Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging.

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2021-10-01 DOI:10.1001/jamaneurol.2021.2876

Joseph R Winer, Kacie D Deters, Gabriel Kennedy, Meghan Jin, Andrea Goldstein-Piekarski, Kathleen L Poston, Elizabeth C Mormino

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引用次数: 70

Abstract

Importance: Disrupted sleep is common in aging and is associated with cognition. Age-related changes to sleep are associated with multiple causes, including early Alzheimer disease pathology (amyloid β [Aβ]), depression, and cardiovascular disease.

Objective: To investigate the associations between self-reported sleep duration and brain Aβ burden as well as the demographic, cognitive, and lifestyle variables in adults with normal cognition.

Design, setting, and participants: This cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, which is being conducted in 67 sites in the United States, Canada, Australia, and Japan. The sample for this analysis consisted of individuals aged 65 to 85 years who underwent an Aβ positron emission tomography (PET) scan, had complete apolipoprotein E (APOE) genotype data, and were identified as clinically normal (per a Clinical Dementia Rating score of 0) and cognitively unimpaired (per a Mini-Mental State Examination score of 25 to 30 and Logical Memory Delayed Recall test score of 6 to 18). Data were analyzed from April 3, 2020, to June 20, 2021.

Main outcomes and measures: The outcome was self-reported nightly sleep duration (grouped by short sleep duration: ≤6 hours, normal sleep duration: 7-8 hours, and long sleep duration: ≥9 hours) compared with demographic characteristics, Aβ burden (as measured with a fluorine 18-labeled-florbetapir PET scan), objective and subjective cognitive function measures, and lifestyle variables.

Results: The 4417 participants in the study included 2618 women (59%) and had a mean (SD) age of 71.3 (4.7) years. Self-reported shorter sleep duration was linearly associated with higher Aβ burden (β [SE] = -0.01 [0.00]; P = .005), and short sleep duration was associated with reduced cognition that was mostly in memory domains. No difference in Aβ was found between long and normal sleep duration groups (β [SE] = 0.00 [0.01]; P = .99). However, compared with normal sleep duration, both short and long sleep durations were associated with higher body mass index (short vs normal sleep duration: β [SE] = 0.48 [0.17], P = .01; long vs normal sleep duration: β [SE] = 0.97 [0.31], P = .002), depressive symptoms (short vs normal sleep duration: β [SE] = 0.31 [0.05], P < .001; long vs normal sleep duration: β [SE] = 0.39 [0.09], P < .001), and daytime napping (short vs normal sleep duration: β [SE] = 2.66 [0.77], P = .001; long vs normal sleep duration: β [SE] = 3.62 [1.38], P = .01). Long sleep duration was associated with worse performance across multiple cognitive domains.

Conclusions and relevance: In this cross-sectional study, both short and long sleep durations were associated with worse outcomes for older adults, such as greater Aβ burden, greater depressive symptoms, higher body mass index, and cognitive decline, emphasizing the importance of maintaining adequate sleep.

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睡眠时间长短与衰老过程中β淀粉样蛋白负荷和认知的关系

重要性:睡眠中断在衰老中很常见，并且与认知有关。与年龄相关的睡眠变化与多种原因有关，包括早期阿尔茨海默病病理(β淀粉样蛋白[Aβ])、抑郁症和心血管疾病。目的:探讨认知正常的成人自述睡眠时间与脑β负荷以及人口学、认知和生活方式变量之间的关系。设计、环境和参与者:这项横断面研究获得了无症状阿尔茨海默病抗淀粉样蛋白治疗(A4)研究参与者的数据，该研究正在美国、加拿大、澳大利亚和日本的67个地点进行。本分析的样本包括年龄在65至85岁之间的个体，他们接受了a β正电子发射断层扫描(PET)扫描，具有完整的载脂蛋白E (APOE)基因型数据，并且被确定为临床正常(按照临床痴呆评分为0分)和认知未受损(按照迷你精神状态检查得分为25至30分，逻辑记忆延迟回忆测试得分为6至18分)。数据分析时间为2020年4月3日至2021年6月20日。主要结局和测量:结果是自我报告的夜间睡眠时间(按短睡眠时间分组:≤6小时，正常睡眠时间:7-8小时，长睡眠时间:≥9小时)与人口学特征、a β负担(用氟- 18标记的florbetapir PET扫描测量)、客观和主观认知功能测量以及生活方式变量进行比较。结果:4417名参与者中包括2618名女性(59%)，平均(SD)年龄为71.3(4.7)岁。自我报告的较短睡眠时间与较高的Aβ负担呈线性相关(β [SE] = -0.01 [0.00];P = 0.005)，睡眠时间短与认知能力下降有关，这种下降主要发生在记忆领域。长睡眠时间组与正常睡眠时间组Aβ水平无显著差异(β [SE] = 0.00 [0.01];p = .99)。然而，与正常睡眠时间相比，短睡眠时间和长睡眠时间均与较高的体重指数相关(短睡眠时间与正常睡眠时间:β [SE] = 0.48 [0.17]， P = 0.01;结论和相关性:在这项横断面研究中，短睡眠时间和长睡眠时间与老年人较差的结局相关，如更大的Aβ负担、更大的抑郁症状、更高的体重指数和认知能力下降，强调了保持充足睡眠的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.