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This study aimed to assess its sex\u2010 and age\u2010specific associations with Alzheimer\u2019s disease (AD) pathology using multimodal biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In two longitudinal cohorts (Hubei Memory and Aging Cohort Study [HMACS],\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a02,349; Alzheimer\u2019s Disease Neuroimaging Initiative [ADNI],\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01,858), we assessed body fat via Cl\u00ednica Universidad de Navarra\u2010Body Adiposity Estimator (CUN\u2010BAE) and performed sex\u2010\/age\u2010stratified analyses using multimodal biomarkers (plasma, cerebrospinal fluid [CSF], Positron Emission Computed Tomography [PET]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In adults \u226565 years of age, higher baseline and increasing CUN\u2010BAE were associated with lower risk of AD\u2010related mild cognitive impairment (MCI) and dementia, with stratified analyses suggesting distinct patterns by sex and age; however, formal interaction tests were non\u2010significant. Each 1% increase in \u0394CUN\u2010BAE at ages 70\u201374 was associated with lower normal cognition (NC)\u2010to\u2010MCI transition risk by 20%. In females, higher CUN\u2010BAE associated with lower phosphorylated tau 217 (p\u2010tau217) and nonlinearly with amyloid beta (A\u03b2)42 with an inflection point near 37.6%. In males, increasing adiposity correlated with lower p\u2010tau217 and neurofilament light chain (NfL). Neuroimaging revealed inverse associations with A\u03b2 deposition in females and with tau deposition in A\u03b2\u2010positive males with MCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Higher adiposity was associated with lower incidence of AD\u2010related decline and less pronounced pathology; stratified exploratory analyses suggested patterns by age and sex, although formal interaction tests were non\u2010significant. However, these observational findings do not support recommendations of blindly increasing body fat for dementia prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71848","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:30:35Z","timestamp":1790242235000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping sex\u2010specific associations of adiposity with age\u2010related cognitive decline and multimodal Alzheimer's pathology"],"prefix":"10.1002","volume":"22","author":[{"given":"Jingjing","family":"Zhang","sequence":"first","affiliation":[{"name":"Hubei Provincial Clinical Research Center for Alzheimer\u2019s Disease Tianyou Hospital Affiliated to Wuhan University of Science and Technology Wuhan University of Science and Technology  Wuhan China"},{"name":"Geriatric Hospital Affiliated to Wuhan University of Science and Technology Wuhan University of Science and Technology  Wuhan China"},{"name":"Brain Science and Advanced Technology Institute Wuhan University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Provincial Clinical Research Center for Alzheimer\u2019s Disease Tianyou Hospital Affiliated to Wuhan University of Science and Technology Wuhan University of Science and Technology  Wuhan China"},{"name":"Geriatric Hospital Affiliated to Wuhan University of Science and Technology Wuhan University of Science and Technology  Wuhan China"},{"name":"Brain Science and Advanced Technology Institute Wuhan University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueran","family":"Yang","sequence":"additional","affiliation":[{"name":"Faculty of Business and Management Beijing Normal\u2010Hong Kong Baptist University  Zhuhai 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