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Network analysis provides a novel approach to examine these relationships, offering insights into sex\u2010specific risk factor connectivity in healthy controls (HCs) and individuals with mild cognitive impairment or Alzheimer's disease (cognitive decline [CD]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A network analysis of 896 participants examined associations among modifiable, non\u2010modifiable, and cognitive risk factors. Network invariance and global strength tests assessed structural and connectivity differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In males, network invariance differed between HC and CD groups, but connectivity was unchanged. In females, network invariance and connectivity were significantly altered, with HC females exhibiting stronger overall connectivity. Key risk factors in females included systolic blood pressure and apolipoprotein E \u03b54, whereas males\u2019 networks were primarily influenced by cognitive outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Sex\u2010specific networks suggest distinct mechanisms underlying cognitive decline. Future work differentiating mild cognitive impairment and Alzheimer's disease stages will refine our understanding of risk factor evolution and inform precision medicine approaches to dementia prevention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Sex\u2010stratified networks of risk factors differ in healthy and cognitively impaired adults.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Female networks show greater global connectivity in healthy versus cognitively decline groups.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Apolipoprotein E, family history, and lifestyle factors show sex\u2010specific centrality in networks.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Network structure changes more in females across the cognitive decline spectrum.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Findings support sex\u2010specific modeling of dementia risk for precision prevention.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70825","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T10:34:31Z","timestamp":1763807671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring sex\u2010specific risk factors in cognitive decline: Insights into modifiable and non\u2010modifiable determinants using a network analysis"],"prefix":"10.1002","volume":"21","author":[{"given":"Brittany","family":"Intzandt","sequence":"first","affiliation":[{"name":"School of Kinesiology and Health Science Centre for Integrative and Applied Neuroscience York University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Ramirez","sequence":"additional","affiliation":[{"name":"The Dr. Sandra Black Centre for Brain Resilience and Recovery Cognitive Neurology Research Unit Hurvitz Brain Sciences Sunnybrook Research Institute University of Toronto  Toronto Ontario Canada"},{"name":"Graduate Department of Psychological Clinical Sciences University of Toronto Scarborough  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Lam","sequence":"additional","affiliation":[{"name":"The Dr. Sandra Black Centre for Brain Resilience and Recovery Cognitive 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