Objective: White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer’s disease (AD) risk. Method: The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131). Results: After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume. Conclusions: These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.

中文翻译：

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健康老龄化过程中年龄和载脂蛋白 E ε4 状态对局部白质高信号体积和认知的影响

目的：白质高信号（WMH）体积是与小血管疾病相关的病变负荷的神经影像学标志物，该疾病与认知衰老和阿尔茨海默病（AD）风险相关。方法：本研究旨在探讨区域 WMH 体积是否介导 APOE ε4 状态（AD 的强遗传风险因素）与认知之间的关系，以及这种关联是否受到 187 名健康老年人样本中年龄组差异的调节（APOE ε4 状态[运营商/非运营商] = 56/131)。结果：在我们控制了性别、教育程度和血管危险因素后，ANCOVA 分析显示，右顶叶和左颞叶 WMH 体积的 APOE ε4 状态相互作用存在显着的年龄组差异。在年轻老年组（50-69岁）中，ε4携带者的右顶叶和左颞叶WMH体积比非携带者更大。然而，在老年组（70-89 岁）中，APOE ε4 组的右顶叶和左颞叶 WMH 体积相当。此外，在ε4非携带者中，老年人的右顶叶和左颞WMH体积比年轻老年人更大，但ε4携带者中不同年龄组之间没有显着差异。后续调节中介分析显示，在年轻组中，ε4 状态通过左颞 WMH 体积对记忆和执行功能有显着的间接影响，但在老年组中则不然。结论：这些研究结果表明，在健康的年轻老年人中，在 ε4 等位基因的背景下，左颞 WMH 体积增加可能代表认知衰老的早期标志，并有可能导致 AD 风险增加。