路易体病与阿尔茨海默病及认知衰退关联中的性别差异

Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline.

作者信息

Wood Alexander Madeline, Fischer D Luke, VandeVrede Lawren, Nichols Emma, Yu Lei, Pike James R, Swardfager Walter, Wu Che-Yuan, Masellis Mario, Galea Liisa A M, Zukotynski Katherine, Einstein Gillian, Black Sandra E, Barnes Lisa L, Schneider Julie A, Arvanitakis Zoe, Casaletto Kaitlin B, Rabin Jennifer S

机构信息

Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.

Rehabilitation Sciences Institute, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

出版信息

Ann Neurol. 2025 Jul 11. doi: 10.1002/ana.27308.

DOI:10.1002/ana.27308

PMID:40646704

Abstract

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.

摘要

目的

研究绝经时的性别和年龄如何影响阿尔茨海默病（AD）和路易体病（LBD）神经病理学之间的相互作用，以及它们与认知衰退的关联。

方法

我们分析了来自以下两方面的数据：（1）三个拉什阿尔茨海默病中心队列（即宗教团体研究、拉什记忆与衰老项目以及少数族裔衰老研究），以及（2）国家阿尔茨海默病协调中心神经病理学数据集。神经病理学评估包括LBD（新皮质/边缘型与无LBD）和AD，其中AD包括神经炎性斑块（由营养不良性神经突包围的β淀粉样蛋白斑块）和神经原纤维缠结。在每个数据集中，我们测试了LBD与性别在神经炎性斑块、神经原纤维缠结和认知衰退方面的交互关联。此外，在拉什数据集中，我们测试了自然绝经年龄是否改变了LBD与女性神经炎性斑块、神经原纤维缠结和认知衰退之间的关联。

结果

在拉什数据集中，我们纳入了1277名女性和579名男性。在国家阿尔茨海默病协调中心数据集中，我们纳入了3283名女性和3563名男性。在两个数据集中，男性患LBD的可能性更高，而女性的神经炎性斑块和神经原纤维缠结负担更重。性别改变了LBD与神经原纤维缠结（而非神经炎性斑块）之间的关联，即与男性相比，LBD在女性中与更严重的神经原纤维缠结负担关联更强。在调整共存病变（酌情包括神经炎性斑块、神经原纤维缠结和LBD）后，男性显示出与LBD相关的更快认知衰退，而女性显示出与神经原纤维缠结相关的更快衰退。在女性中，更早的绝经年龄加剧了LBD与神经原纤维缠结负担和情景记忆衰退之间的关联。