Fine-mapping the contribution of sleep alterations to neurodegeneration – a prospective polysomnographic study in the general population

痴呆是由可改变的和不可改变的因素之间的复杂相互作用引起的神经退行性疾病。其中，睡眠最近得到了关注，一项研究估计，高达15%的阿尔茨海默病病例可以通过有效的睡眠障碍治疗来推迟或预防。在最初的项目中，我们发现阻塞性睡眠呼吸暂停与晚期脑老化和白质高强度负荷之间以及慢波睡眠和阿尔茨海默病相关的脑萎缩模式之间存在强烈的关联。但是，尽管这些结果与假设的病理生理途径相一致，但对其他已发表的结果仍存在一些争议。这可能表明，对睡眠宏观结构和阻塞性睡眠呼吸暂停所用指标的分类和/或时间压缩可能不能准确地反映相关的睡眠过程。因此，利用波美拉尼亚健康研究(SHIP-TREND-0/1)普通人群研究的横断面和纵向多导睡眠图和结构MRI数据，我们建议将我们的分析扩展到基于EEG的微结构事件，结合时间和个人特定睡眠动态的全球睡眠标记，以及评估这些事件的时间和结构组成的低氧标记。我们相信，这些标记物将澄清一些争议，并为睡眠和阻塞性睡眠呼吸暂停对痴呆症相关神经变性的影响提供更多的洞察力。

Dementias are neurodegenerative disorders caused by a complex interaction between modifiable and non-modifiable factors. Among these, sleep has been recently gaining attention, with a study estimating that up to 15% of Alzheimer cases could be delayed or prevented through the effective treatment of sleep disorders. In the initial project, we found strong associations between obstructive sleep apnoea and advanced brain ageing and white matter hyperintensity burden, as well as between slow-wave sleep and Alzheimer-related brain atrophy patterns. But while these results are compatible with hypothesized pathophysiological pathways, some controversy remains regarding other published results. This might indicate that the categorization and/or temporal compression of the used metrics of sleep macro-architecture and obstructive sleep apnoea might not accurately reflect the relevant sleep processes. Using cross-sectional and longitudinal polysomnography and structural MRI data from the Study of Health in Pomerania (SHIP-Trend-0/1) general population study, we therefore propose to extend our analyses to EEG-based microstructural events, global sleep markers incorporating temporal and individual-specific dynamics of sleep and hypoxic markers assessing the temporal and structural composition of these events. We believe that these markers will clarify some of the controversy and provide additional insight into the impact of sleep and obstructive sleep apnoea on dementia-related neurodegeneration.