Lack of good sleep is a major problem in Huntington's disease (HD). Further, the degree of sleep disturbance correlates with levels of fatigue, depression, cognitive impairment, harmful metabolic or energy factors, and degree of damage seen on brain scans. Bad sleep is bad news. But the good news, at least in HD-mouse models, is that rigidly scheduled "environmental entrainment" can improve several of these factors. To put this in perspective: the level of benefit is far greater than that reported for any supplement or drug tested in mice.

And best news? HD individuals can do this too, and if the experts are correct we'll not only feel and think better, we may slow progression of the disease.

Sleep deprivation in healthy people causes profound effects on health and quality of life. It impairs memory, interferes with learning (for which there is a lack of awareness), reduces physical (motor) and mental reaction times, reduces motivation, increases depression, increases irritability, changes levels of stress hormones (like cortisol) and causes harmful metabolic abnormalities similar to those observed in HD [Foster RG 2005].

Sleep studies in HD individuals All in HD families are well aware of what scientists have described: sleep is very disordered in HD individuals. and as consequence also affects live-in care partners [Hurelbrink CB 2005]. Similar to other neurodegenerative diseases [Chokroverty S 1996], HD-related sleep complaints are many and can include:

  • difficulty falling asleep
  • frequent awakenings
  • poor quality sleep
  • longer hours in bed
  • day-time fatigue
  • poor concentration
  • depression
  • muscle aches

Studies in HD individuals show that the magnitude of sleep disturbance correlates with depression, loss of cognitive or thinking ability, and degree of damage seen on brain scans [Aziz NA 2010]. Further studies in HD individuals show an abnormal blood level pattern for melatonin [Aziz NA 2009], a hormone important to circadian rhythm (sleep-awake) cycles, and abnormal levels of genes known to regulate sleep patterns and metabolism.

Studies in mouse and rat models: HD-mouse models have quite similar sleep disturbances. Dr. Jenny Morton, a scientist at the forefront in the study of sleep disturbance in HD has described 2 major pathways -- including a harmful one related to metabolic energy -- of altered biology related to sleep disturbance in R6/2 HD mice [Maywood ES 2010]. Similar changes have been reported in other HD models [Oakeshott S 2011]. Further, sleep deprivation in the healthy rat causes metabolic changes that lead to muscle atrophy similar to that seen in HD [Dattilo M 2012].

In the next pivotal step, Dr. Morton showed that cognition and apathy related symptoms of HD mice improve with "environmental entrainment" or regularly scheduled light/dark cycles and specific feeding times [Maywood ES 2010]. Further, molecular markers and genes associated with circadian rhythm and metabolic markers normalized.

What about people? If it is possible to treat the sleep problem in HD in mice and improve symptoms, might treating the sleep disorder in people reduce severity of symptoms and perhaps even slow progression of disease? Though this is yet to be proved, it's certainly worth the try. What is the best sleep prescription? Following Dr. Morton's entrainment paradigm for mice, it means changing our bad habits. How important might this be? The benefit seen in improving sleep patterns is far greater than that for any supplement tested in mice.

  • Light/dark cycling or same time to bed (in darkened room) and same time of awakening each AM
  • Bright light therapy most useful during the dark season(see Mayo Clinic light box recommendations)
  • Same time every day for meals. No all day snacking
  • Last full meal several hours before bedtime. Small bedtime snack at most
  • Regular exercise at the same time of day (but not within 2 hours of bedtime)
  • Daytime social and environmental stimulation

Other general factors:

  • No caffeine after mid day meal
  • Either no alcohol or 1 drink, but none within 2 hours of bedtime
  • Quiet bedroom with no TV or phone

Sleep medications to consider:

  • Low dose melatonin (Experts favor low dose O.5 to 1 mg) taken 2 hours before bedtime appears to have benefit when combined with light therapy.
  • Trazodone, a prescription sleep aid commonly used by HD experts appears to have positive effect and low side effects in studies of neruodegenerative disease [Zhou QP 2012].
  • Though alprazolam (Xanax®) reversed melatonin abnormalities in the mouse [Pallier PN 2007], this same effect does not occur in people. Also, this type of drug will result in decreased alertness on awakening.
  • Though SSRI antidepressant medication can improve sleep in depression and anxiety, it can also decrease REM sleep time in others.

Author's comments: There is no easy fix or magic pill for sleep problems in HD. It will take hard work from HD individuals and families, but will improve the quality of life for all in HD families. You will need an alarm, light box or other system that wakes you up at the same time, and you will need to get out of bed even though you are still tired. You must go to bed at the same time even if it takes more time to get to sleep, and don't add "make up" time spent falling asleep with extra sleep time in the morning. Stick to this pattern every day. Don't expect it to work overnight: In mice it takes several days to change the pattern -- in people it will take longer.


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