Background:The apolipoprotein E (APOE) ɛ4 allele is associated with dose-response effects on cognitive dysfunction and dementia risk in older adults. However, its effects on cognition in middle-aged adults remains unclear. Objective:We examined effects of ɛ4 heterozygosity and homozygosity on objective and subjective cognition in middle-aged adults enrolled in the Healthy Brain Project (HBP) and in older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Methods:HBP participants (1,000 non-carriers; 450 ɛ4 heterozygotes; 50 ɛ4 homozygotes) completed unsupervised assessments of the Cogstate Brief Battery (CBB), ratings of subjective cognitive function and provided a saliva sample. AIBL cognitively normal participants (650 non-carriers; 204 ɛ4 heterozygotes; 31 ɛ4 homozygotes) completed in-person assessments of the CBB, ratings of subjective cognitive function and provided a blood sample. Results:Greater memory impairment was observed in middle-aged ɛ4 homozygotes compared with ɛ4 heterozygotes and non-carriers. When data from middle-aged (HBP) and older (AIBL) adults were pooled, the effect of ɛ4 homozygosity and memory impairment increased with age. In both middle-aged and older adults, ɛ4 heterozygotes did not differ from non-carriers on any measure of objective or subjective cognition. Conclusion:Memory impairment in ɛ4 homozygotes is evident in adults aged 50-60 years, and this can be detected through unsupervised cognitive assessments. The effect of ɛ4 homozygosity increases with older age. APOE ɛ4 homozygosity has a negative impact on memory as early as midlife, but due to the subtle magnitude of effect, our findings support the necessity of online platforms in large cohorts to assess these complex relationships.

中文翻译：

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使用无监督认知评估检测到中年 APOE ɛ4 纯合子的视觉记忆缺陷

背景：载脂蛋白 E (APOE) ɛ4 等位基因与老年人认知功能障碍和痴呆风险的剂量反应效应相关。然而，其对中年人认知的影响尚不清楚。目的：我们研究了 ɛ4 杂合性和纯合性对参加健康大脑项目 (HBP) 的中年人和来自澳大利亚成像、生物标志物和生活方式 (AIBL) 研究的老年人的客观和主观认知的影响。方法：HBP 参与者（1,000 个非携带者；450 个 ɛ4 杂合子；50 个 ɛ4 纯合子）完成了 Cogstate Brief Battery (CBB) 的无监督评估、主观认知功能的评级并提供了唾液样本。AIBL 认知正常的参与者（650 名非携带者；204 ɛ4 杂合子；31 ɛ4 纯合子）完成了 CBB 的面对面评估，主观认知功能评级并提供血样。结果：与 ɛ4 杂合子和非携带者相比，在中年 ɛ4 纯合子中观察到更大的记忆障碍。当汇集来自中年 (HBP) 和老年人 (AIBL) 的数据时，ɛ4 纯合子和记忆障碍的影响随着年龄的增长而增加。在中年人和老年人中，ɛ4 杂合子在任何客观或主观认知方面都与非携带者没有区别。结论：ɛ4纯合子的记忆障碍在50-60岁的成年人中很明显，这可以通过无监督的认知评估来检测到。ɛ4 纯合性的影响随着年龄的增长而增加。APOE ɛ4 纯合性早在中年就对记忆产生负面影响，但由于影响的微妙程度，