1. 睡眠紊乱是AD早期的特征性表现；

1.1 携带APOEe4等位基因的高风险罹患AD健康老年人存在睡眠功能紊乱；

Evidence of association between sleep quality and APOE ε4 in healthy older adults: A pilot study.

Examining the association between Apolipoprotein E (APOE) and self-reported sleep disturbances in non-demented older adults.

1.2 AD睡眠紊乱可能早期影响脑干的结构；

Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects withAlzheimer's disease.

1.3 慢波睡眠减少和健康老年人脑脊液Aβ水平升高相关；

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly.

1.4 中老年人早期睡眠质量和脑容量、脑代谢和Aβ沉积相关；

Relationships between sleep quality and brain volume, metabolism, and amyloid deposition in late adulthood.

1.5 AD和遗忘型轻度认知功能障碍存在顶叶快速睡眠波密度下降；

Parietal Fast Sleep Spindle Density Decrease in Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

1.6 伴有行为和精神异常的早期AD患者存在睡眠障碍；

Sleep disturbances are key symptoms of very early stage Alzheimer disease with behavioral and psychological symptoms: a Japan multi-center cross-sectional study (J-BIRD).

1.7 促觉醒因子Orexin和健康老年人脑脊液中的p-tau水平相关；

Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects.

1.8 老年人睡眠不佳和记忆力下降有关；

Subjective memory complaints in an elderly population with poor sleep quality.

1.9 睡眠片断化可能影响大脑皮层结构；

Regional Neocortical Gray Matter Structure and Sleep Fragmentation in Older Adults.

1.10 REM睡眠脑电波异常和不稳定是轻度认知功能障碍的特征。

Quantitative EEG of Rapid-Eye-Movement Sleep: A Marker of Amnestic Mild Cognitive Impairment.

Non-rapid eye movement sleep instability in mild cognitive impairment: a pilot study.

1.11 睡眠不足是痴呆的危险因子。

Daytime Sleepiness and Sleep Inadequacy as Risk Factors for Dementia.

2. 睡眠紊乱加重AD的神经病理学改变；

2.1 睡眠紊乱可以促进毒性蛋白Aβ的产生；

Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk ofAlzheimer Disease.

Frontal cortical mitochondrial dysfunction and mitochondria-related β-amyloid accumulation by chronic sleep restriction in mice.

The Relationship between Sleep Quality and Brain Amyloid Burden.

Candidate mechanisms underlying the association between sleep-wake disruptions andAlzheimer's disease.

Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice.

2.2 睡眠紊乱可以促进tau蛋白磷酸化；

Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice.

Increased cerebrospinal fluid levels of nerve cell biomarkers in narcolepsy with cataplexy.

Beta-amyloid and phosphorylated tau metabolism changes in narcolepsy over time.

2.3 睡眠紊乱可以促进神经元结构异常和功能障碍；

Chronic sleep disturbance and neural injury: links to neurodegenerative disease.

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1.

Rapid Eye Movement Sleep Deprivation Induces Neuronal Apoptosis by Noradrenaline Acting on Alpha1 Adrenoceptor and by Triggering Mitochondrial Intrinsic Pathway.

Sleep deprivation and hippocampal vulnerability: changes in neuronal plasticity, neurogenesis and cognitive function.

2.4 睡眠紊乱可以通过影响Orexin系统进而促进AD的发生；

Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer's disease.

Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer's disease.

Alzheimer disease: increased orexin level correlates with sleep disruption and cognitive decline inAlzheimer disease.

Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease.

2.5 Aβ可以加重睡眠紊乱。

Exploring the bi-directional relationship between sleep and beta-amyloid.

Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila.

Sleep interacts with aβ to modulate intrinsic neuronal excitability.

3. 睡眠紊乱加重AD的认知功能障碍；

3.1 睡眠紊乱可以通过促进Aβ毒性蛋白沉积进而损害认知功能；

The interaction of sleep and amyloid deposition on cognitive performance.

Mechanisms linking circadian clocks, sleep, and neurodegeneration.

Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.

3.2. 研究证明AD睡眠障碍和认知功能损害相关；

Sleep, Cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis.

Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease

Alzheimer disease: increased orexin level correlates with sleep disruption and cognitive decline inAlzheimer disease.

Impact of sleep on the risk of cognitive decline and dementia.

4. 改善睡眠有助于促进AD的预防和治疗；

4.1 褪黑素可能有助于治疗AD；

Meta-analysis of randomized, double-blind, placebo-controlled trials of melatonin in Alzheimer's disease.

Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases.

The effect of memantine on sleep architecture and psychiatric symptoms in patients withAlzheimer's disease.

Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials.

4.2 痴呆中的睡眠障碍治疗有助于改善AD生活质量；

Treatment of Sleep Disorders in Dementia.

Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology ofAlzheimer's Disease?

Pharmacotherpy and Alzheimer's Disease: The M-Drugs (Melatonin, Minocycline, Modafinil, and Memantine) Approach.

Clinical management of sleep disturbances in Alzheimer's disease: current and emerging strategies.

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