The Healing Power of Sleep | Print |  Email

Posted March 12, 2012 by LaVonne Goodman M.D.

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 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 2005]. Similar to other neurodegenerative diseases [Chokroverty 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 2010]. Further studies in HD individuals show an abnormal blood level pattern for melatonin [Aziz 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 2010].  Similar changes have been reported in other HD models [Oakeshott 2011].  Further, sleep deprivation in the healthy rat causes metabolic changes that lead to muscle atrophy similar to that seen in HD [Dattilo 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 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 2012].
  • Though alprazolam (Xanax) reversed melatonin abnormalities in the mouse [Pallier 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.

References

Foster RG, Wulff K. The rhythm of rest and excess. Nat Rev Neurosci 2005 May;6(5):407-14. PubMed abstract

Hurelbrink CB, Lewis SJ, Barker RA. The use of the Actiwatch-Neurologica system to objectively assess the involuntary movements and sleep-wake activity in patients with mild-moderate Huntington's disease. J Neurol 2005 Jun;252(6):642-7. PubMed abstract

Chokroverty S. Sleep and degenerative neurologic disorders. Neurol Clin 1996 Nov;14(4):807-26. PubMed abstract

Aziz NA, Anguelova GV, Marinus J, Lammers GJ, Roos RA. Sleep and circadian rhythm alterations correlate with depression and cognitive impairment in Huntington's disease. Parkinsonism Relat Disord 2010 Jun;16(5):345-50. PubMed abstract

Aziz NA, Pijl H, Fr÷lich M, Schr÷der-van der Elst JP, van der Bent C, Roelfsema F, Roos RA. Delayed onset of the diurnal melatonin rise in patients with Huntington's disease. J Neurol 2009 Dec;256(12):1961-5. PubMed abstract

Maywood ES, Fraenkel E, McAllister CJ, Wood N, Reddy AB, Hastings MH, Morton AJ. Disruption of peripheral circadian timekeeping in a mouse model of Huntington's disease and its restoration by temporally scheduled feeding. J Neurosci 2010 Jul 28;30(30):10199-204. PubMed abstract

Oakeshott S, Balci F, Filippov I, Murphy C, Port R, Connor D, Paintdakhi A, Lesauter J, Menalled L, Ramboz S, Kwak S, Howland D, Silver R, Brunner D. Circadian Abnormalities in Motor Activity in a BAC Transgenic Mouse Model of Huntington's Disease. PLoS Curr 2011;3():RRN1225. PubMed abstract

Dattilo M, Antunes HK, Medeiros A, M˘nico-Neto M, Souza Hde S, Lee KS, Tufik S, de Mello MT. Paradoxical sleep deprivation induces muscle atrophy. Muscle Nerve 2012 Mar;45(3):431-3. PubMed abstract

Zhou QP, Jung L, Richards KC. The Management of Sleep and Circadian Disturbance in Patients with Dementia. Curr Neurol Neurosci Rep 2012 Feb 8;():. PubMed abstract

Pallier PN, Maywood ES, Zheng Z, Chesham JE, Inyushkin AN, Dyball R, Hastings MH, Morton AJ. Pharmacological imposition of sleep slows cognitive decline and reverses dysregulation of circadian gene expression in a transgenic mouse model of Huntington's disease. J Neurosci 2007 Jul 18;27(29):7869-78. PubMed abstract

 
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