主观认知衰退、APOE e4 等位基因与神经认知障碍风险：年龄和性别分层队列研究。
Subjective cognitive decline, APOE e4 allele, and the risk of neurocognitive disorders: Age- and sex-stratified cohort study.
机构信息
Department of Psychiatry, Singapore General Hospital, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
出版信息
Aust N Z J Psychiatry. 2022 Dec;56(12):1664-1675. doi: 10.1177/00048674221079217. Epub 2022 Mar 1.
OBJECTIVE
Subjective cognitive decline and APOE e4 allele (APOE4) are known predictors of mild cognitive impairment and dementia (mild cognitive impairment/dementia), with recent evidence showing interaction between subjective cognitive decline and APOE4 in amplifying the risk of mild cognitive impairment/dementia. However, the literature is unclear whether the interaction effect is seen across various age and sex strata. This study examined the interaction between subjective cognitive decline and APOE4-across different age and sex strata-on the risk of mild cognitive impairment/dementia.
METHODS
This cohort study included 16,221 participants aged ⩾50 years and had normal cognition at baseline. Participants were evaluated for subjective cognitive decline and APOE4 at baseline, and followed-up almost annually for mild cognitive impairment/dementia (median follow-up = 4.5 years). Interaction effects were examined in Cox regression using Relative Excess Risk due to Interaction, stratified by age (⩽70 vs >70 years) and sex.
RESULTS
Subjective cognitive decline and APOE4 were independently associated with mild cognitive impairment/dementia (hazard ratio: 1.4-1.8), with the highest risk when subjective cognitive decline and APOE4 co-occurred (hazard ratio: 2.6). APOE4 amplified the association between subjective cognitive decline and mild cognitive impairment/dementia in (Relative Excess Risk due to Interaction 1.0; 95% confidence interval = [0.3, 1.6]), but not in other age or sex strata. Among older women, half of them developed mild cognitive impairment/dementia by 12.1 years in the absence of subjective cognitive decline or APOE4. This duration shortened to 8.1-10.3 years in the presence of either subjective cognitive decline or APOE4, and to 4.4 years in the presence of both subjective cognitive decline and APOE4. Interaction effect among older women remained consistent when alternate outcomes were used (i.e. mild cognitive impairment and dementia due to Alzheimer's disease; dementia; and Alzheimer's dementia) (Relative Excess Risk due to Interaction 1.2-2.5).
CONCLUSIONS
APOE4 amplifies the association between subjective cognitive decline and neurocognitive disorders in older women, with the findings suggesting the need for further research to delineate underlying neurobiology. APOE4 may potentially have a role in facilitating further risk stratification of older women with subjective cognitive decline in clinical practice.
目的
主观认知下降和 APOEe4 等位基因（APOE4）是轻度认知障碍和痴呆（轻度认知障碍/痴呆）的已知预测因子，最近的证据表明，主观认知下降和 APOE4 之间的相互作用会放大轻度认知障碍/痴呆的风险。然而，文献尚不清楚这种相互作用是否存在于不同的年龄和性别阶层。本研究旨在探讨主观认知下降和 APOE4 在不同年龄和性别阶层之间的相互作用对轻度认知障碍/痴呆的影响。
方法
本队列研究纳入了 16221 名年龄 ⩾50 岁且基线时认知正常的参与者。基线时评估参与者的主观认知下降和 APOE4，并进行近每年一次的轻度认知障碍/痴呆随访（中位随访时间 ⩾4.5 年）。采用 Cox 回归分析评估交互作用，采用相对超额风险比（因交互作用所致）进行分层，分层因素为年龄（ ⩽70 岁与 ⩾70 岁）和性别。
结果
主观认知下降和 APOE4 均与轻度认知障碍/痴呆独立相关（风险比：1.4-1.8），当主观认知下降和 APOE4 同时发生时风险最高（风险比：2.6）。APOE4 放大了主观认知下降与轻度认知障碍/痴呆之间的关联（交互作用的相对超额风险比为 1.0；95%置信区间=[0.3，1.6]），但在其他年龄或性别阶层中则不然。在老年女性中，在没有主观认知下降或 APOE4 的情况下，有一半人在 12.1 年内发展为轻度认知障碍/痴呆。而在存在主观认知下降或 APOE4 时，这一时间缩短至 8.1-10.3 年，而在同时存在主观认知下降和 APOE4 时，这一时间缩短至 4.4 年。当使用其他结果（即阿尔茨海默病引起的轻度认知障碍和痴呆、痴呆、阿尔茨海默病痴呆）时，老年女性的交互作用效应仍然一致（因交互作用所致的相对超额风险比为 1.2-2.5）。
结论
APOE4 放大了主观认知下降与老年女性神经认知障碍之间的关联，这一发现表明需要进一步研究以阐明潜在的神经生物学机制。APOE4 可能在临床实践中为有主观认知下降的老年女性进一步进行风险分层提供帮助。
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