Sleep in Huntington's disease gene expansion carriers: A systematic review

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by an abnormal CAG repeat expansion in the huntingtin gene, resulting in motor, cognitive, and psychiatric impairments. Sleep disturbances are a prevalent yet underexplored feature in both premanifest gene carriers and individuals with manifest disease. Given their potential as early disease markers and their significant impact on quality of life, understanding these sleep alterations is clinically critical. This systematic review synthesized findings from 78 studies, revealing a wide prevalence of sleep disturbances, ranging from 13% to 77%, reflecting methodological heterogeneity across studies. Subjective reports commonly cited poor sleep quality, insomnia, and excessive daytime sleepiness. These were confirmed by objective measures showing fragmented sleep, reduced efficiency, altered REM and slow-wave sleep, and disrupted circadian rhythms. Pathophysiological investigations suggest these issues are linked to hypothalamic dysfunction, altered neurotransmitter systems, and abnormal cortical synchronization. Clinically, sleep disturbances often precede motor symptom onset, suggesting their potential as prodromal indicators. Despite their impact, evidence for effective pharmacological or behavioral treatments remains scarce and inconclusive. Overall, sleep disruption in HD is a multifaceted phenomenon tied to disease progression, psychiatric symptoms, and neurodegeneration. Future research should prioritize longitudinal approaches that integrate objective sleep measures, neuroimaging, and genetic analyses to clarify causal mechanisms and guide targeted interventions to improve quality of life.