Losinski Genna M, Key Mickeal N, Vidoni Eric D, Clutton Jonathan, Morris Jill K, Burns Jeffrey M, Watts Amber
Department of Psychology, University of Kansas.
University of Kansas Alzheimer's Disease Center, University of Kansas Medical Center.
medRxiv. 2024 Nov 22:2024.11.21.24317732. doi: 10.1101/2024.11.21.24317732.
Two thirds of Alzheimer's disease (AD) patients are female. Genetic and chronic health risk factors for AD affect females more negatively compared to males.
This exploratory multimodal neuroimaging study aimed to examine sex differences in cognitively unimpaired older adults on: (1) amyloid-β via 18F-AV-45 Florbetapir PET imaging, (2) neurodegeneration via T1 weighted MRI volumetrics, (3) cerebral blood flow via ASL-MRI. We identified AD risk factors including genetic ( genotype status) and health markers (fasting glucose, mean arterial pressure, waist-to-hip ratio, and android and gynoid body fat) associated with neuroimaging outcomes for which we observed sex differences.
Participants were sedentary, amyloid-β positive older adults (N = 112, ages 65-87 years) without evidence of cognitive impairment (CDR = 0).
Multivariate analysis of covariance models adjusted for intracranial volume, age, and years of education demonstrated lower volume ( (7, 102) = 2.67, p = 0.014) and higher blood flow (6, 102) = 4.25, p =<0.001) among females compared to males in regions of interest connected to AD pathology and the estrogen receptor network. We did not observe sex differences in amyloid-β levels. Higher than optimal waist to hip ratio was most strongly associated with lower volume, while higher android fat percentage and ε4 carrier status were most strongly associated with higher blood flow among female participants.
Findings suggest genetic and chronic health risk factors are associated with sex-specific AD neuroimaging biomarkers. Underlying sex-specific biological pathways may explain these findings. Our results highlight the importance of considering sex differences in neuroimaging studies and when developing effective interventions for AD prevention and risk reduction.
三分之二的阿尔茨海默病（AD）患者为女性。与男性相比，AD的遗传和慢性健康风险因素对女性的负面影响更大。
这项探索性多模态神经影像学研究旨在检查认知未受损的老年人在以下方面的性别差异：（1）通过18F-AV-45氟代贝他吡PET成像检测淀粉样β蛋白；（2）通过T1加权MRI容积测量法检测神经退行性变；（3）通过动脉自旋标记MRI检测脑血流量。我们确定了与神经影像学结果相关的AD风险因素，包括遗传因素（基因型状态）和健康指标（空腹血糖、平均动脉压、腰臀比以及男性型和女性型体脂），并观察到了这些因素的性别差异。
参与者为久坐不动、淀粉样β蛋白呈阳性的老年人（N = 112，年龄65 - 87岁），无认知障碍证据（临床痴呆评定量表[CDR]=0）。
经颅内体积、年龄和受教育年限校正的多变量协方差分析模型显示，在与AD病理和雌激素受体网络相关的感兴趣区域中，女性的脑容量低于男性（F(7, 102)=2.67，p = 0.014），脑血流量高于男性（F(6, 102)=4.25，p < 0.001）。我们未观察到淀粉样β蛋白水平的性别差异。在女性参与者中，高于最佳水平的腰臀比与较低的脑容量最密切相关，而较高的男性型脂肪百分比和ε4携带者状态与较高的脑血流量最密切相关。
研究结果表明，遗传和慢性健康风险因素与特定性别的AD神经影像学生物标志物相关。潜在的性别特异性生物学途径可能解释这些结果。我们的结果强调了在神经影像学研究以及制定有效的AD预防和风险降低干预措施时考虑性别差异的重要性。
