rs4788084), and SPI1 (rs3740689 and rs935914). The MR analysis provided evidence that higher BMI was associated with lower GMV (β=-1119.12, p = 5.77 ×10−6), higher WMH (β=42.76, p = 6.37 ×10−4), and lower FIS (β=-0.081, p = 1.92 ×10−23). Conclusions: The phenotypic and genetic association between obesity and aging brain and cognitive decline suggested that weight control could be a promising strategy for slowing the aging brain.
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spelling doaj-art-dcb7913c755c43f9a85ebe087e0193a02025-08-20T03:20:58ZengElsevierIBRO Neuroscience Reports2667-24212025-06-011814815710.1016/j.ibneur.2025.01.001Effects of obesity on aging brain and cognitive decline: A cohort study from the UK BiobankPanlong Li0Xirui Zhu1Chun Huang2Shan Tian3Yuna Li4Yuan Qiao5Min Liu6Jingjing Su7Dandan Tian8School of Electrical and Information Engineering, Zhengzhou University of Light Industry, Zhengzhou, ChinaSchool of Electrical and Information Engineering, Zhengzhou University of Light Industry, Zhengzhou, ChinaSchool of Electrical and Information Engineering, Zhengzhou University of Light Industry, Zhengzhou, ChinaDepartment of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Hypertension, Henan Provincial People’s Hospital &amp; Zhengzhou University People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authors.Department of Hypertension, Henan Provincial People’s Hospital &amp; Zhengzhou University People’s Hospital, Zhengzhou, China; Corresponding authors.Objective: To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Methods: Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyper-intensities (WMH), and fluid intelligence score (FIS) were estimated in 30283 participants from the UK Biobank. Longitudinal data analysis was conducted. Genome-wide association studies were applied to explore the genetic loci associations among BMI, GMV, WMH, and FIS. Mendelian Randomization analyses were applied to further estimate the effects of obesity on changes in the brain and cognition. Results: The observational analysis revealed that BMI was negatively associated with GMV (r = -0.15, p < 1×10−24) and positively associated with WMH (r = 0.08, p < 1×10−16). The change in BMI was negatively associated with the change in GMV (r = -0.04, p < 5×10−5). Genetic overlap was observed among BMI, GMV, and FIS at SBK1 (rs2726032), SGF29 (rs17707300), TUFM (rs3088215), AKAP6 (rs1051695), IL27 (rs4788084), and SPI1 (rs3740689 and rs935914). The MR analysis provided evidence that higher BMI was associated with lower GMV (β=-1119.12, p = 5.77 ×10−6), higher WMH (β=42.76, p = 6.37 ×10−4), and lower FIS (β=-0.081, p = 1.92 ×10−23). Conclusions: The phenotypic and genetic association between obesity and aging brain and cognitive decline suggested that weight control could be a promising strategy for slowing the aging brain.http://www.sciencedirect.com/science/article/pii/S2667242125000016ObesityGray matter atrophyWhite matter hyper-intensitiesGenetic overlapMendelian randomization
spellingShingle Panlong Li
Xirui Zhu
Chun Huang
Shan Tian
Yuna Li
Yuan Qiao
Min Liu
Jingjing Su
Dandan Tian
Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank
IBRO Neuroscience Reports
Obesity
Gray matter atrophy
White matter hyper-intensities
Genetic overlap
Mendelian randomization
title Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank
title_full Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank
title_fullStr Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank
title_full_unstemmed Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank
title_short Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank
title_sort effects of obesity on aging brain and cognitive decline a cohort study from the uk biobank
topic Obesity
Gray matter atrophy
White matter hyper-intensities
Genetic overlap
Mendelian randomization
url http://www.sciencedirect.com/science/article/pii/S2667242125000016
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