54 Sleep and Circadian Rhythms in Premanifest Huntington’s disease: Relationship with Cognition
Authors: Fitzgerald Emily S 
Published: December 2023

Objective:Huntington’s disease (HD) is a neurodegenerative disease characterised by motor, psychiatric and cognitive decline. Currently, no treatments have been identified in HD for slowing down cognitive decline or improving cognitive function. We are interested in identifying potentially modifiable factors in HD that can be targeted to improve or maintain cognitive function. Sleep and circadian disruption stand out as possible modifiable targets because sleep and circadian symptoms are common in HD, and such disruptions are known to impact cognition in the general population. Despite some emerging evidence that sleep quality correlates with cognition in manifest HD, whether these same relationships exist in the premanifest period is unknown. Further, whether circadian rhythms relate to cognition in premanifest HD remains open. Therefore, we aimed to determine whether sleep and circadian parameters relate to cognitive performance in premanifest HD.Participants and Methods:To date, we have recruited 27 premanifest HD participants to a two-week remote sleep study. During the study, participants wore an Actiwatch-2 and completed a sleep diary for 14 consecutive days to assess their sleep and rest-activity patterns. Participants also completed online sleep and mood questionnaires and a cognitive assessment using videoconference. We calculated Pearson correlations to examine whether cognitive performance relates to subjective sleep quality, objective sleep parameters and circadian rest-activity rhythms. Thus far, we have analysed data from 15 female participants with premanifest HD (Mage = 43.20, SD = 11.58).Results:Preliminary results indicate that measures of subjective sleep quality, insomnia severity, daytime sleepiness, and fatigue severity in premanifest HD do not correlate with cognitive performance. Increases in objectively measured sleep efficiency, however, strongly correlated with better performance on the Hopkins-Verbal Learning Test-Revised (HVLT-R) immediate (r = 0.562, p < 0.05) and delayed recall trials (r = 0.597, p < 0.05) and the Trail Making Test Part B (TMT-B; r = 0.550, p < 0.05). More time spent awake (i.e., wake after sleep onset) was strongly linked to reduced performance on the TMT-B (r = -0.542, p < 0.05) and Symbol Digit Modalities Test (r = -0.556, p < 0.05). Further, increases in total sleep time were associated with better performance on the HVLT-R immediate (r = 0.682, p < 0.05) and delayed recall trial (r = 0.616, p < 0.05). For our circadian parameters, less fragmented day-today rest-activity rhythms (i.e., higher intra-daily variability) strongly correlated with higher scores on the HVLT-R immediate (r = 0.768, p < 0.001) delayed recall trials (r = 0.7276, p < 0.05) and TMT-B (r = 0.516, p < 0.05), whereas consistent and stable day-to-day rest-activity rhythms (i.e., higher inter-daily stability) was associated with poorer performance on ERT (r = -0.587, p < 0.05).Conclusions:Preliminary results suggest that fragmented sleep, sleep inefficiency, reduced total sleep time, rest-activity rhythm stability and fragmentation relate to poorer cognitive performance in people with premanifest HD. Should analysis of our whole sample confirm these preliminary findings, targeting sleep in HD (e.g., through sleep hygiene and/or psychoeducation) may be a useful strategy to improve or maintain cognition.