Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age‐related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE‐ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion‐weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE‐ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.

中文翻译：

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心血管危险因素和 APOE-ε4 状态通过时间干扩散的变化影响衰老过程中的记忆功能

先前调查高血压、肥胖和载脂蛋白 ( APOE ) 基因型状态与老年人记忆能力之间关联的研究产生了不一致的结果。这可能部分反映了缺乏首先考虑这些变量对结构性大脑变化的影响，这反过来又会导致与年龄相关的记忆障碍。目前的研究试图通过路径建模来阐明这些因素之间的关系。我们假设较高的体重指数 (BMI)、高血压和APOE‐ε4 等位基因携带者会预测较差的记忆评分，其中大部分影响是由通过颞干白质完整性差异产生的间接影响来解释的。参与者包括 125 名接受神经心理学评估和弥散加权 MRI 扫描的健康老年人。发现了高血压和人口统计学变量（包括年龄、性别和教育）的直接影响。重要的是，发现了对 BMI、高血压、APOE 的间接影响‐ε4 状态、年龄和性别，这些因素通过它们对时间词干扩散测量的影响来预测记忆分数。性别也有双重效应，直接效应表明女性总体上具有更好的记忆性能，间接效应表明具有较大时间词干扩散的女性具有较差的记忆性能。结果表明，衰老过程中颞白质完整性的变化可能会导致记忆力下降。这些结果强调，解释不仅直接影响认知的变量，而且解释那些通过结构性大脑变化间接影响认知的变量，对于理解风险因素对认知的影响至关重要。