[Sleep abnormality as a potential target of disease-modifying therapy for neurodegenerative diseases]

Sleep abnormality such as frequent nocturnal arousal and decreased deep non-REM (rapid-eye-movement) sleep is a prevalent but under-recognized symptom that affects patients with various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). In contrast to the conventional understanding that the sleep abnormality in these patients is caused by AD or PD pathology in the brain regions regulating sleep-wake or circadian rhythm, various epidemiological studies have demonstrated the association of sleep abnormality with an increased risk of these diseases. Through various recent studies using relevant animal models to test the causal relationship between sleep abnormality and neurodegenerative diseases, the recent concept of a bidirectional relationship between sleep abnormality and neurodegenerative diseases was established. However, whether therapeutic interventions against sleep abnormality would modify the disease course of neurodegenerative diseases remains unknown. In this review, we will first provide an overview of previous studies that link neurodegenerative diseases and sleep abnormality, mainly focusing on the sleep abnormality in patients with AD. We will then introduce the studies that examined the causal relationship between sleep abnormality and neurodegenerative diseases. Finally, we will discuss possible mechanisms underlying the bidirectional relationship between sleep abnormality and neurodegenerative diseases. A better understanding of these mechanisms would lead to the development of novel pharmacological and/or non-pharmacological treatments that would modify the disease course of neurodegenerative diseases through targeting the processes related to sleep abnormality in the patients of neurodegenerative diseases.