Circadian disturbances in Alzheimer's disease progression: a prospective observational cohort study of community-based older adults.
Circadian disturbances in Alzheimer's disease progression: a prospective observational cohort study of community-based older adults.
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DOI：
10.1016/s2666-7568(20)30015-5
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Hu K
中科院分区：
文献类型：
--
作者：
Li P;Gao L;Gaba A;Yu L;Cui L;Fan W;Lim ASP;Bennett DA;Buchman AS;Hu K
昼夜节律紊乱在阿尔茨海默病患者中很常见，并且在没有痴呆症状但患有阿尔茨海默病病理的个体中也有报道。我们的目的是评估昼夜节律紊乱和阿尔茨海默病进展之间的时间关系。我们对1401名健康老年人（年龄>59岁）进行了一项前瞻性队列研究，这些人参加了拉什记忆和衰老项目（拉什大学医学中心，芝加哥，IL，美国），随访时间长达15年。参与者每年接受一次认知评估（21项认知性能测试）和运动活动（活动记录）。从腕动记录仪中提取四项措施来量化每日和昼夜节律，即24小时活动节律的振幅、峰值（代表活动时间）、24小时活动节律的日间稳定性和活动节律每小时碎片的日内变异性。我们使用考克斯比例风险模型和逻辑回归来评估昼夜节律紊乱是否预示着阿尔茨海默氏痴呆事件的风险增加以及轻度认知障碍向阿尔茨海默氏痴呆的转化。我们使用线性混合效应模型来研究昼夜节律如何纵向变化以及这种变化如何与阿尔茨海默氏症的进展相结合。参与者的中位年龄为81.8（IQR 76.3 - 85.7）岁。发生阿尔茨海默氏痴呆的风险随着幅度降低（1 SD降低，风险比[HR] 1.39，95%CI 1.19 - 1.62）和日内变异性升高（1 SD增加，1.22，1.04 - 1.43）而增加。在轻度认知障碍的参与者中，阿尔茨海默氏痴呆的风险增加是通过较低的振幅（1 SD降低，HR 1.46，95% CI 1.24 - 1.72），较高的日内变异性（1 SD增加，1.36，1.15 - 1.60）和较低的日间稳定性（1 SD降低，1.21，1.02 - 1.44）预测的。轻度认知障碍参与者更快转变为阿尔茨海默氏痴呆的预测依据是较低的振幅（1 SD降低，比值比[OR] 2.08，95%CI 1.53 - 2.93），增加的日内变异性（1 SD增加，1.97，1.43 - 2.79）和降低的日间稳定性（1 SD降低，1.35，1.01 - 1.84）。昼夜节律振幅、顶相和日间稳定性随时间逐渐降低，日内变异性随时间逐渐增加。阿尔茨海默氏症的进展加速了这些衰老效应，在诊断为轻度认知障碍后，这些指标的年变化增加了一倍或两倍以上，在诊断为阿尔茨海默氏症痴呆后，这些指标的年变化进一步增加了一倍。整体认知的纵向变化与振幅和日间稳定性的纵向变化呈正相关，与日内变异性的纵向变化呈负相关。我们的研究结果表明，昼夜节律失调和阿尔茨海默氏症的进展之间的联系，这意味着一个双向的关系或共享共同的潜在的病理生理机制。美国国立卫生研究院，和美国国家重点基金会。
Circadian disturbances are commonly seen in people with Alzheimer’s disease and have been reported in individuals without symptoms of dementia but with Alzheimer’s pathology. We aimed to assess the temporal relationship between circadian disturbances and Alzheimer’s progression. We did a prospective cohort study of 1401 healthy older adults (aged >59 years) enrolled in the Rush Memory and Aging Project (Rush University Medical Center, Chicago, IL, USA) who had been followed up for up to 15 years. Participants underwent annual assessments of cognition (with a battery of 21 cognitive performance tests) and motor activities (with actigraphy). Four measures were extracted from actigraphy to quantify daily and circadian rhythmicity, which were amplitude of 24-h activity rhythm, acrophase (representing peak activity time), interdaily stability of 24-h activity rhythm, and intradaily variability for hourly fragmentation of activity rhythm. We used Cox proportional hazards models and logistic regressions to assess whether circadian disturbances predict an increased risk of incident Alzheimer’s dementia and conversion of mild cognitive impairment to Alzheimer’s dementia. We used linear mixed-effects models to investigate how circadian rhythms changed longitudinally and how the change integrated to Alzheimer’s progression. Participants had a median age of 81·8 (IQR 76·3–85·7) years. Risk of developing Alzheimer’s dementia was increased with lower amplitude (1 SD decrease, hazard ratio [HR] 1·39, 95% CI 1·19–1·62) and higher intradaily variability (1 SD increase, 1·22, 1·04–1·43). In participants with mild cognitive impairment, increased risk of Alzheimer’s dementia was predicted by lower amplitude (1 SD decrease, HR 1·46, 95% CI 1·24–1·72), higher intradaily variability (1 SD increase, 1·36, 1·15–1·60), and lower interdaily stability (1 SD decrease, 1·21, 1·02–1·44). A faster transition to Alzheimer’s dementia in participants with mild cognitive impairment was predicted by lower amplitude (1 SD decrease, odds ratio [OR] 2·08, 95% CI 1·53–2·93), increased intradaily variability (1 SD increase, 1·97, 1·43–2·79), and decreased interdaily stability (1 SD decrease, 1·35, 1·01–1·84). Circadian amplitude, acrophase, and interdaily stability progressively decreased over time, and intradaily variability progressively increased over time. Alzheimer’s progression accelerated these aging effects by doubling or more than doubling the annual changes in these measures after the diagnosis of mild cognitive impairment, and further doubled them after the diagnosis of Alzheimer’s dementia. The longitudinal change of global cognition positively correlated with the longitudinal changes in amplitude and interdaily stability and negatively correlated with the longitudinal change in intradaily variability. Our results indicate a link between circadian dysregulation and Alzheimer’s progression, implying either a bidirectional relation or shared common underlying pathophysiological mechanisms. National Institutes of Health, and the BrightFocus Foundation.
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影响因子：
2.8
作者：
Mitchell JA;Quante M;Godbole S;James P;Hipp JA;Marinac CR;Mariani S;Cespedes Feliciano EM;Glanz K;Laden F;Wang R;Weng J;Redline S;Kerr J
通讯作者：
Kerr J
影响因子：
11.2
作者：
Tranah, Gregory J.;Blackwell, Terri;Stone, Katie L.;Ancoli-Israel, Sonia;Paudel, Misti L.;Ensrud, Kristine E.;Cauley, Jane A.;Redline, Susan;Hillier, Teresa A.;Cummings, Steven R.;Yaffe, Kristine
通讯作者：
Yaffe, Kristine
影响因子：
11.2
作者：
Bennett, David A.;Wilson, Robert S.;Boyle, Patricia A.;Buchman, Aron S.;Schneider, Julie A.
通讯作者：
Schneider, Julie A.
影响因子：
2.8
作者：
Luik, Annemarie I.;Zuurbier, Lisette A.;Tiemeier, Henning
通讯作者：
Tiemeier, Henning
影响因子：
9.9
作者：
Wilson, RS;Barnes, LL;Bennett, DA
通讯作者：
Bennett, DA