Chooi Cheyenne, Gavett Brandon E, Ames David, Maruff Paul, Doré Vincent, Villemagne Victor L, Bourgeat Pierrick, Xia Ying, Masters Colin L, Martins Ralph N, Taddei Kevin, Rowe Christopher C, Weinborn Michael, Rainey-Smith Stephanie R
School of Psychological Science, University of Western Australia, 35 Stirling Highway, Crawley, Western Australia, Australia.
Department of Psychology, University of California, Davis, CA, USA.
Aging Brain. 2025 Jul 31;8:100146. doi: 10.1016/j.nbas.2025.100146. eCollection 2025.
Sex differences in cognitive reserve might contribute to females being disproportionately affected by Alzheimer's disease (AD). We investigated sex differences in the protective effects of cognitive reserve, and whether brain beta-amyloid accounts for differences. Older adults (n = 997 from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing) diagnosed as Cognitively Normal, Mild Cognitive Impairment, or AD at baseline were assessed every 18 months for up to a maximum of seven visits. Cognitive reserve was calculated from the variance in episodic memory not explained by demographic or brain measures. Executive functioning (EF) intercept and slope were regressed onto the main and interaction effects of cognitive reserve x brain integrity x sex, plus covariates (age, number of ε4 alleles). A three-way interaction was observed between cognitive reserve, brain integrity, and sex on the EF slope. Females benefitted more than males from the protective effects of cognitive reserve at low levels of brain integrity. Sex differences in the protective effect of cognitive reserve were not moderated by brain beta-amyloid burden.
认知储备方面的性别差异可能导致女性受阿尔茨海默病（AD）的影响尤为严重。我们研究了认知储备保护作用中的性别差异，以及脑β-淀粉样蛋白是否是造成这些差异的原因。对年龄较大的成年人（来自澳大利亚衰老成像、生物标志物和生活方式研究的997人）进行研究，这些人在基线时被诊断为认知正常、轻度认知障碍或AD，每18个月评估一次，最多评估七次。认知储备通过情景记忆的方差计算得出，该方差不能由人口统计学或脑部测量指标解释。将执行功能（EF）截距和斜率回归到认知储备×脑完整性×性别的主效应和交互效应，以及协变量（年龄、ε4等位基因数量）上。在EF斜率上观察到认知储备、脑完整性和性别之间存在三向交互作用。在脑完整性水平较低时，女性从认知储备的保护作用中受益比男性更多。认知储备保护作用的性别差异不受脑β-淀粉样蛋白负担的调节。
