绝经期激素治疗与阿尔茨海默病神经病理学之间的关联
Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology.
摘要(中文译文)
尽管有证据表明绝经期雌激素水平下降的神经生理学影响可能导致女性阿尔茨海默病（AD）风险增加，但绝经激素治疗（MHT）对AD风险的影响仍需进一步研究。我们试图探讨MHT使用与神经病理学、临床及影像/液体生物标志物结局之间的关联。在这项队列研究中，我们使用两个独立的大规模数据集——国家阿尔茨海默病协调中心（NACC）和阿尔茨海默病神经影像学倡议（ADNI）——检验了单纯雌激素MHT使用与女性参与者痴呆结局之间的关联。参与者包括50岁及以上、自我报告使用单纯雌激素MHT或自我报告未使用MHT的女性。研究检查了临床、影像/液体生物标志物及神经病理学结局。研究在学术医学中心进行。神经病理学数据来自NACC，包括258名MHT使用者（平均死亡年龄=81.9，SD=19.5）和2,701名非MHT使用者（平均死亡年龄=82.2，SD=11.0）。ADNI队列包括110名MHT使用者（平均年龄=76.5，SD=7.5）和1,948名非MHT使用者（平均年龄=73.2，SD=8.9）。与未使用者相比，MHT使用者尸检时AD病理增加的优势比（主要结局）显著降低（优势比[OR] 0.65，95% CI 0.48-0.88，= 0.005）。MHT使用与次要结局相关，包括通过血浆（β = 0.44，95% CI 0.16-0.73，= 0.0025）和脑脊液（β = 0.07，95% CI 0.002-0.13，= 0.030）评估的淀粉样蛋白病理负荷显著降低。MHT使用与临床痴呆诊断优势比显著降低（OR 0.61，95% CI 0.55-0.67，< 0.0001）以及记忆/功能下降症状优势比降低（OR 0.67，95% CI 0.61-0.74，< 0.0001）相关。我们的研究结果表明，在两个大型女性参与者队列中，晚年MHT使用与一系列AD相关神经病理学和临床结局之间存在小而显著的关联。尽管我们的结果未涉及因果关系，且由于研究的回顾性性质而推广性有限，但它们提示MHT使用在痴呆病程中具有保护作用。
Abstract
Although evidence suggests that the neurophysiologic impact of estrogen decline during menopause may contribute to increased risk of Alzheimer disease (AD) in women, the effect of menopausal hormonal therapy (MHT) on AD risk requires further study. We sought to examine the associations between MHT use and neuropathologic, clinical, and imaging/fluid biomarker outcomes. In this cohort study, we tested the association between estrogen-only MHT use and dementia outcomes in female participants using 2 independent, large-scale data sets: National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants included women 50 years and older with self-reported use of estrogen-only MHT or no self-reported use of MHT. Clinical, imaging/fluid biomarker, and neuropathologic outcomes were examined. Research was performed at academic medical centers. Neuropathologic data were collected from NACC for 258 MHT users (mean age of death = 81.9, SD = 19.5) and 2,701 non-MHT users (mean age of death = 82.2, SD = 11.0). The ADNI cohort included 110 MHT users (mean age = 76.5, SD = 7.5) and 1,948 non-MHT users (mean age = 73.2, SD = 8.9). The odds of increased AD pathology on autopsy (primary outcome) were significantly decreased in MHT users relative to nonusers (odds ratio [OR] 0.65, 95% CI 0.48-0.88, = 0.005). MHT use was associated with secondary outcomes including significantly decreased amyloid pathologic load assessed through plasma (β = 0.44, 95% CI 0.16-0.73, = 0.0025) and CSF (β = 0.07, 95% CI 0.002-0.13, = 0.030). MHT use was associated with significantly lower odds of clinical dementia diagnoses (OR 0.61, 95% CI 0.55-0.67, < 0.0001) and lower odds of symptoms of memory/functional decline (OR 0.67, 95% CI 0.61-0.74, < 0.0001). Our findings demonstrate small but significant associations between MHT use during later life and a range of AD-related neuropathologic and clinical outcomes in 2 large cohorts of female participants. Although our results do not address causality and have limited generalizability due to the retrospective nature of the study, they suggest a protective effect of MHT use in the dementia course.
如何引用
AMA
Jennifer Bruno, Jacob S Shaw, S M Hadi Hosseini. Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology.. Neurology. 2026; doi:10.1212/WNL.0000000000218413.
APA
Jennifer Bruno, Jacob S Shaw, S M Hadi Hosseini (2026). Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology.. Neurology. https://doi.org/10.1212/WNL.0000000000218413
GB/T 7714
Jennifer Bruno, Jacob S Shaw, S M Hadi Hosseini. Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology.[J]. Neurology, 2026 doi:10.1212/WNL.0000000000218413.
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