Patients with Alzheimer disease (AD) frequently suffer from various sleep disturbances. However, how sleep disturbance is associated with AD and its progression remains poorly investigated. We investigated the association of total sleep time with brain amyloid and tau burden, cortical atrophy, cognitive dysfunction, and their longitudinal changes in the AD spectrum.

In this retrospective cohort study, we enrolled participants on the AD spectrum who were positive on ¹⁸F-florbetaben (FBB) PET. All participants underwent the Pittsburgh Sleep Quality Index, brain MRI, FBB PET, ¹⁸F-flortaucipir (FTP) PET, and detailed neuropsychological testing. In addition, a subset of participants completed follow-up assessments. We analyzed the association of total sleep time with the baseline and longitudinal FBB-standardized uptake value ratio (SUVR), FTP-SUVR, cortical thickness, and cognitive domain composite scores.

We examined 138 participants on the AD spectrum (15 with preclinical AD, 62 with prodromal AD, and 61 with AD dementia; mean age 73.4 ± 8.0 years; female 58.7%). Total sleep time was longer in the AD dementia group (7.4 ± 1.6 hours) compared with the preclinical (6.5 ± 1.4 hours; p = 0.026) and prodromal groups (6.6 ± 1.4 hours; p = 0.001), whereas other sleep parameters did not differ between groups. Longer total sleep time was not associated with amyloid accumulation but rather with tau accumulation, especially in the amygdala, hippocampus, basal forebrain, insular, cingulate, occipital, inferior temporal cortices, and precuneus. Longer total sleep time predicted faster tau accumulation in Braak regions V-VI (β = 0.016, p = 0.007) and disease progression to mild cognitive impairment or dementia (hazard ratio = 1.554, p = 0.024). Longer total sleep time was also associated with memory deficit (β = –0.19, p = 0.008).

Prolonged total sleep time was associated with tau accumulation in sleep-related cortical and subcortical areas as well as memory dysfunction. It also predicted faster disease progression with tau accumulation. Our study highlights the clinical importance of assessing total sleep time as a marker for disease severity and prognosis in the AD spectrum.

阿尔茨海默病（AD）患者经常遭受各种睡眠障碍的困扰。然而，睡眠障碍如何与 AD 及其进展相关的研究仍然很少。我们研究了总睡眠时间与大脑淀粉样蛋白和 tau 蛋白负荷、皮质萎缩、认知功能障碍及其在 AD 谱中的纵向变化之间的关系。

^{在这项回顾性队列研究中，我们招募了18} F-florbetaben (FBB) PET检测呈阳性的 AD 谱系参与者。所有参与者均接受了匹兹堡睡眠质量指数、脑部 MRI、FBB PET、¹⁸ F-flortaucipir (FTP) PET 和详细的神经心理学测试。此外，一部分参与者完成了后续评估。我们分析了总睡眠时间与基线和纵向 FBB 标准化摄取值比 (SUVR)、FTP-SUVR、皮质厚度和认知领域综合评分的关联。

我们检查了 138 名 AD 谱系参与者（15 名患有临床前 AD，62 名患有前驱期 AD，61 名患有 AD 痴呆；平均年龄 73.4 ± 8.0 岁；女性 58.7%）。与临床前组（6.5 ± 1.4 小时；p = 0.026）和前驱组（6.6 ± 1.4 小时；p = 0.001）相比，AD 痴呆组的总睡眠时间更长（7.4 ± 1.6 小时），而其他睡眠参数则没有变化。组之间存在差异。较长的总睡眠时间与淀粉样蛋白积累无关，而与 tau 蛋白积累相关，尤其是在杏仁核、海马、基底前脑、岛叶、扣带回、枕叶、颞下皮质和楔前叶。总睡眠时间较长可预测 Braak V-VI 区 tau 蛋白积累速度加快（β = 0.016，p = 0.007）以及疾病进展为轻度认知障碍或痴呆（风险比 = 1.554，p = 0.024）。较长的总睡眠时间也与记忆缺陷相关（β = –0.19，p = 0.008）。

总睡眠时间延长与睡眠相关皮质和皮质下区域的 tau 蛋白积累以及记忆功能障碍有关。它还预测随着 tau 蛋白积累，疾病进展会更快。我们的研究强调了评估总睡眠时间作为 AD 谱系疾病严重程度和预后标志的临床重要性。