@article{8eb4c5e7114c44fcaea27c4e8cef7281,
title = "Sex- and age-specific associations between cardiometabolic risk and white matter brain age in the UK Biobank cohort",
abstract = "Cardiometabolic risk (CMR) factors are associated with accelerated brain aging and increased risk for sex-dimorphic illnesses such as Alzheimer's disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E-epsilon 4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi-shell diffusion-weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied (i) between males and females, (ii) according to age at menopause in females, and (iii) across different age groups in males and females. We report sex differences in associations between BAG and all three CMRs, with stronger positive associations among males compared to females. Independent of APOE4 status, higher BAG (older brain age relative to chronological age) was associated with greater BMI, WHR, and BF% in males, whereas in females, higher BAG was associated with greater WHR, but not BMI and BF%. These divergent associations were most prominent within the oldest group of females (66-81 years), where greater BF% was linked to lower BAG. Earlier menopause transition was associated with higher BAG, but no interactions were found with CMRs. In conclusion, the findings point to sex- and age-specific associations between CMRs and brain age. Incorporating sex as a factor of interest in studies addressing CMR may promote sex-specific precision medicine, consequently improving health care for both males and females.",
keywords = "APOE genetic risk, brain age, cardiometabolic health, menopause, sex differences, BODY-MASS INDEX, APOLIPOPROTEIN-E GENOTYPE, CORONARY-HEART-DISEASE, COGNITIVE IMPAIRMENT, ALZHEIMERS-DISEASE, VISCERAL OBESITY, FAT PERCENTAGE, ADIPOSE-TISSUE, BLOOD-PRESSURE, FEMALE SEX",
author = "S. Subramaniapillai and S. Suri and C. Barth and I.I. Maximov and I. Voldsbekk and {Van der Meer}, D. and T.P. Gurholt and D. Beck and B. Draganski and O.A. Andreassen and K.P. Ebmeier and L.T. Westlye and {De Lange}, A.M.G.",
note = "Funding Information: This research has been conducted using the UK Biobank under Application 27412. UKB has received ethics approval from the National Health Service National Research Ethics Service (ref 11/NW/0382). The work was performed on the Service for Sensitive Data (TSD) platform, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo IT-Department (USIT). Computations were also performed using resources provided by UNINETT Sigma2—the National Infrastructure for High Performance Computing and Data Storage in Norway. While working on this study, the authors received funding from the Women in Cognitive Science-Canada (Sivaniya Subramaniapillai), NSERC Michael Smith Foreign Study Supplement (Sivaniya Subramaniapillai), Healthy Brains Healthy Lives (Sivaniya Subramaniapillai), the Alzheimer's Society (Sana Suri; 441), the Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award (Sana Suri; SBF006\1078), the Research Council of Norway (Lars T. Westlye; 273345, 249795, 298646, 300768, 223273; Ole A. Andreassen; 223273, 283799, 2837989), the South-Eastern Norway Regional Health Authority (Lars T. Westlye; 2018076, 2019101, Ole A. Andreassen; 2019-108, 2017-112, Tiril P. Gurholt; 2022080), the European Research Council under the European Union's Horizon 2020 research and innovation programme (Lars T. Westlye; 802998, Ole A. Andreassen; 847776, Klaus P. Ebmeier; 732592), the HDH Wills 1965 Charitable Trust (Klaus P. Ebmeier; 1117747), the Leenaards Foundation (Bogdan Draganski), and the Swiss National Science Foundation (Ann-Marie G. de Lange; PZ00P3_193658; Bogdan Draganski; NCCR Synapsy, project grants Nr 32003B_135679, 32003B_159780, 324730_192755, and CRSK-3_190185). The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z). Funding Information: Alzheimer's Society, Grant/Award Number: 441; Fondation Leenaards; H2020 European Research Council, Grant/Award Numbers: 732592, 802998, 847776; Healthy Brains Healthy Lives; Helse S{\o}r‐{\O}st RHF, Grant/Award Numbers: 2017‐112, 2018076, 2019‐108, 2019101, 2022080; Norges Forskningsr{\aa}d, Grant/Award Numbers: 223273, 249795, 273345, 2837989, 283799, 298646, 300768; NSERC Michael Smith Foreign Study Supplement; Schweizerischer Nationalfonds zur F{\"o}rderung der Wissenschaftlichen Forschung, Grant/Award Numbers: 32003B_135679, 32003B_159780, 324730_192755, CRSK‐ 3_190185, PZ00P3_193658; The Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award, Grant/Award Number: SBF006\1078; the HDH Wills 1965 Charitable Trust, Grant/Award Number: 1117747; Wellcome Trust, Grant/Award Number: 203139/Z/16/Z; Women in Cognitive Science‐Canada Funding information Funding Information: This research has been conducted using the UK Biobank under Application 27412. UKB has received ethics approval from the National Health Service National Research Ethics Service (ref 11/NW/0382). The work was performed on the Service for Sensitive Data (TSD) platform, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo IT‐Department (USIT). Computations were also performed using resources provided by UNINETT Sigma2—the National Infrastructure for High Performance Computing and Data Storage in Norway. While working on this study, the authors received funding from the Women in Cognitive Science‐Canada (Sivaniya Subramaniapillai), NSERC Michael Smith Foreign Study Supplement (Sivaniya Subramaniapillai), Healthy Brains Healthy Lives (Sivaniya Subramaniapillai), the Alzheimer's Society (Sana Suri; 441), the Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award (Sana Suri; SBF006\1078), the Research Council of Norway (Lars T. Westlye; 273345, 249795, 298646, 300768, 223273; Ole A. Andreassen; 223273, 283799, 2837989), the South‐Eastern Norway Regional Health Authority (Lars T. Westlye; 2018076, 2019101, Ole A. Andreassen; 2019‐108, 2017‐112, Tiril P. Gurholt; 2022080), the European Research Council under the European Union's Horizon 2020 research and innovation programme (Lars T. Westlye; 802998, Ole A. Andreassen; 847776, Klaus P. Ebmeier; 732592), the HDH Wills 1965 Charitable Trust (Klaus P. Ebmeier; 1117747), the Leenaards Foundation (Bogdan Draganski), and the Swiss National Science Foundation (Ann‐Marie G. de Lange; PZ00P3_193658; Bogdan Draganski; NCCR Synapsy, project grants Nr 32003B_135679, 32003B_159780, 324730_192755, and CRSK‐3_190185). The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z). Publisher Copyright: {\textcopyright} 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.",
year = "2022",
month = aug,
day = "15",
doi = "10.1002/hbm.25882",
language = "English",
volume = "43",
pages = "3759--3774",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley",
number = "12",
}