Zihui Wang1,2  · Feifei He3  · Lingzhi Li1  · Wei Wang1  · Lisan Zhang1  · Jinsong Tang2  · Weidong Le1,3

1 Department of Neurology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310000, China 

2 Department of Psychiatry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China 

3 Key Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian 116000, China

Abstract

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), and others, represent an escalating public health burden in aging populations. NDDs are characterized by progressive neuronal loss and misfolded protein aggregation. Despite distinct clinical heterogeneity, these diseases universally present with debilitating non-motor symptoms, among which sleep-wake disorders are highly prevalent. Once considered secondary to neuronal damage, growing evidence now highlights a bidirectional interplay: sleep disruption is not only a consequence of neurodegeneration but also exacerbates its progression. This review synthesizes this complex interplay, outlining sleep phenotypes across major NDDs, dissecting key underlying mechanisms (impaired protein homeostasis, glymphatic dysfunction, chronic neuroinflammation, sleep-regulatory nucleus vulnerability, and circadian dysregulation), and summarizing current pharmacotherapeutic and non-pharmacological interventions. Attenuating sleep disorders may therefore provide symptomatic relief and disease‑modifying effects for NDDs.

Keywords

Neurodegenerative diseases; Sleep disorders; Glymphatic system; REM sleep behavior disorder; Neuroinflammation

[SpringerLink]