{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T07:29:28Z","timestamp":1781594968799,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospital Samaritano Society","award":["25000.180.664\/2011-35"],"award-info":[{"award-number":["25000.180.664\/2011-35"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Metabolic syndrome (MetS) is linked to brain degeneration and Alzheimer\u2019s disease (AD). Women, especially during menopausal transition, show increased susceptibility to AD-related brain changes. This study investigated the sex-specific neurostructural impact of MetS on brain regions vulnerable to AD. Methods: This cross-sectional study analyzed data from 500 participants (303 women, 197 men) from the Baependi Heart Study cohort, Brazil. High-resolution T1-weighted MRI scans were used for volumetric analysis of AD-related regions of interest (ROIs). Non-parametric quantile regression models compared ROI volumes between MetS and Non-MetS groups, stratified by sex and age (median split), adjusting for age and education. Results: No significant differences in ROI volume were observed between the MetS and Non-MetS groups in men. In women, findings were age-dependent. The younger cohort (\u226448 years) with MetS exhibited significantly smaller left hippocampal volume (p = 0.02) and a trend toward smaller left middle temporal gyrus volume (p = 0.05) compared to Non-MetS. The older cohort (&gt;48 years) with MetS showed a significantly larger right amygdala volume (p &lt; 0.001). Furthermore, age-related volume decline in the hippocampus and middle temporal gyrus was significant in Non-MetS women but not in women with MetS, suggesting that MetS may be a confounding factor in age-related neurodegeneration. Conclusions: MetS is associated with sex-specific alterations in AD-vulnerable brain structures. In women, MetS may influence medial temporal lobe atrophy pre-menopause, and is linked to amygdala enlargement post-menopause. These exploratory results generate the hypothesis that MetS may uniquely predispose women to AD-related neurodegeneration, which requires critical longitudinal confirmation.<\/jats:p>","DOI":"10.3390\/brainsci15121341","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T10:41:23Z","timestamp":1765968083000},"page":"1341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex-Specific Impact of Metabolic Syndrome on Brain Structures Vulnerable to Alzheimer\u2019s Disease: A Cross-Sectional Study in a Brazilian Cohort"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-9289","authenticated-orcid":false,"given":"Rodrigo","family":"Hohl","sequence":"first","affiliation":[{"name":"Department of Biophysics and Physiology, Institute of Biological Sciences, Federal University of Juiz de Fora (UFJF), Campus Universit\u00e1rio, Rua Jos\u00e9 Louren\u00e7o Kelmer, s\/n\u2014S\u00e3o Pedro, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Gabriele Fernandes","family":"de Morais","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Physiology, Institute of Biological Sciences, Federal University of Juiz de Fora (UFJF), Campus Universit\u00e1rio, Rua Jos\u00e9 Louren\u00e7o Kelmer, s\/n\u2014S\u00e3o Pedro, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8783-4013","authenticated-orcid":false,"given":"T\u00e2mara Pessanha","family":"Taporoski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Brooking","family":"Negr\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Instituto do Cora\u00e7\u00e3o (Heart Institute), University of S\u00e3o Paulo, S\u00e3o Paulo 05508-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7875-9445","authenticated-orcid":false,"given":"Simon L.","family":"Evans","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7YH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Maciel","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Instituto do Cora\u00e7\u00e3o (Heart Institute), University of S\u00e3o Paulo, S\u00e3o Paulo 05508-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre da Costa","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Instituto do Cora\u00e7\u00e3o (Heart Institute), University of S\u00e3o Paulo, S\u00e3o Paulo 05508-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael de Oliveira","family":"Alvim","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Federal University of Amazonas (UFAM), Manaus 69067-005, AM, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1590\/1413-812320202511.31202020","article-title":"Prevalence of the metabolic syndrome and its components in the Brazilian adult population","volume":"25","author":"Oliveira","year":"2020","journal-title":"Cienc. 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