Sleep Disturbances in Huntington’s Disease: Impact on Disease Outcomes
A good night’s sleep is critical for overall well-being and health. However, for individuals with Huntington’s disease (HD), sleep disturbances present an additional burden that can worsen disease outcomes and affect their quality of life. The Journal of Huntington’s Disease (JHD) has dedicated a special issue to explore the current knowledge and gaps in understanding sleep and circadian rhythms in HD.
Sleep disruptions can have detrimental effects on metabolism and increase vulnerability to infections. Many of us have experienced the negative impact of a night of poor sleep, such as irritability, slow thinking, and physical exhaustion. We often assume that these effects are temporary and will have no lasting consequences. However, emerging research suggests that sleep and circadian rhythm abnormalities are associated with neurodegenerative diseases.
Guest Editor of the special issue, Jenny Morton, PhD, ScD, Professor of Neurobiology at the University of Cambridge, emphasizes the importance of healthy sleep and diurnal rhythms for human health. She acknowledges that while we tend to overlook their significance, it becomes a focal point when they become disrupted. In the case of HD, the critical question is whether chronically disturbed sleep and circadian rhythms, which are already detrimental to neurologically normal individuals, have an even greater impact on individuals whose brains are vulnerable due to HD.
The relationship between sleep disorders and HD pathogenesis remains unclear. It is uncertain whether sleep disorders precede the development of the disease or if they solely manifest as debilitating symptoms of the underlying changes. However, the contributing authors to this special issue argue that sleep disturbances contribute to an additional burden in HD patients, potentially exacerbating the progression of the disease.
The special issue highlights that sleep and circadian dysfunction in HD patients have been understudied and neglected. The lack of recognition of this problem hampers progress in the field. Sleep dysfunction is taken seriously in the general population, as it exacerbates cognitive symptoms and affects executive function, memory consolidation, attention, processing speed, impulsivity, and emotional stability. These symptoms are also present in HD, but the impact of sleep dysfunction on HD patients is rarely considered.
There is growing evidence from clinical and animal model studies suggesting that sleep changes occur early in the clinical course of HD. Sleep initiation and maintenance difficulties lead to decreased sleep efficiency and progressive deterioration of sleep architecture. However, these sleep alterations are often underreported by patients and underrecognized by healthcare professionals.
Treating sleep and circadian disturbances in HD is a significant unmet need. The special issue recommends well-designed intervention studies to address poor sleep associated with HD. Noninvasive and cost-effective circadian-based therapies like light therapy show promise in managing sleep-wake disturbances in HD patients.
HD is a hereditary neurodegenerative condition characterized by motor, cognitive, and psychiatric features resulting from a mutation in the huntingtin gene. Current treatment approaches aim to manage symptoms, as there is no treatment that slows or halts the progression of the disease. However, these approaches do not consider the impact of commonly used medications on sleep or directly address sleep dysfunction.
The review article in the special issue discusses the impacts of current medications and prospects for treating sleep dysfunction in HD. It evaluates literature from clinical studies in HD, other neurodegenerative conditions, and preclinical models of HD to explore potential approaches in these areas.
Sleep disruption not only exacerbates cognitive and affective symptoms but can also directly affect neurodegenerative processes by inducing neuroinflammation or impairing glymphatic clearance of neurotoxic waste during slow-wave sleep. If sleep deprivation is associated with an increase in neurotoxic proteins like amyloid and tau, which contribute to neurodegeneration in Alzheimer’s disease, it may also affect the HD brain. This connection is particularly relevant considering recent links between tau and HD disease progression.
Senior author Prof. Roger A. Barker highlights the potential of addressing sleep pathology in HD as a treatment approach that could alleviate motor, cognitive, and psychiatric symptoms, and potentially modify disease progression. Sleep interventions in preclinical models of HD have shown improved behavioral and survival outcomes, suggesting the significance of sleep in HD management.
The Journal of Huntington’s Disease praises the special issue for shedding light on the underappreciated role of sleep and circadian disorders in HD. Recognizing and addressing sleep dysfunction is crucial for improving the quality of life for individuals with HD. However, more research and awareness are needed in this field to effectively manage this aspect of the disease.
In conclusion, good quality sleep and healthy circadian rhythms play a fundamental role in human health, and disruptions can have severe consequences. The special issue on sleep in HD highlights the need for a better understanding of sleep disturbances in HD patients and emphasizes the importance of recognizing and treating sleep dysfunction to alleviate symptoms and potentially modify disease progression.
