IMPORTANCE Female sex is a major risk factor for late-onset Alzheimer disease (AD), and sex hormones have been implicated as a possible protective factor. Neuroimaging studies that evaluated the effects of sex hormones on brain integrity have primarily emphasized neurodegenerative measures rather than amyloid and tau burden. OBJECTIVE We compared cortical amyloid and regional tau positron emission tomography (PET) deposition between cognitively normal males and females. We also compared preclinical AD pathology between females who have and have not used hormone therapy (HT). Finally, we compared the effects of amyloid and tau pathology on cognition, testing for both sex and HT effects. DESIGN, SETTING, AND PARTICIPANTS We analyzed amyloid, tau, and cognition in a cognitively normal cross-sectional cohort of older individuals (n=148) followed at the Knight Alzheimer Disease Research Center. Amyloid and tau PET, medication history, and neuropsychological testing were obtained for each participant. RESULTS Within cognitively normal individuals, there was no difference in amyloid burden by sex. Whether or not we controlled for amyloid burden, female participants had significantly higher tau PET levels than males in multiple regions, including the rostral middle frontal and superior and middle temporal regions. HT accounted for a small reduction in tau PET; however, males still had substantially lower tau PET compared with females. Amyloid PET and tau PET burden were negatively associated with cognitive performance, although increasing amyloid PET did not have a deleterious effect on cognitive performance for women with a history of HT. CONCLUSIONS AND RELEVANCE Regional sex-related differences in tau PET burden may contribute to the disparities in AD prevalence between males and females. The observed decreases tau PET burden in HT users has important implications for clinical practice and trials and deserves future consideration in longitudinal studies.

中文翻译：

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Tau 正电子发射断层扫描 (PET) 的性别相关差异和激素治疗 (HT) 的效果。

重要性 女性是迟发性阿尔茨海默病 (AD) 的主要危险因素，而性激素被认为是一种可能的保护因素。评估性激素对大脑完整性影响的神经影像学研究主要强调神经退行性措施，而不是淀粉样蛋白和 tau 蛋白负担。目的 我们比较了认知正常的男性和女性之间的皮质淀粉样蛋白和区域 tau 正电子发射断层扫描 (PET) 沉积。我们还比较了接受和未接受激素治疗 (HT) 的女性的临床前 AD 病理学。最后，我们比较了淀粉样蛋白和 tau 蛋白病理学对认知的影响，测试了性别和 HT 的影响。设计、环境和参与者 我们在奈特阿尔茨海默病研究中心对认知正常的老年人横断面队列 (n=148) 中的淀粉样蛋白、tau 蛋白和认知进行了分析。每位参与者都获得了淀粉样蛋白和 tau 蛋白 PET、用药史和神经心理学测试。结果 在认知正常的个体中，淀粉样蛋白负荷不存在性别差异。无论我们是否控制淀粉样蛋白负荷，女性参与者在多个区域的 tau PET 水平显着高于男性，包括额叶中段、颞上区和中区。HT 导致 tau PET 略有减少；然而，与女性相比，男性的 tau PET 值仍然显着较低。淀粉样蛋白 PET 和 tau PET 负担与认知能力呈负相关，尽管增加淀粉样蛋白 PET 不会对有 HT 病史的女性的认知能力产生有害影响。结论和相关性 tau PET 负担的区域性别相关差异可能导致男性和女性 AD 患病率的差异。观察到的 HT 用户 tau PET 负担减少对临床实践和试验具有重要意义，值得未来在纵向研究中考虑。