The Treatment of Sleep Dysfunction in Neurodegenerative Disorders
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REVIEW
The Treatment of Sleep Dysfunction in Neurodegenerative Disorders Zanna J. Voysey 1 & Roger A. Barker 2 & Alpar S. Lazar 3 Accepted: 22 October 2020 # The Author(s) 2020Abstract
Sleep dysfunction is highly prevalent across the spectrum of neurodegenerative conditions and is a key determinant of quality of life for both patients and their families. Mounting recent evidence also suggests that such dysfunction exacerbates cognitive and affective clinical features of neurodegeneration, as well as disease progression through acceleration of pathogenic processes. Effective assessment and treatment of sleep dysfunction in neurodegeneration is therefore of paramount importance; yet robust therapeutic guidelines are lacking, owing in part to a historical paucity of effective treatments and trials. Here, we review the common sleep abnormalities evident in neurodegenerative disease states and evaluate the latest evidence for traditional and emerging interventions, both pharmacological and nonpharmacological. Interventions considered include conservative measures, targeted treatments of specific clinical sleep pathologies, established sedating and alerting agents, melatonin, and orexin antagonists, as well as bright light therapy, behavioral measures, and slow-wave sleep augmentation techniques. We conclude by providing a suggested framework for treatment based on contemporary evidence and highlight areas that may emerge as major therapeutic advances in the near future. Key Words Sleep . Insomnia . Neurodegeneration . Dementia . Alzheimer’s . Parkinson’s
Introduction Sleep dysfunction is prominent across the spectrum of neurodegenerative conditions, occurring in 40 to 0% of patients [1–5]. It is a key determinant of patients’ quality of life [6], falls risk [7], and progression to institutionalization [8–11], as well as caregiver burden and health [12–14]. It should therefore be a priority in the clinical care of patients with neurodegenerative disease but is currently typically overlooked. Moreover, mounting recent evidence contends that sleep dysfunction contributes to the severity and progression of neurodegeneration [15]. On a symptomatic level, it is wellestablished that sleep deprivation and disruption leads to deficits in attention, executive function, and processing speed, as
* Alpar S. Lazar [email protected] 1
Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UK
2
Department of Clinical Neurosciences, John van Geest Centre for Brain Repair and WT-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0PY, UK
3
Faculty of Medicine and Health Sciences, University of East Anglia, Norwich NR4 7TJ, UK
well as promoting impulsivity, emotional lability, and depression [16–20]. Sleep abnormalities therefore almost certainly contribute to the burden of such features common to neurodegenerative conditions. Importantly, however, exacerbation may also occur at the level of the underlying pathogenic processes. The discovery
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