Institute for Regenerative Medicine - IREM, University of Zurich, Zurich, Switzerland.
Women's Brain Project, Guntershausen, Switzerland.
Eur J Neurol. 2020 Jun;27(6):928-943. doi: 10.1111/ene.14174. Epub 2020 Apr 3.
Alzheimer's disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual's sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.
阿尔茨海默病（AD）的临床表现、进展和危险因素存在高度异质性。目前，高表型变异性被认为是早期诊断和临床试验设计的最大障碍之一；因此，人们非常关注识别驱动变异性的因素，这些因素可用于患者分层。除了遗传和生活方式因素外，个体的性别也成为表型变异性的关键驱动因素。在认知恶化和脑萎缩的速度、风险因素的影响以及诊断生物标志物的模式方面，都存在关于性别差异的证据。这些证据可能具有重要意义，在临床实践和临床试验中需要加以关注。然而，目前很少有人意识到性别差异；重要的是，在 AD 的临床试验设计和分析中，目前并未关注性别差异。本立场文件的目的是：(i) 概述可能对临床实践有影响的已知性别差异；(ii) 确定该领域最重要的知识空白（特别是临床试验）；(iii) 为未来的研究提供结论。本科学声明得到了欧洲神经病学会的认可。
