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Cognitive Decline in Alzheimer’s Disease Is Not Associated with APOE
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2021-08-30 , DOI: 10.3233/jad-210685
Ioanna Katzourou 1 , Ganna Leonenko 1 , Dobril Ivanov 1 , Alun Meggy 2 , Rachel Marshall 2 , Rebecca Sims 2 , Julie Williams 1 , Peter Holmans 2 , Valentina Escott-Price 1 ,
Affiliation  

Background:The rate of cognitive decline in Alzheimer’s disease (AD) has been found to vary widely between individuals, with numerous factors driving this heterogeneity. Objective:This study aimed to compute a measure of cognitive decline in patients with AD based on clinical information and to utilize this measure to explore the genetic architecture of cognitive decline in AD. Methods:An in-house cohort of 616 individuals, hereby termed the Cardiff Genetic Resource for AD, as well as a subset of 577 individuals from the publicly available ADNI dataset, that have been assessed at multiple timepoints, were used in this study. Measures of cognitive decline were computed using various mixed effect linear models of Mini-Mental State Examination (MMSE). After an optimal model was selected, a metric of cognitive decline for each individual was estimated as the random slope derived from this model. This metric was subsequently used for testing the association of cognitive decline with apolipoprotein E (APOE) genotype. Results:No association was found between the number of APOE ɛ2 or ɛ4 alleles and the rate of cognitive decline in either of the datasets examined. Conclusion:Further exploration is required to uncover possible genetic variants that affect the rate of decline in patients with AD.

中文翻译:

阿尔茨海默病的认知衰退与 APOE 无关

背景:已发现阿尔茨海默氏病 (AD) 的认知衰退率在个体之间存在很大差异,许多因素导致了这种异质性。目的:本研究旨在根据临床信息计算 AD 患者认知能力下降的指标,并利用该指标探索 AD 认知能力下降的遗传结构。方法:本研究使用了一个由 616 名个体组成的内部队列,特此称为 AD 的卡迪夫遗传资源,以及来自公开可用的 ADNI 数据集的 577 名个体的子集,这些数据集已在多个时间点进行了评估。使用简易精神状态检查 (MMSE) 的各种混合效应线性模型计算认知衰退的测量值。选择最优模型后,每个人的认知衰退指标被估计为从该模型得出的随机斜率。该指标随后用于测试认知能力下降与载脂蛋白 E (APOE) 基因型的关联。结果:在所检查的任一数据集中,APOE ɛ2 或 ɛ4 等位基因的数量与认知能力下降率之间没有关联。结论:需要进一步探索以揭示可能影响 AD 患者衰退率的遗传变异。
更新日期:2021-09-01
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