Tatiana Dessy, Amina Barhdadi, Marie-Christyne Cyr, Johanna Sandoval, Louis Bherer, Joëlle Rouleau, Sylvie Provost, Louis-Philippe Lemieux Perreault, Marie-Pierre Sylvestre, Sarah A Gagliano Taliun, Marie-Pierre Dubé
{"title":"性别对apoe4相关神经认知障碍的影响。","authors":"Tatiana Dessy, Amina Barhdadi, Marie-Christyne Cyr, Johanna Sandoval, Louis Bherer, Joëlle Rouleau, Sylvie Provost, Louis-Philippe Lemieux Perreault, Marie-Pierre Sylvestre, Sarah A Gagliano Taliun, Marie-Pierre Dubé","doi":"10.1002/dad2.70111","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The apolipoprotein E (<i>APOE</i>) ɛ4 allele is a well-established risk factor for neurocognitive impairment (NCI), with varying impacts between men and women. This study investigates the distinct roles of sex and gender in modifying <i>APOE</i> ɛ4-related NCI.</p><p><strong>Methods: </strong>Biological sex was inferred from sex chromosomes, and a femininity score (FS) was used as a proxy for gender. We analyzed 276,596 UK Biobank participants without prior NCI to assess whether sex and FS modified the effect of <i>APOE</i> ɛ4 on NCI.</p><p><strong>Results: </strong>NCI risk was higher in <i>APOE</i> ɛ4 carriers compared to non-carriers (hazard ratio [HR] = 2.48 in females; HR = 1.96 in males) with significant interaction by sex (<i>P</i> < 0.0001). FS was associated with an increased NCI risk after accounting for sex (HR = 1.07, 95% confidence interval: 1.04-1.10, <i>P</i> < 0.0001) with no significant differences by sex or <i>APOE</i> ɛ4 carrier status.</p><p><strong>Discussion: </strong>Our findings show that <i>APOE</i> ɛ4 increases NCI risk more in females, while FS independently elevates risk across sexes.</p><p><strong>Highlights: </strong>Apolipoprotein E (<i>APOE</i>) ɛ4 increases neurocognitive impairment (NCI) risk, with a greater impact in females (hazard ratio [HR] = 2.48) than males (HR = 1.96).Sex significantly modifies the effect of <i>APOE</i> ɛ4 on NCI (<i>P</i> < 0.0001f).Femininity score increases NCI risk (HR = 1.07) independently of sex and <i>APOE</i> ɛ4.Understanding the distinct sex and gender contributions to <i>APOE</i> ɛ4-related NCI can improve interventions.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70111"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064333/pdf/","citationCount":"0","resultStr":"{\"title\":\"Disentangling the effects of sex and gender on <i>APOE</i> ɛ4-related neurocognitive impairment.\",\"authors\":\"Tatiana Dessy, Amina Barhdadi, Marie-Christyne Cyr, Johanna Sandoval, Louis Bherer, Joëlle Rouleau, Sylvie Provost, Louis-Philippe Lemieux Perreault, Marie-Pierre Sylvestre, Sarah A Gagliano Taliun, Marie-Pierre Dubé\",\"doi\":\"10.1002/dad2.70111\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The apolipoprotein E (<i>APOE</i>) ɛ4 allele is a well-established risk factor for neurocognitive impairment (NCI), with varying impacts between men and women. This study investigates the distinct roles of sex and gender in modifying <i>APOE</i> ɛ4-related NCI.</p><p><strong>Methods: </strong>Biological sex was inferred from sex chromosomes, and a femininity score (FS) was used as a proxy for gender. We analyzed 276,596 UK Biobank participants without prior NCI to assess whether sex and FS modified the effect of <i>APOE</i> ɛ4 on NCI.</p><p><strong>Results: </strong>NCI risk was higher in <i>APOE</i> ɛ4 carriers compared to non-carriers (hazard ratio [HR] = 2.48 in females; HR = 1.96 in males) with significant interaction by sex (<i>P</i> < 0.0001). FS was associated with an increased NCI risk after accounting for sex (HR = 1.07, 95% confidence interval: 1.04-1.10, <i>P</i> < 0.0001) with no significant differences by sex or <i>APOE</i> ɛ4 carrier status.</p><p><strong>Discussion: </strong>Our findings show that <i>APOE</i> ɛ4 increases NCI risk more in females, while FS independently elevates risk across sexes.</p><p><strong>Highlights: </strong>Apolipoprotein E (<i>APOE</i>) ɛ4 increases neurocognitive impairment (NCI) risk, with a greater impact in females (hazard ratio [HR] = 2.48) than males (HR = 1.96).Sex significantly modifies the effect of <i>APOE</i> ɛ4 on NCI (<i>P</i> < 0.0001f).Femininity score increases NCI risk (HR = 1.07) independently of sex and <i>APOE</i> ɛ4.Understanding the distinct sex and gender contributions to <i>APOE</i> ɛ4-related NCI can improve interventions.</p>\",\"PeriodicalId\":53226,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"volume\":\"17 2\",\"pages\":\"e70111\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064333/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/dad2.70111\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70111","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Disentangling the effects of sex and gender on APOE ɛ4-related neurocognitive impairment.
Introduction: The apolipoprotein E (APOE) ɛ4 allele is a well-established risk factor for neurocognitive impairment (NCI), with varying impacts between men and women. This study investigates the distinct roles of sex and gender in modifying APOE ɛ4-related NCI.
Methods: Biological sex was inferred from sex chromosomes, and a femininity score (FS) was used as a proxy for gender. We analyzed 276,596 UK Biobank participants without prior NCI to assess whether sex and FS modified the effect of APOE ɛ4 on NCI.
Results: NCI risk was higher in APOE ɛ4 carriers compared to non-carriers (hazard ratio [HR] = 2.48 in females; HR = 1.96 in males) with significant interaction by sex (P < 0.0001). FS was associated with an increased NCI risk after accounting for sex (HR = 1.07, 95% confidence interval: 1.04-1.10, P < 0.0001) with no significant differences by sex or APOE ɛ4 carrier status.
Discussion: Our findings show that APOE ɛ4 increases NCI risk more in females, while FS independently elevates risk across sexes.
Highlights: Apolipoprotein E (APOE) ɛ4 increases neurocognitive impairment (NCI) risk, with a greater impact in females (hazard ratio [HR] = 2.48) than males (HR = 1.96).Sex significantly modifies the effect of APOE ɛ4 on NCI (P < 0.0001f).Femininity score increases NCI risk (HR = 1.07) independently of sex and APOE ɛ4.Understanding the distinct sex and gender contributions to APOE ɛ4-related NCI can improve interventions.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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