AXA Research Fund & Sorbonne University Chair, Paris, France; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
AXA Research Fund & Sorbonne University Chair, Paris, France; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
Alzheimers Dement. 2018 Sep;14(9):1204-1215. doi: 10.1016/j.jalz.2018.05.014. Epub 2018 Jul 7.
Observational multimodal neuroimaging studies indicate sex differences in Alzheimer's disease pathophysiological markers.
Positron emission tomography brain amyloid load, neurodegeneration (hippocampus and basal forebrain volumes adjusted to total intracranial volume, cortical thickness, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose-positron emission tomography metabolism), and brain resting-state functional connectivity were analyzed in 318 cognitively intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117). A linear mixed-effects model was performed to investigate sex effects and sex∗apolipoprotein E genotype interaction on each marker as well as sex∗amyloid group interaction for non-amyloid markers.
Men compared with women showed higher anterior cingulate cortex amyloid load (P = .009), glucose hypometabolism in the precuneus (P = .027), posterior cingulate (P < .001) and inferior parietal (P = .043) cortices, and lower resting-state functional connectivity in the default mode network (P = .024). No brain volumetric markers showed differences between men and women. Sex∗apolipoprotein E genotype and sex∗amyloid status interactions were not significant.
Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.
观察性多模态神经影像学研究表明，阿尔茨海默病病理生理标志物存在性别差异。
对来自 INSIGHT-preAD 队列的 318 名认知正常的老年人（女性 n=201，男性 n=117）进行正电子发射断层扫描脑淀粉样蛋白负荷、神经退行性变（海马和基底前脑体积调整为总颅内体积、皮质厚度和 2-脱氧-2-[氟-18]氟-D-葡萄糖正电子发射断层扫描代谢）以及脑静息态功能连接的分析。采用线性混合效应模型，研究性别对每种标志物的影响以及性别与载脂蛋白 E 基因型的相互作用，以及非淀粉样标志物的性别与淀粉样蛋白组的相互作用。
与女性相比，男性的前扣带回皮质淀粉样蛋白负荷更高（P=0.009），楔前叶（P=0.027）、后扣带回（P<0.001）和下顶叶（P=0.043）皮质的葡萄糖代谢更低，以及默认模式网络的静息态功能连接更低（P=0.024）。男性和女性的脑容量标志物无差异。性别与载脂蛋白 E 基因型和性别与淀粉样蛋白状态的相互作用不显著。
我们的发现表明，与女性相比，认知正常的老年男性对阿尔茨海默病的病理生理过程有更高的适应能力。
