Sleep monitoring may provide markers for future Alzheimer’s disease; however, the relationship between sleep and cognitive function in preclinical and early symptomatic Alzheimer’s disease is not well understood. Multiple studies have associated short and long sleep times with future cognitive impairment. Since sleep and the risk of Alzheimer’s disease change with age, a greater understanding of how the relationship between sleep and cognition changes over time is needed. In this study, we hypothesized that longitudinal changes in cognitive function will have a non-linear relationship with total sleep time, time spent in non-REM and REM sleep, sleep efficiency and non-REM slow wave activity. To test this hypothesis, we monitored sleep-wake activity over 4–6 nights in 100 participants who underwent standardized cognitive testing longitudinally, APOE genotyping, and measurement of Alzheimer’s disease biomarkers, total tau and amyloid-β42 in the CSF. To assess cognitive function, individuals completed a neuropsychological testing battery at each clinical visit that included the Free and Cued Selective Reminding test, the Logical Memory Delayed Recall assessment, the Digit Symbol Substitution test and the Mini-Mental State Examination. Performance on each of these four tests was Z-scored within the cohort and averaged to calculate a preclinical Alzheimer cognitive composite score. We estimated the effect of cross-sectional sleep parameters on longitudinal cognitive performance using generalized additive mixed effects models. Generalized additive models allow for non-parametric and non-linear model fitting and are simply generalized linear mixed effects models; however, the linear predictors are not constant values but rather a sum of spline fits. We found that longitudinal changes in cognitive function measured by the cognitive composite decreased at low and high values of total sleep time (P < 0.001), time in non-REM (P < 0.001) and REM sleep (P < 0.001), sleep efficiency (P < 0.01) and <1 Hz and 1–4.5 Hz non-REM slow wave activity (P < 0.001) even after adjusting for age, CSF total tau/amyloid-β42 ratio, APOE ε4 carrier status, years of education and sex. Cognitive function was stable over time within a middle range of total sleep time, time in non-REM and REM sleep and <1 Hz slow wave activity, suggesting that certain levels of sleep are important for maintaining cognitive function. Although longitudinal and interventional studies are needed, diagnosing and treating sleep disturbances to optimize sleep time and slow wave activity may have a stabilizing effect on cognition in preclinical or early symptomatic Alzheimer’s disease.

中文翻译：

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临床前和早期症状性阿尔茨海默病的睡眠和纵向认知表现

睡眠监测可能为未来的阿尔茨海默病提供标志物；然而，临床前和早期症状性阿尔茨海默病的睡眠与认知功能之间的关系尚不清楚。多项研究表明睡眠时间的长短与未来的认知障碍有关。由于睡眠和阿尔茨海默病的风险随着年龄的增长而变化，因此需要更好地了解睡眠和认知之间的关系如何随着时间的推移而变化。在这项研究中，我们假设认知功能的纵向变化与总睡眠时间、非快速眼动和快速眼动睡眠时间、睡眠效率和非快速眼动慢波活动存在非线性关系。为了检验这一假设，我们监测了 100 名参与者 4-6 个晚上的睡眠-觉醒活动，这些参与者接受了纵向标准化认知测试、APOE 基因分型以及阿尔茨海默病生物标志物、脑脊液中总 tau 蛋白和淀粉样蛋白-β42 的测量。为了评估认知功能，个人在每次临床就诊时完成了一套神经心理学测试，包括自由和提示选择性提醒测试、逻辑记忆延迟回忆评估、数字符号替换测试和简易精神状态检查。这四项测试中每一项的表现均在队列内进行 Z 评分，并取平均值以计算临床前阿尔茨海默氏症认知综合评分。我们使用广义加性混合效应模型估计了横截面睡眠参数对纵向认知表现的影响。广义加性模型允许非参数和非线性模型拟合，并且是简单的广义线性混合效应模型；然而，线性预测变量不是常数值，而是样条拟合的总和。我们发现，认知综合测量的认知功能纵向变化在总睡眠时间（P < 0.001）、非快速眼动睡眠时间（P < 0.001）和快速眼动睡眠时间（P < 0.001）的低值和高值时减少。 、睡眠效率 (P < 0.01) 和 <1 Hz 和 1–4.5 Hz 非快速眼动慢波活动 (P < 0.001)，即使在调整年龄、CSF 总 tau/淀粉样蛋白-β42 比率、APOE ε4 携带者状态后、受教育年限和性行为。认知功能随着时间的推移在总睡眠时间、非快速眼动睡眠和快速眼动睡眠时间以及＜1Hz慢波活动的中间范围内保持稳定，这表明一定水平的睡眠对于维持认知功能是重要的。尽管需要纵向和介入研究，但诊断和治疗睡眠障碍以优化睡眠时间和慢波活动可能对临床前或早期症状性阿尔茨海默病的认知产生稳定作用。