ImportanceSleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-β (Aβ) pathology. For effective AD prevention, it is essential to pinpoint the specific disturbances in sleep and the underlying 24-hour activity rhythms that confer the highest risk of Aβ deposition.ObjectiveTo determine the associations of 24-hour activity rhythms and sleep with Aβ deposition in adults without dementia, to evaluate whether disrupted 24-hour activity and sleep may precede Aβ deposition, and to assess the role of the apolipoprotein E ε4 (APOE4) genotype.Design, Setting, and ParticipantsThis was an observational cohort study using data from the Rotterdam Study. Of 639 participants without dementia who underwent Aβ positron emission tomography (PET) from September 2018 to November 2021, 319 were included in the current study. Exclusion criteria were no APOE genotyping and no valid actigraphy data at the baseline visits from 2004 to 2006 or from 2012 to 2014. The mean (SD) follow-up was 7.8 (2.4) years. Data were analyzed from March 2023 to April 2024.ExposuresActigraphy (7 days and nights, objective sleep, and 24-hour activity rhythms), sleep diaries (self-reported sleep), Aβ42/40, phosphorylated tau (p-tau)181 and p-tau217 plasma assays, 18F-florbetaben PET (mean standard uptake value ratio [SUVR] in a large cortical region of interest), and APOE4 genotype.Main Outcomes and MeasuresAssociation of objective and self-reported sleep and 24-hour activity rhythms at baseline with brain Aβ PET burden at follow-up.ResultsThe mean (range) age in the study population was 61.5 (48-80) years at baseline and 69.2 (60-88) years at follow-up; 150 (47%) were women. Higher intradaily variability at baseline, an indicator of fragmented 24-hour activity rhythms, was associated with higher Aβ PET burden at follow-up (β, 0.15; bootstrapped 95% CI, 0.04 to 0.26; bootstrapped P = .02, false discovery rate [FDR] P = .048). APOE genotype modified this association, which was stronger in APOE4 carriers (β, 0.38; bootstrapped 95% CI, 0.05 to 0.64; bootstrapped P = .03) compared to noncarriers (β, 0.07; bootstrapped 95% CI, −0.04 to 0.18; bootstrapped P = .19). The findings remained largely similar after excluding participants with AD pathology at baseline, suggesting that a fragmented 24-hour activity rhythm may have preceded Aβ deposition. No other objective or self-reported measure of sleep was associated with Aβ.Conclusions and RelevanceAmong community-dwelling adults included in this study, higher fragmentation of the 24-hour activity rhythms was associated with greater subsequent Aβ burden, especially in APOE4 carriers. These results suggest that rest-activity fragmentation could represent a modifiable risk factor for AD.

中文翻译：

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睡眠、24 小时活动节律和随后的 β 淀粉样蛋白病理学


重要性睡眠障碍在老年人中很常见，并且与阿尔茨海默病 (AD) 的发展有关，例如淀粉样蛋白 -β (Aβ) 病理学。为了有效预防 AD，必须查明睡眠中的特定干扰以及导致 Aβ 沉积风险最高的潜在 24 小时活动节律。目的确定成人中 24 小时活动节律和睡眠与 Aβ 沉积的关系。痴呆症，评估 24 小时活动和睡眠中断是否可能先于 Aβ 沉积，并评估载脂蛋白 E ε4 的作用（载脂蛋白4 ）基因型。设计、设置和参与者这是一项使用鹿特丹研究数据的观察性队列研究。在 2018 年 9 月至 2021 年 11 月期间接受 Aβ 正电子发射断层扫描 (PET) 的 639 名无痴呆症参与者中，有 319 人被纳入本研究。排除标准为无APOE基因分型，并且在 2004 年至 2006 年或 2012 年至 2014 年基线访视时没有有效的体动记录数据。平均 (SD) 随访时间为 7.8 (2.4) 年。数据分析时间为 2023 年 3 月至 2024 年 4 月。暴露活动记录仪（7 天 7 夜、客观睡眠和 24 小时活动节律）、睡眠日记（自我报告的睡眠）、Aβ42/40、磷酸化 tau (p-tau) 181和p-tau蛋白217血浆检测， 18 F-florbetaben PET（大感兴趣皮质区域的平均标准摄取值比 [SUVR]），以及载脂蛋白4基因型。主要结果和测量基线时客观和自我报告的睡眠和 24 小时活动节律与随访时脑 Aβ PET 负荷的关联。结果研究人群的平均（范围）年龄为 61.5（48-80）岁。基线和 69。2（60-88）年随访； 150 名（47%）是女性。基线日内较高变异性（碎片化 24 小时活动节律的指标）与随访时较高的 Aβ PET 负担相关（β，0.15；自举 95% CI，0.04 至 0.26；自举磷= .02，错误发现率 [FDR]磷=.048）。 APOE基因型改变了这种关联，这种关联在载脂蛋白4载体（β，0.38；自举 95% CI，0.05 至 0.64；自举磷= .03) 与非携带者相比 (β, 0.07; 自举 95% CI, −0.04 至 0.18; 自举磷=.19）。在排除基线时患有 AD 病理的参与者后，结果仍然基本相似，这表明支离破碎的 24 小时活动节律可能先于 Aβ 沉积。没有其他客观或自我报告的睡眠测量方法与 Aβ 相关。结论和相关性 在本研究纳入的社区居住成年人中，24 小时活动节律的高度碎片化与随后更大的 Aβ 负担相关，尤其是在载脂蛋白4载体。这些结果表明，休息活动碎片化可能代表 AD 的一个可改变的危险因素。