In Huntington’s Disease, How Sleep and Circadian Patterns Affect Cognition
—In patients with Huntington’s disease, poorer sleep is associated with poorer cognitive function. But would these patients benefit from targeted sleep and circadian rhythm modification to improve cognitive function?
Poor sleep is associated with worse cognitive outcomes in patients with Huntington’s disease (HD), according to a newly published review.1 Emily Fitzgerald, PhD Candidate, with Monash University, in Victoria, Australia, and colleagues, reported their findings August 14, 2023, in Journal of Huntington’s Disease.
HD is a progressive and fatal neurodegenerative disorder with autosomal dominant inheritance. The disease is caused by a CAG repeat expansion in the huntingtin gene, with approximately 40 repeats being necessary for clinical disease. Typical onset is during the third to fifth decades of life. An increasing number of CAG repeats is associated with earlier age of onset.2
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Persons with HD experience a wide range of motor, psychiatric, and cognitive symptoms. Motor defects include chorea, loss of coordination, and speech and swallowing difficulties. Psychiatric symptoms related to depression, psychosis, and anxiety are both common and very distressing for persons with HD.2
Cognitive impairment emerges with disease progression, but some patients have evidence of cognitive impairment up to a decade prior to diagnosis.2 These cognitive impairments may manifest as changes in psychomotor speed, information processing speed, emotional recognition, social cognition, visuospatial processing, visuomotor integration, executive function, attention, and memory.1
Sleep disturbances are also common among persons with HD,3 and these sleep disturbances negatively impact cognitive function and level of independence.4
The authors of this review wanted to determine whether interventions designed to improve sleep or circadian rhythms could positively impact cognitive function in persons with HD. To address this question, the researchers performed a comprehensive review and evidence synthesis of the published literature.
Sleep and circadian rhythm disturbances in HD
During the premanifest period of HD, there is objective evidence of decreased sleep efficiency, with fragmentation, increased wakefulness, and intermittent nocturnal arousals. In manifest HD, there is impaired sleep quality, more time in bed, sleep fragmentation, reduced sleep efficiency, longer latency to rapid eye movement sleep, and changes to sleep microarchitecture and microarchitecture.
Circadian rhythm abnormalities in HD include abnormal blood pressure patterns during sleep, differences in diurnal cortisol patterns, and disruptions to typical melatonin concentrations and onset of evening melatonin.
Sleep and cognitive function
Among patients with HD, polysomnography has been used to show that longer sleep onset latency is associated with poorer performance on the Luria sequential motor task and that less stage 3 sleep and more stage 1 sleep are associated with poorer performance on the Wechsler Adult Intelligence Scale.
Actigraphy has shown that those with HD who spend more time in bed are less accurate and slower in tests of visual memory as well.
Results have been more mixed in studies employing self-reported sleep disturbance and objective measures of cognitive performance. However, self-reported poor sleep quality has been associated with depression among those with HD.
Circadian markers and cognitive function
Self-reported bed and wake times have been used as a proxy for circadian timing by those studying cognitive function in HD. These investigations have revealed that later morning wake times correlate with poorer cognitive scores. However, later wake times are also associated with higher anxiety and depression scores. Overall, there has been little investigation into possible relationships between circadian rhythms and cognitive function in HD.
Next steps
“To advance knowledge in sleep, circadian rhythms, and cognitive function in HD, we must establish causal links, assess sleep and circadian rhythms across the disease spectrum, and consider additional methodological factors such as the cognitive assessment, sleep and circadian measurement methods, and adjusting for key covariates,” write the researchers.
According to the research team, randomized controlled trials are needed to manipulate sleep and circadian patterns to determine whether interventions may improve cognitive function among those with HD. Furthermore, little study has been undertaken to examine impacts of sleep and circadian patterns in premanifest and advanced stages of HD.
With respect to measurement, the researchers emphasize that cognitive assessments should include decision making, behavioral inhibition, learning, memory, and sustained attention. Circadian measurement studies would benefit from the minimization of external confounders such as sleep, lighting, stress, exercise, posture, diet, and social factors. Additionally, melatonin should be further investigated as a circadian marker in HD.
Though sleep measurement is typically performed using polysomnography, the researchers advocate for the incorporation of ambulatory sleep measures in more natural home settings to help evaluate sleep disturbance and impaired cognitive function.
Lastly, because of the potential impacts of mood disorders and medications on sleep, circadian rhythms, and cognitive function, future studies should adjust for these covariates when investigating relationships in patients with HD.
“Current research is severely limited and lacks essential evidence to progress the field,” write the researchers. Because “Sleep and circadian rhythms may serve as modifiable targets to improve cognitive function in HD.”
“Controlled studies across the disease spectrum, utilizing accurate sleep and circadian measurements, targeted cognitive batteries, and adjusting for essential covariates, are critical to clearly delineate links between cognitive dysfunction and sleep or circadian disruption in HD.”
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