Circadian rhythm and autonomic dysfunction in presymptomatic and early Huntington's disease

Abstract

Introduction: Sleep and circadian rhythm disturbances are common in patients with neurodegenerative diseases such as Huntington's disease (HD). The aim of this study was to evaluate variability in circadian blood pressure (BP) to determine the association between abnormal circadian BP and sleep quality in patients with HD.

Methods: Cross-sectional, multicenter study of 38 HD mutation carriers (23 premanifest and 15 early stage patients) who were compared to 38 age- and sex-matched controls. BP was evaluated by ambulatory blood pressure monitoring (ABPM). Based on the percentage decrease in nocturnal BP, subjects were classified as either dippers (≥10%) or non-dippers (<10%). Sleep quality and daytime sleepiness were measured, respectively, using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Daytime Sleepiness Scale (ESS) and the scores on these indices were correlated with the ABPM findings.

Results: Sixty-three percent HD mutation carriers were non-dippers (86.7% of the symptomatic and 47.8% of the premanifest patients) versus 23.7% of controls (p = 0.001). In the HD group, sleep quality was significantly more impaired (PSQI>5) (p = 0.016) with more excessive daytime sleepiness (ESS>9) (p = 0.001) than in the control group. Nocturnal non-dipping was associated with worse sleep quality in patients (p = 0.011) but not in controls.

Conclusion: These results show that patients with HD present early disturbances in the circadian rhythm of BP and that this altered nocturnal BP is associated with poor sleep quality. These findings suggest the potential role of subtle hypothalamic dysfunction in this population.

Keywords: Circadian rhythm; Huntington's disease; Hypothalamus; Sleep; Suprachiasmatic nucleus.