Apolipoprotein E genotype does not moderate the associations of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive aging in the Lothian Birth Cohort 1936

ObjectivesIn this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes.MethodsWe used data from the Lothian Birth Cohort 1936 (n at Waves 1–3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659 [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of general cognitive ability (modeled using five cognitive tests) with groups of APOE E4 non-carriers and carriers. In separate models, depressive symptoms, neuroticism, and allostatic load predicted baseline cognitive ability and subsequent cognitive decline. In addition, models tested whether allostatic load mediated relationships between neuroticism and cognitive outcomes.ResultsBaseline cognitive ability had small-to-moderate negative associations with depressive symptoms (β range = -0.20 to -0.17), neuroticism (β range = -0.27 to -0.23), and allostatic load (β range = -0.11 to 0.09). Greater cognitive decline was linked to baseline allostatic load (β range = -0.98 to -0.83) and depressive symptoms (β range = -1.00 to -0.88). However, APOE E4 allele possession did not moderate the relationships of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive decline. Additionally, the associations of neuroticism with cognitive ability and cognitive decline were not mediated through allostatic load.ConclusionsOur results suggest that APOE E4 status does not moderate the relationships of depressive symptoms, neuroticism, and allostatic load with cognitive ability and cognitive decline in healthy older adults. The most notable positive finding in the current research was the strong association between allostatic load and cognitive decline.

研究目的：本项复制与拓展研究旨在检验老年群体中，抑郁症状、神经质与稳态负荷（allostatic load，即多系统生理失调）是否与较低的基线认知能力及更快的后续认知衰退相关，并探究载脂蛋白E（apolipoprotein E, APOE）基因的E4等位基因（E4 allele）是否对上述关联存在调节作用。此外，本研究还检验了稳态负荷是否中介神经质与认知结局之间的关联。
研究方法：本研究使用洛锡安出生队列1936（Lothian Birth Cohort 1936）的数据，第1至3波的有效样本量分别为1028例[平均年龄=69.5岁]、820例[自第1波起平均随访时长=2.98年]、659例[自第1波起平均随访时长=6.74年]。我们针对APOE E4非携带者与携带者群体，构建了基于五项认知测验建模的一般认知能力的潜增长曲线模型。在独立模型中，分别以抑郁症状、神经质与稳态负荷预测基线认知能力及后续认知衰退；此外，部分模型检验了稳态负荷是否介导神经质与认知结局之间的关联。
研究结果：基线认知能力与抑郁症状（β系数范围：-0.20至-0.17）、神经质（β系数范围：-0.27至-0.23）及稳态负荷（β系数范围：-0.11至0.09）呈小至中等程度的负相关。更快的认知衰退与基线稳态负荷（β系数范围：-0.98至-0.83）及抑郁症状（β系数范围：-1.00至-0.88）相关。但APOE E4等位基因携带情况并未调节抑郁症状、神经质与稳态负荷分别与认知能力及认知衰退之间的关联。此外，神经质与认知能力、认知衰退之间的关联并未通过稳态负荷实现中介。
研究结论：本研究结果表明，在健康老年群体中，APOE E4基因型并未调节抑郁症状、神经质与稳态负荷分别与认知能力及认知衰退之间的关联。本研究最具意义的阳性发现为稳态负荷与认知衰退之间存在强关联。