Madeline Wood Alexander, D Luke Fischer, Lawren VandeVrede, Emma Nichols, Lei Yu, James R Pike, Walter Swardfager, Che-Yuan Wu, Mario Masellis, Liisa A M Galea, Katherine Zukotynski, Gillian Einstein, Sandra E Black, Lisa L Barnes, Julie A Schneider, Zoe Arvanitakis, Kaitlin B Casaletto, Jennifer S Rabin
{"title":"路易体病与阿尔茨海默病和认知能力下降相关性的性别差异","authors":"Madeline Wood Alexander, D Luke Fischer, Lawren VandeVrede, Emma Nichols, Lei Yu, James R Pike, Walter Swardfager, Che-Yuan Wu, Mario Masellis, Liisa A M Galea, Katherine Zukotynski, Gillian Einstein, Sandra E Black, Lisa L Barnes, Julie A Schneider, Zoe Arvanitakis, Kaitlin B Casaletto, Jennifer S Rabin","doi":"10.1002/ana.27308","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate how sex and age at menopause influence the interplay between Alzheimer's disease (AD) and Lewy body disease (LBD) neuropathologies, and their associations with cognitive decline.</p><p><strong>Methods: </strong>We analyzed data from: (1) three Rush Alzheimer's Disease Center cohorts (i.e., the Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study), and (2) the National Alzheimer's Coordinating Center Neuropathology Data Set. Neuropathological evaluation assessed LBD (neocortical/limbic-type vs none) and AD, including neuritic plaques (β-amyloid plaques surrounded by dystrophic neurites) and neurofibrillary tangles. In each dataset, we tested interactive associations between LBD and sex on neuritic plaques, neurofibrillary tangles, and cognitive decline. Additionally, in the Rush dataset, we tested whether age at spontaneous menopause modified the associations of LBD with neuritic plaques, neurofibrillary tangles, and cognitive decline in women.</p><p><strong>Results: </strong>In the Rush dataset, we included 1,277 women and 579 men. In the National Alzheimer's Coordinating Center dataset, we included 3,283 women and 3,563 men. Across both datasets, men were more likely to have LBD, whereas women showed greater neuritic plaque and neurofibrillary tangle burdens. Sex modified the associations of LBD with neurofibrillary tangles (but not neuritic plaques), whereby LBD was more strongly associated with greater neurofibrillary tangle burden in women than men. Men showed faster LBD-related cognitive decline, whereas women showed faster neurofibrillary tangle-related decline, after adjusting for copathologies (neuritic plaques, neurofibrillary tangles, and LBD, as appropriate). In women, earlier age at menopause exacerbated the associations of LBD with neurofibrillary tangle burden and episodic memory decline.</p><p><strong>Interpretation: </strong>Sex may influence AD and LBD neuropathologies, highlighting the need for precision approaches to dementia prevention and intervention. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline.\",\"authors\":\"Madeline Wood Alexander, D Luke Fischer, Lawren VandeVrede, Emma Nichols, Lei Yu, James R Pike, Walter Swardfager, Che-Yuan Wu, Mario Masellis, Liisa A M Galea, Katherine Zukotynski, Gillian Einstein, Sandra E Black, Lisa L Barnes, Julie A Schneider, Zoe Arvanitakis, Kaitlin B Casaletto, Jennifer S Rabin\",\"doi\":\"10.1002/ana.27308\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To investigate how sex and age at menopause influence the interplay between Alzheimer's disease (AD) and Lewy body disease (LBD) neuropathologies, and their associations with cognitive decline.</p><p><strong>Methods: </strong>We analyzed data from: (1) three Rush Alzheimer's Disease Center cohorts (i.e., the Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study), and (2) the National Alzheimer's Coordinating Center Neuropathology Data Set. Neuropathological evaluation assessed LBD (neocortical/limbic-type vs none) and AD, including neuritic plaques (β-amyloid plaques surrounded by dystrophic neurites) and neurofibrillary tangles. In each dataset, we tested interactive associations between LBD and sex on neuritic plaques, neurofibrillary tangles, and cognitive decline. Additionally, in the Rush dataset, we tested whether age at spontaneous menopause modified the associations of LBD with neuritic plaques, neurofibrillary tangles, and cognitive decline in women.</p><p><strong>Results: </strong>In the Rush dataset, we included 1,277 women and 579 men. In the National Alzheimer's Coordinating Center dataset, we included 3,283 women and 3,563 men. Across both datasets, men were more likely to have LBD, whereas women showed greater neuritic plaque and neurofibrillary tangle burdens. Sex modified the associations of LBD with neurofibrillary tangles (but not neuritic plaques), whereby LBD was more strongly associated with greater neurofibrillary tangle burden in women than men. Men showed faster LBD-related cognitive decline, whereas women showed faster neurofibrillary tangle-related decline, after adjusting for copathologies (neuritic plaques, neurofibrillary tangles, and LBD, as appropriate). In women, earlier age at menopause exacerbated the associations of LBD with neurofibrillary tangle burden and episodic memory decline.</p><p><strong>Interpretation: </strong>Sex may influence AD and LBD neuropathologies, highlighting the need for precision approaches to dementia prevention and intervention. ANN NEUROL 2025.</p>\",\"PeriodicalId\":127,\"journal\":{\"name\":\"Annals of Neurology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.7000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/ana.27308\",\"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":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ana.27308","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 Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline.
Objective: To investigate how sex and age at menopause influence the interplay between Alzheimer's disease (AD) and Lewy body disease (LBD) neuropathologies, and their associations with cognitive decline.
Methods: We analyzed data from: (1) three Rush Alzheimer's Disease Center cohorts (i.e., the Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study), and (2) the National Alzheimer's Coordinating Center Neuropathology Data Set. Neuropathological evaluation assessed LBD (neocortical/limbic-type vs none) and AD, including neuritic plaques (β-amyloid plaques surrounded by dystrophic neurites) and neurofibrillary tangles. In each dataset, we tested interactive associations between LBD and sex on neuritic plaques, neurofibrillary tangles, and cognitive decline. Additionally, in the Rush dataset, we tested whether age at spontaneous menopause modified the associations of LBD with neuritic plaques, neurofibrillary tangles, and cognitive decline in women.
Results: In the Rush dataset, we included 1,277 women and 579 men. In the National Alzheimer's Coordinating Center dataset, we included 3,283 women and 3,563 men. Across both datasets, men were more likely to have LBD, whereas women showed greater neuritic plaque and neurofibrillary tangle burdens. Sex modified the associations of LBD with neurofibrillary tangles (but not neuritic plaques), whereby LBD was more strongly associated with greater neurofibrillary tangle burden in women than men. Men showed faster LBD-related cognitive decline, whereas women showed faster neurofibrillary tangle-related decline, after adjusting for copathologies (neuritic plaques, neurofibrillary tangles, and LBD, as appropriate). In women, earlier age at menopause exacerbated the associations of LBD with neurofibrillary tangle burden and episodic memory decline.
Interpretation: Sex may influence AD and LBD neuropathologies, highlighting the need for precision approaches to dementia prevention and intervention. ANN NEUROL 2025.
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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