Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies.
Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies.
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DOI：
10.1093/sleepadvances/zpab015
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Rosenberg PB
中科院分区：
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作者：
Spira AP;Zipunnikov V;Raman R;Choi J;Di J;Bai J;Carlsson CM;Mintzer JE;Marshall GA;Porsteinsson AP;Yaari R;Wanigatunga SK;Kim J;Wu MN;Aisen PS;Sperling RA;Rosenberg PB
在β-淀粉样蛋白(Aβ)抗体临床试验筛选阶段的亚样本中检查睡眠障碍和24小时休息/活动节律(RAR)改变是否可作为临床前阿尔茨海默病(AD)的标志。总的来说，在无症状阿尔茨海默病(A4)的抗淀粉样蛋白治疗(A4)和淀粉样蛋白风险纵向评估和神经变性(LEAD)研究中，认知正常的26名Aβ阳性(Aβ+)和33名Aβ阴性(Aβ−)的参与者(平均年龄=71.3±4.6岁，女性占59%)分别佩戴活动记录仪5.66±0.8824小时。我们计算标准睡眠参数、标准RAR指标(节律、幅度、峰期、日间稳定性、日内变异性、相对幅度的平均估计统计量)，并执行新的RAR分析(标量函数回归[FOSR])。在我们的样本量下，我们无法检测到Aβ+和Aβ−参与者在标准睡眠参数或RAR指标上的任何差异。然而，当我们使用新的FOSR方法时，Aβ+参与者在深夜到清晨(晚上11：30到凌晨3：00)的活动水平低于Aβ−参与者，在清晨(凌晨4：30到8：30)和中午到下午晚些时候(12：30到5：30；均P<；0.05)。从晚上9：30到凌晨1：00和凌晨4：30到早上8：30，Aβ+参与者的活动也有较高的变异性，而从凌晨2：30到凌晨3：30的变异性较低(均为P<；0.05)。虽然我们没有发现临床前AD与标准的活动睡眠或RAR指标相关，但一种新的数据驱动的分析方法在临床前AD中发现了时间上的“局部”RAR改变。
To examine in a subsample at the screening phase of a clinical trial of a β-amyloid (Aβ) antibody whether disturbed sleep and altered 24-hour rest/activity rhythms (RARs) may serve as markers of preclinical Alzheimer’s disease (AD). Overall, 26 Aβ-positive (Aβ+) and 33 Aβ-negative (Aβ−) cognitively unimpaired participants (mean age = 71.3 ± 4.6 years, 59% women) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, respectively, wore actigraphs for 5.66 ± 0.88 24-hour periods. We computed standard sleep parameters, standard RAR metrics (mean estimating statistic of rhythm, amplitude, acrophase, interdaily stability, intradaily variability, relative amplitude), and performed a novel RAR analysis (function-on-scalar regression [FOSR]). We were unable to detect any differences between Aβ+ and Aβ− participants in standard sleep parameters or RAR metrics with our sample size. When we used novel FOSR methods, however, Aβ+ participants had lower activity levels than Aβ− participants in the late night through early morning (11:30 pm to 3:00 am), and higher levels in the early morning (4:30 am to 8:30 am) and from midday through late afternoon (12:30 pm to 5:30 pm; all p < .05). Aβ+ participants also had higher variability in activity across days from 9:30 pm to 1:00 am and 4:30 am to 8:30 am, and lower variability from 2:30 am to 3:30 am (all p < .05). Although we found no association of preclinical AD with standard actigraphic sleep or RAR metrics, a novel data-driven analytic method identified temporally “local” RAR alterations in preclinical AD.