Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer’s disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged apolipoprotein ε4 carriers (APOEε4+) were investigated. Longitudinal 3 T T1-weighted and arterial spin labelling MRI data from 158 participants (40–59 years old) in the PREVENT-Dementia study were analysed (125 two-year follow-up). Cognition was evaluated using the COGNITO battery. Cerebral blood flow (CBF) and cerebrovascular resistance index (CVRi) were quantified for the flow territories of the anterior, middle and posterior cerebral arteries. CBF was corrected for underlying atrophy and individual hematocrit. Hemodynamic measures were the dependent variables in linear regression models, with age, sex, years of education and APOEε4 carriership as predictors. Further analyses were conducted with cognitive outcomes as dependent variables, using the same model as before with additional APOEε4 × hemodynamics interactions. At baseline, APOEε4+ showed increased CBF and decreased CVRi compared to non-carriers in the anterior and middle cerebral arteries, suggestive of potential vasodilation. Hemodynamic changes were similar between groups. Interaction analysis revealed positive associations between CBF changes and performance changes in delayed recall (for APOEε4 non-carriers) and verbal fluency (for APOEε4 carriers) cognitive tests. These observations are consistent with neurovascular dysregulation in middle-aged APOEε4+.

越来越多的证据表明临床前阿尔茨海默病存在血管失调。本研究对中年载脂蛋白ε4携带者（APOEε4+）的脑血流动力学及其与认知的耦合进行了研究。对 PREVENT-Dementia 研究中 158 名参与者（40-59 岁）的纵向 3 T T1 加权和动脉自旋标记 MRI 数据进行了分析（125 名参与者进行了两年随访）。使用 COGNITO 电池评估认知能力。对大脑前动脉、中动脉和后动脉的血流区域的脑血流量（CBF）和脑血管阻力指数（CVRi）进行量化。针对潜在萎缩和个体血细胞比容校正 CBF。血流动力学测量是线性回归模型中的因变量，以年龄、性别、受教育年限和 APOEε4 携带作为预测因子。使用与之前相同的模型以及额外的 APOEε4 × 血流动力学相互作用，以认知结果作为因变量进行进一步分析。在基线时，与非携带者相比，APOEε4+ 在大脑前动脉和中动脉中表现出 CBF 增加和 CVRi 降低，提示潜在的血管舒张。各组之间的血流动力学变化相似。交互分析显示，CBF 变化与延迟回忆（对于 APOEε4 非携带者）和言语流畅性（对于 APOEε4 携带者）认知测试中的表现变化呈正相关。这些观察结果与中年 APOEε4+ 的神经血管失调一致。