Paralysis is not always a bad thing—during sleep, it is essential to prevent us from acting out our dreams, for example, by physically tackling the “bear” we’re fighting off. But that paralysis is lost in a condition called rapid eye movement (REM) sleep behavior disorder, or RBD. “People will be moving while dreaming—punching or kicking,” said Bradley Boeve of the Mayo Clinic in Rochester, Minnesota. Studies have suggested RBD precedes α-synucleinopathies, and in the July 28 Neurology online, Boeve and colleagues report that RBD can appear up to half a century before dementia. If and when scientists develop therapies to stave off neurodegeneration, advance warning signs such as RBD could help doctors provide treatment as early as possible. A person’s paralysis lost in early years could then translate to paradise regained if doctors can recognize the signs and prevent dementia in later life.

Neurologists often hear, anecdotally, that someone with PD or related neurodegeneration has acted out dreams for years or longer. “We were struck by the lengthy nature of the sleep disorder prior to the development of a neurodegenerative disorder,” Boeve said. The condition affects both men and women, but is more common in men. In fact, wives of patients sometimes report that they first discovered RBD symptoms during their honeymoon. Studies and surveys indicate a wide range of RBD frequencies in the general population, Boeve said, ranging from less than 1 percent to as many as 9 percent of people. Some studies may come up with a lowball number, he noted, because wives are wary to admit the problem for fear their husbands will be prosecuted for battery. Neurologists may sometimes miss the connection, since patients with parkinsonism do not always think to bring up sleep disturbances during an exam.

Boeve and colleagues designed a retrospective study to confirm links between anecdotal reports of long-term RBD and α-synucleinopathies. First author Daniel Claassen, now at the University of Virginia in Charlottesville, searched five years’ worth of Mayo Clinic records for people who had either PD, DLB, multiple system atrophy, or mild cognitive impairment, plus clinically confirmed RBD. Of those 550 people, 27 had RBD stretching back 15 years or more prior to their neurodegeneration diagnosis.

The study extends the time frame between RBD onset and the appearance of neurodegenerative symptoms. “Some of these folks even had the sleep disorder for close to 50 years,” Boeve said. According to the clinical records, the median time between onset of RBD and onset of further degeneration was 25 years, with a range of 15-50 years. RBD started any time between age 21 and age 60, with a median age of onset of 49. The results fit well with a 2009 prospective study, which found that approximately half of people with RBD would develop PD or LBD within 12 years (Postuma et al., 2009).

Boeve suggests there is a slow, creeping process of pathology that hits the brainstem, where important REM sleep circuits are located, before it progresses to the midbrain and cortex, causing waking symptoms. “The pathogenic process may span most of the lifetime,” the authors write.

The data do not necessarily mean that everyone with RBD will develop a neurodegenerative disease, Boeve said, although the risk appears to be high. Risk data are sparse, but Boeve estimated that more than half of people with RBD are at risk for dementia. He and his coauthors also noted the possibility that all RBD patients would develop further illness if they lived long enough.

If this hypothesis is correct, it has important clinical implications, wrote Arvid Rongve, of Haugesund Hospital in Norway, in an e-mail to ARF. The work could mean there is a huge window of time in which to intervene and, hopefully, prevent or delay the cognitive decline associated with α-synucleinopathies. Rongve has collaborated with Boeve on other research.—Amber Dance.

Reference:
Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010 Jul 28. Abstract

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References

Paper Citations

  1. . Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009 Apr 14;72(15):1296-300. PubMed.
  2. . REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010 Aug 10;75(6):494-9. PubMed.

Further Reading

Papers

  1. . Frequency and case identification of dementia with Lewy bodies using the revised consensus criteria. Dement Geriatr Cogn Disord. 2008;26(5):445-52. PubMed.
  2. . Caregiver reports of sleep problems in non-Hispanic white, Hispanic, and African American patients with Alzheimer dementia. J Clin Sleep Med. 2010 Jun 15;6(3):281-9. PubMed.
  3. . Frequency and correlates of caregiver-reported sleep disturbances in a sample of persons with early dementia. J Am Geriatr Soc. 2010 Mar;58(3):480-6. PubMed.
  4. . Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996 Feb;46(2):388-93. PubMed.
  5. . Core and suggestive symptoms of dementia with lewy bodies cluster in persons with mild dementia. Dement Geriatr Cogn Disord. 2010;29(4):317-24. PubMed.
  6. . REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010 Aug 10;75(6):494-9. PubMed.
  7. . Expression of inducible nitric oxide synthase (iNOS) and period 1 (PER1) clock gene products in different sleep stages of patients with cognitive impairment. J Clin Neurosci. 2010 Sep;17(9):1140-3. PubMed.
  8. . Temporal course of depressive symptoms during the development of Alzheimer disease. Neurology. 2010 Jul 6;75(1):21-6. PubMed.

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Primary Papers

  1. . REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010 Aug 10;75(6):494-9. PubMed.