Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Center for Demography of Health and Aging, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Alzheimers Dement. 2023 Jul;19(7):3108-3118. doi: 10.1002/alz.12920. Epub 2023 Feb 1.
We sought to characterize the timing of changes in cognitive trajectories related to genetic risk using the apolipoprotein E (APOE) score, a continuous measure of Alzheimer's disease (AD) risk. We also aimed to determine whether that timing was different when genetic risk was measured using an AD polygenic risk score (PRS) that contains APOE.
We analyzed trajectories (N ≈1135) for four neuropsychological composite scores using mixed effects regression for longitudinal change across APOE scores and PRS of participants in the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of adults aged 40 to 70 at baseline, with a median participant follow-up time of 7.8 years.
We found a significant non-linear age-by-APOE score interaction in predicting cognitive decline. Cognitive trajectories diverged by APOE score at approximately 65 years of age. A 0.5 standard deviation difference in cognition between extreme percentiles of the PRS was predicted to occur 1 to 2 years before that of the APOE score.
Cognitive decline differs across time and APOE score. Estimates did not substantially shift with the AD PRS.
The apolipoprotein E (APOE) score, a continuous measure, accounts for non-linear genetic risk of Alzheimer's disease. Non-linear age interacts with the APOE score to affect cognition. Cognitive decline starts to differ by APOE score levels at approximately age 65. Cognitive decline timing by polygenic risk (including APOE) is similar to APOE alone.
我们试图通过载脂蛋白 E (APOE) 评分来描述与遗传风险相关的认知轨迹变化的时间，APOE 评分是阿尔茨海默病 (AD) 风险的连续衡量标准。我们还旨在确定当使用包含 APOE 的 AD 多基因风险评分 (PRS) 测量遗传风险时，这种时间是否不同。
我们使用混合效应回归分析了来自威斯康星州阿尔茨海默病预防注册研究的参与者的四个神经心理学综合评分的轨迹（N ≈1135），该研究是一项针对基线年龄为 40 至 70 岁的成年人的纵向研究，中位随访时间为 7.8 年。
我们发现年龄与 APOE 评分之间存在显著的非线性交互作用，可预测认知下降。认知轨迹在大约 65 岁时根据 APOE 评分而分化。PRS 极端百分位之间的认知差异预计会在 APOE 评分之前 1 至 2 年出现。
认知下降在时间和 APOE 评分上有所不同。使用 AD PRS 后，估计值并未发生实质性变化。
载脂蛋白 E (APOE) 评分是一种连续的衡量标准，可解释阿尔茨海默病的非线性遗传风险。非线性年龄与 APOE 评分相互作用影响认知。大约在 65 岁左右，认知下降开始根据 APOE 评分水平而有所不同。多基因风险（包括 APOE）的认知下降时间与 APOE 单独相似。
