{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:34:20Z","timestamp":1793208860211,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82192904"],"award-info":[{"award-number":["82192904"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82192903"],"award-info":[{"award-number":["82192903"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex\u2010specific brain aging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females). Sex\u2010specific XGBoost models estimated multimodal brain age. We derived 16\u2010year 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2009=\u20091.39; females: OR\u2009=\u20091.34). Crucially, the high\u2010stable obesity trajectory exerted a stronger effect in males (OR\u2009=\u20091.90, 95% CI: 1.64\u20132.21) than in females (OR\u2009=\u20091.25, 95% CI: 1.12\u20131.40), with the joint presence of high genetic risk and high\u2010stable obesity amplifying risk to an OR of 2.78 in males and 1.57 in females. Conversely, shifting from obesity to non\u2010obesity reduced risk by 30% in males and 18% in females.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings underscore long\u2010term obesity as a critical, sex\u2010dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/oby.70304","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T04:27:31Z","timestamp":1788755251000},"page":"2135-2145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Joint Effects of Long\u2010Term Obesity and Genetic Susceptibility on Sex\u2010Specific Brain Aging"],"prefix":"10.1002","volume":"34","author":[{"given":"Miaomiao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyin","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhazheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianchen","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junru","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoming","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honggang","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juncheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"},{"name":"State Key Lab of Cancer Biomarkers, Prevention and Treatment; Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical University  Nanjing Jiangsu China"},{"name":"China International Cooperation Center for Environment and Human Health, Genomic Science and Precision Medicine Institute, Gusu School Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Life and Health Industry Academician Collaborative Innovation Center  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.931536"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.2010.21.3.187"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbas.2022.100032"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.10.001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00789"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-025-01100-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30367-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12071942"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20870"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibneur.2025.01.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.24309"},{"issue":"4","key":"e_1_2_10_13_1","first-page":"1831","article-title":"Visceral and Subcutaneous Abdominal Fat Predict Brain Volume Loss at Midlife in 10,001 Individuals","volume":"15","author":"Raji C. 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