Department of Neurology, Lou Ruvo Center for Brain Health, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 9500 Euclid Ave / U10, Cleveland, OH, 44195, USA.
Cleveland Clinic, Neurological Institute, Cleveland, OH, 44195, USA.
Alzheimers Res Ther. 2021 Jan 23;13(1):31. doi: 10.1186/s13195-021-00771-1.
APOE ε4 carrier status is known to increase odds of amnestic presentations with Alzheimer's pathology. It is unknown how APOE ε4 carrier status impacts odds of specific initial cognitive symptoms in the presence of Lewy body pathology. Here we evaluate the impact of APOE ε4 genotype on initial cognitive symptoms among those with Alzheimer's disease pathology (ADP) and Lewy-related pathology (LRP).
A retrospective cohort study of 2288 participants with neuropathology confirmed ADP or LRP in the National Alzheimer's Coordinating Center database, who had initial cognitive symptoms documented and had a Clinical Dementia Rating-Global (CDR-G) score ≤ 1 (cognitively normal, MCI, or early dementia). Unadjusted and adjusted logistic regression models taking into account age at evaluation, sex, and education examined the relationship between APOE ε4 genotype and initial symptoms (memory, executive, language visuospatial) among ADP with LRP and ADP-LRP groups.
One thousand three hundred three participants met criteria for ADP alone, 90 for LRP alone, and 895 for co-existing ADP and LRP (ADP-LRP). Younger age increased odds of non-amnestic symptoms across all three groups. In the adjusted model among ADP, APOE ε4 carriers had higher odds of amnestic initial symptoms 1.5 [95% CI, 1.7-2.14, p = 0.003] and lower odds of initial language symptoms 0.67 [95% CI, 0.47-0.96, p = 0.03] than non-carriers. The odds for these two symptoms were not different between ADP and mixed ADP-LRP groups. Female sex and higher education increased odds of initial language symptoms in the ADP group in the adjusted model. In the unadjusted model, APOE ε4 carriers with LRP had a higher odds of visuospatial initial symptoms 21.96 [95% CI, 4.02-110.62, p < 0.0001], while no difference was noted for initial executive/attention symptoms. Among LRP, the odds of APOE ε4 on amnestic symptom was not significant; however, the interaction effect evaluating the difference in odds ratios of amnestic symptom between ADP and LRP groups also did not reach statistical significance.
The odds of specific initial cognitive symptoms differed between ADP and LRP among APOE ε4 carriers compared to non-carriers. The odds of initial amnestic symptom was higher among ADP APOE ε4 carriers and the odds of visuospatial initial symptom was higher with LRP APOE ε4 carriers. This supports the hypothesis that APOE ε4 differentially impacts initial cognitive symptoms together with underlying neuropathology.
载脂蛋白 E ε4 等位基因的存在已知会增加阿尔茨海默病病理的遗忘型表现的几率。目前尚不清楚载脂蛋白 E ε4 等位基因对路易体病理存在时的特定初始认知症状的几率有何影响。在这里，我们评估了载脂蛋白 E ε4 基因型对国家阿尔茨海默病协调中心数据库中神经病理学证实为阿尔茨海默病病理学（ADP）和路易体相关病理学（LRP）患者的初始认知症状的影响。
对 2288 名参与者进行了回顾性队列研究，这些参与者的神经病理学在国家阿尔茨海默病协调中心数据库中证实为 ADP 或 LRP，他们有初始认知症状记录，且临床痴呆评定-全球量表（CDR-G）评分为≤1（认知正常、MCI 或早期痴呆）。未调整和调整后的逻辑回归模型考虑了评估时的年龄、性别和教育，以检查 ADP 伴 LRP 和 ADP-LRP 组中 APOE ε4 基因型与初始症状（记忆、执行、语言、视空间）之间的关系。
1303 名参与者符合 ADP 单独的标准，90 名符合 LRP 单独的标准，895 名符合 ADP 和 LRP 并存（ADP-LRP）的标准。所有三组中，年龄较小都会增加非遗忘症状的几率。在 ADP 的调整模型中，载脂蛋白 E ε4 携带者出现遗忘性初始症状的几率更高 1.5 [95%CI，1.7-2.14，p=0.003]，出现初始语言症状的几率更低 0.67 [95%CI，0.47-0.96，p=0.03]，而非携带者。在 ADP 和混合 ADP-LRP 组之间，这两种症状的几率没有差异。在调整模型中，女性和较高的教育程度会增加 ADP 组中初始语言症状的几率。在未调整的模型中，LRP 中的载脂蛋白 E ε4 携带者出现视空间初始症状的几率更高 21.96 [95%CI，4.02-110.62，p<0.0001]，而初始执行/注意力症状则没有差异。在 LRP 中，APOE ε4 对遗忘症状的几率没有统计学意义；然而，评估 ADP 和 LRP 组之间遗忘症状比值比差异的交互效应也没有达到统计学意义。
与非携带者相比，载脂蛋白 E ε4 携带者的 ADP 和 LRP 之间的特定初始认知症状的几率不同。ADP 载脂蛋白 E ε4 携带者的初始遗忘症状几率较高，而 LRP 载脂蛋白 E ε4 携带者的初始视空间症状几率较高。这支持了载脂蛋白 E ε4 与潜在的神经病理学一起对初始认知症状有不同影响的假设。
