Sleep fragmentation despite intact rest-activity patterns in premanifest Huntington's disease: An actigraphy study

Emily S Fitzgerald; Jessica E Manousakis; Yifat Glikmann-Johnston; Meg Rankin; Clare Anderson; Julie C Stout; Melinda L Jackson

doi:10.1016/j.sleep.2024.08.026

Sleep fragmentation despite intact rest-activity patterns in premanifest Huntington's disease: An actigraphy study

Sleep Med. 2024 Aug 31:124:16-29. doi: 10.1016/j.sleep.2024.08.026. Online ahead of print.

Authors

Emily S Fitzgerald¹, Jessica E Manousakis¹, Yifat Glikmann-Johnston¹, Meg Rankin¹, Clare Anderson², Julie C Stout³, Melinda L Jackson¹

Affiliations

¹ School of Psychological Sciences, and Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC, Australia.
² School of Psychological Sciences, and Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC, Australia; Centre for Human Brain Health, School of Psychology, University of Birmingham, Edgbaston, UK.
³ School of Psychological Sciences, and Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC, Australia. Electronic address: julie.stout@monash.edu.

PMID: 39250876
DOI: 10.1016/j.sleep.2024.08.026

Abstract

Objective: Sleep research in Huntington's disease (HD) has primarily focused on manifest HD, with significantly less attention given to premanifest HD (Pre-HD). Therefore, we investigated sleep and rest-activity patterns in people with Pre-HD versus healthy controls (HC).

Methods: We conducted a cross-sectional study including 36 Pre-HD and 48 HC participants. Pre-HD participants were stratified into three groups according to their proximity to estimated diagnosis, using a cytosine-adenine-guanine (CAG) and current age-based predictive model: NEAR (<9 years to diagnosis), MID (9-15 years to diagnosis) and FAR (>15 years to diagnosis). Sleep and rest-activity patterns were assessed using wrist-worn actigraphy, a sleep diary, and sleep questionnaires.

Results: NEAR and MID groups experienced higher fragmentation index than HC and FAR groups. NEAR and MID groups also exhibited greater WASO than the FAR group. NEAR and MID groups showed lower intra-daily variability (IV) than HC and FAR groups, with the NEAR group also being more active in the most active 10 h (M10). Groups did not differ on subjective sleep measures, inter-daily stability (IS), sleep regularity index, relative amplitude, or amount of activity in the least active 5 h (L5). Considering all Pre-HD participants, fewer years to diagnosis, higher CAG-age-product (CAP) scores (a measure of cumulative exposure to the HD-causing gene mutation) and larger CAG repeat lengths correlated with higher WASO, fragmentation index, L5, IS, and lower sleep efficiency and IV. Higher CAP score correlated with higher M10.

Conclusions: Despite intact rest-activity patterns and similar subjective sleep quality to HC, greater sleep fragmentation is a prominent and early feature in Pre-HD. Therefore, reducing sleep fragmentation may be a potential target for sleep intervention in HD. Longitudinal studies using larger samples are needed to assess sleep across the disease spectrum and its impact on clinical outcomes, like cognition.

Keywords: Actigraphy; Dementia; Neurodegenerative disease; Sleep quality.