Sleep Fragmentation, 24-hr Rest-Activity Patterns, and Cognitive Function in Premanifest Huntington's Disease: An Actigraphy Study

Objective: In Huntington's disease (HD), cognitive symptoms, sleep fragmentation, and daily activity pattern alterations can occur up to 15 years before diagnosis in premanifest HD (Pre-HD). Whether sleep and rest-activity patterns relate to cognitive function in Pre-HD, however, remains unclear. We investigated the relationships between rest-activity patterns, sleep, and cognitive function in Pre-HD compared to healthy controls (HCs). Method: All participants completed 14 days of actigraphy, online questionnaires, and remote cognitive assessments. Results: The Pre-HD group (n = 36) performed worse on Speeded Tapping than the HC group (n = 42). Pre-HD participants with heightened sleep fragmentation performed more poorly on the Trail Making Test (TMT) and Hopkins Verbal Learning Test-Revised (HVLT-R). In Pre-HD, lower intra-daily variability and higher interdaily stability (more stable, less fragmented rest-activity patterns) were associated with poorer performance on the trail making test Part B, Symbol Digit Modalities Test, Emotion Recognition Task, Rey Complex Figure Test, visual memory task, paced tapping, and HVLT-R total trial. Higher interdaily stability was also linked to poorer HVLT-R performance. Relative amplitude and sleep regularity index were not related to performance. Poorer sleep quality on the Pittsburgh Sleep Quality Index correlated with worse HVLT-R delayed and paced tapping scores. More severe insomnia (higher Insomnia Severity Index scores) correlated with lower Rey Complex Figure Test copy. Conclusions: Our findings emphasize the importance of uninterrupted sleep on cognitive function in Pre-HD and reveal targets for interventions aimed at improving cognitive symptoms. Larger cohorts stratified by proximity to diagnosis are critical to improving our understanding of these relationships across the premanifest period.