{"title":"tau病理易感性的性别差异：对认知能力下降的影响","authors":"Yashar Zeighami, Cecilia Tremblay, Mahsa Dadar","doi":"10.1002/alz.70634","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Although the link between the presence of amyloid and tau pathologies, neurodegeneration, and cognitive decline in aging individuals is established, it is less clear whether there are sex differences in vulnerability to these pathologies.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>A total of 1464 participants (7168 longitudinal assessments, 4.77 ± 3.78 years of follow-up) were included from the National Alzheimer's Coordinating Center (NACC) database. Longitudinal mixed effects and mediation models examined the sex differences across cognitive decline trajectories of amyloid (A), tau (T), and neurodegeneration (N) groups.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>A<sup>+</sup>T<sup>−</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>−</sup> females (<i>p</i> < 0.005), whereas A<sup>+</sup>T<sup>+</sup> females showed steeper cognitive decline compared to A<sup>+</sup>T<sup>+</sup> males (<i>p</i> < 0.0001). In addition, sex marginally moderated the mediating effect of tau on the relationship between amyloid and cognitive decline (<i>p</i> = 0.046).</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Sex differences in vulnerability to tau pathology in the presence of amyloid can shape cognitive decline trajectories.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>A<sup>+</sup>T<sup>−</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>−</sup> females.</li>\n \n <li>A<sup>+</sup>T<sup>+</sup> females showed faster cognitive decline compared to A<sup>+</sup>T<sup>+</sup> males.</li>\n \n <li>Tau status significantly mediated the relationship between amyloid status and cognitive decline.</li>\n \n <li>Sex marginally moderated the mediating relationship between amyloid, tau, and cognitive decline.</li>\n \n <li>The findings point to sex differences in the impact of tau pathology on cognition.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70634","citationCount":"0","resultStr":"{\"title\":\"Sex differences in vulnerability to tau pathology: Impact on cognitive decline\",\"authors\":\"Yashar Zeighami, Cecilia Tremblay, Mahsa Dadar\",\"doi\":\"10.1002/alz.70634\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>Although the link between the presence of amyloid and tau pathologies, neurodegeneration, and cognitive decline in aging individuals is established, it is less clear whether there are sex differences in vulnerability to these pathologies.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>A total of 1464 participants (7168 longitudinal assessments, 4.77 ± 3.78 years of follow-up) were included from the National Alzheimer's Coordinating Center (NACC) database. Longitudinal mixed effects and mediation models examined the sex differences across cognitive decline trajectories of amyloid (A), tau (T), and neurodegeneration (N) groups.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>A<sup>+</sup>T<sup>−</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>−</sup> females (<i>p</i> < 0.005), whereas A<sup>+</sup>T<sup>+</sup> females showed steeper cognitive decline compared to A<sup>+</sup>T<sup>+</sup> males (<i>p</i> < 0.0001). In addition, sex marginally moderated the mediating effect of tau on the relationship between amyloid and cognitive decline (<i>p</i> = 0.046).</p>\\n </section>\\n \\n <section>\\n \\n <h3> DISCUSSION</h3>\\n \\n <p>Sex differences in vulnerability to tau pathology in the presence of amyloid can shape cognitive decline trajectories.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>A<sup>+</sup>T<sup>−</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>−</sup> females.</li>\\n \\n <li>A<sup>+</sup>T<sup>+</sup> females showed faster cognitive decline compared to A<sup>+</sup>T<sup>+</sup> males.</li>\\n \\n <li>Tau status significantly mediated the relationship between amyloid status and cognitive decline.</li>\\n \\n <li>Sex marginally moderated the mediating relationship between amyloid, tau, and cognitive decline.</li>\\n \\n <li>The findings point to sex differences in the impact of tau pathology on cognition.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":7471,\"journal\":{\"name\":\"Alzheimer's & Dementia\",\"volume\":\"21 10\",\"pages\":\"\"},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2025-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70634\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer's & Dementia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70634\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70634","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Sex differences in vulnerability to tau pathology: Impact on cognitive decline
INTRODUCTION
Although the link between the presence of amyloid and tau pathologies, neurodegeneration, and cognitive decline in aging individuals is established, it is less clear whether there are sex differences in vulnerability to these pathologies.
METHODS
A total of 1464 participants (7168 longitudinal assessments, 4.77 ± 3.78 years of follow-up) were included from the National Alzheimer's Coordinating Center (NACC) database. Longitudinal mixed effects and mediation models examined the sex differences across cognitive decline trajectories of amyloid (A), tau (T), and neurodegeneration (N) groups.
RESULTS
A+T− males showed faster cognitive decline compared to A+T− females (p < 0.005), whereas A+T+ females showed steeper cognitive decline compared to A+T+ males (p < 0.0001). In addition, sex marginally moderated the mediating effect of tau on the relationship between amyloid and cognitive decline (p = 0.046).
DISCUSSION
Sex differences in vulnerability to tau pathology in the presence of amyloid can shape cognitive decline trajectories.
Highlights
A+T− males showed faster cognitive decline compared to A+T− females.
A+T+ females showed faster cognitive decline compared to A+T+ males.
Tau status significantly mediated the relationship between amyloid status and cognitive decline.
Sex marginally moderated the mediating relationship between amyloid, tau, and cognitive decline.
The findings point to sex differences in the impact of tau pathology on cognition.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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