Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Harvard T.H. Chan School of Public Health, Boston, MA, USA.
J Alzheimers Dis. 2021;79(4):1563-1573. doi: 10.3233/JAD-201281.
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.
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.
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.
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.
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. APOEɛ4 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.
载脂蛋白 E（APOE）ɛ4 等位基因与老年人群认知功能障碍和痴呆风险的剂量反应效应有关。然而，其在中年人群中的认知影响尚不清楚。
我们研究了ɛ4 杂合子和纯合子对参与健康大脑计划（HBP）的中年人群和澳大利亚影像学、生物标志物和生活方式（AIBL）研究中老年人群的客观和主观认知的影响。
HBP 参与者（1000 名非携带者；450 名ɛ4 杂合子；50 名ɛ4 纯合子）完成了 Cogstate 简短电池（CBB）的非监督评估、主观认知功能的评分以及唾液样本的采集。AIBL 认知正常参与者（650 名非携带者；204 名ɛ4 杂合子；31 名ɛ4 纯合子）完成了 CBB 的现场评估、主观认知功能的评分以及血液样本的采集。
与ɛ4 杂合子和非携带者相比，中年ɛ4 纯合子的记忆损伤更为明显。当将中年（HBP）和老年（AIBL）人群的数据汇总时，ɛ4 纯合子与记忆损伤的相关性随着年龄的增长而增加。在中年和老年人群中，ɛ4 杂合子在客观和主观认知的任何测量指标上与非携带者均无差异。
ɛ4 纯合子的记忆损伤在 50-60 岁的成年人中是明显的，并且可以通过非监督认知评估来检测到。ɛ4 纯合子的影响随着年龄的增长而增加。APOEɛ4 纯合子对记忆的负面影响早在中年就已经显现，但由于效应的幅度较小，我们的发现支持了在大型队列中使用在线平台来评估这些复杂关系的必要性。
