From the Department of Psychiatry (Y.J.L., D.Y.L.), Seoul National University College of Medicine (J.Y.H.); Medical Research Center, Institute of Human Behavioral Medicine (M.S.B., D.Y.L.), Seoul National University; Department of Neuropsychiatry (Y.M.C.), University of Ulsan College of Medicine, Ulsan University Hospital; Department of Psychiatry (J.-W.C.), Eulji General Hospital; Department of Neuropsychiatry (J.H.L., Y.J.L., D.Y.L.), Center for Sleep and Chronobiology (Y.J.L.), Seoul National University Hospital; and Health Service Group (S.H.H.), Samsung Electronics, Co., Ltd., Suwon, Republic of Korea.
Neurology. 2018 Mar 27;90(13):e1167-e1173. doi: 10.1212/WNL.0000000000005193. Epub 2018 Feb 28.
To clarify the relationships between sleep-wake cycle and cerebral β-amyloid (Aβ) deposition in cognitively normal (CN) older adults, focusing primarily on the moderating effects of the ε4 allele.
The present study included 133 CN older adults who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease cohort. All participants underwent [C] Pittsburgh compound B-PET imaging to quantify Aβ deposition in the brain and blood sampling for genotyping. Sleep and circadian parameters were measured using actigraphy for 8 consecutive days.
The ε4 allele had moderating effects on the associations of sleep latency (SL), mesor, and acrophase with cerebral Aβ deposition, and the interactions between ε4 status and SL and between ε4 status and acrophase remained significant after adjusting for multiple comparisons. In ε4 noncarriers, shorter SL, higher mesor, and advanced acrophase were associated with Aβ positivity. In contrast, ε4 carriers showed a relationship between delayed acrophase and Aβ accumulation that approached but did not reach significance. After the Bonferroni correction, the associations of shorter SL and higher mesor with Aβ positivity remained significant for ε4 noncarriers.
Our findings suggest that the ε4 allele may act as a moderator in the relationship between the sleep-wake cycle and Aβ accumulation in CN older adults. Thus, ε4 status needs to be considered as a key factor when designing related research or interventions.
阐明认知正常（CN）老年人睡眠-觉醒周期与脑β-淀粉样蛋白（Aβ）沉积之间的关系，主要关注 ε4 等位基因的调节作用。
本研究纳入了 133 名参加韩国脑老化研究早期诊断和预测阿尔茨海默病队列的 CN 老年人。所有参与者均接受了 [C]匹兹堡化合物 B-PET 成像，以定量脑内 Aβ沉积，并进行血液采样以进行基因分型。使用活动记录仪连续 8 天测量睡眠和昼夜节律参数。
ε4 等位基因对睡眠潜伏期（SL）、中值和峰值与脑内 Aβ沉积的关系具有调节作用，ε4 状态与 SL 和 ε4 状态与峰值之间的相互作用在进行多次比较调整后仍然显著。在 ε4 非携带者中，较短的 SL、较高的中值和提前的峰值与 Aβ 阳性相关。相比之下，ε4 携带者表现出与 Aβ 积累相关的延迟峰值，接近但未达到显著水平。在 Bonferroni 校正后，较短的 SL 和较高的中值与 Aβ 阳性的关联在 ε4 非携带者中仍然显著。
我们的研究结果表明，ε4 等位基因可能在 CN 老年人的睡眠-觉醒周期与 Aβ 积累之间的关系中起调节作用。因此，在设计相关研究或干预措施时，需要考虑 ε4 状态这一关键因素。
