Severity of REM atonia loss in idiopathic REM sleep behavior disorder predicts Parkinson disease

Background: Over 50% of persons with idiopathic REM sleep behavior disorder (RBD) will develop Parkinson disease (PD) or dementia. At present, there is no way to predict who will develop disease. Since polysomnography is performed in all patients with idiopathic RBD at diagnosis, there is an opportunity to analyze if baseline sleep variables predict eventual neurodegenerative disease. Methods: In a longitudinally studied cohort of patients with idiopathic RBD, we identified those who had developed neurodegenerative disease. These patients were matched by age, sex, and follow-up duration to patients with RBD who remained disease-free and to controls. Polysomnographic variables at baseline (i.e., before development of neurodegenerative disease) were compared between groups. Results: Twenty-six patients who developed neurodegenerative disease were included (PD 12, multiple system atrophy 1, dementia 13). The interval between polysomnogram and disease onset was 6.7 years, mean age was 69.5, and 81% were male. There were no differences between groups in sleep latency, sleep time, % stages 2–4, % REM sleep, or sleep efficiency. However, patients with idiopathic RBD who developed neurodegenerative disease had increased tonic chin EMG activity during REM sleep at baseline compared to those who remained disease-free (62.7 ± 6.0% vs 41.0 ± 6.0%, p = 0.020). This effect was seen only in patients who developed PD (72.9 ± 6.0% vs 41.0 ± 6.0%, p = 0.002), and not in those who developed dementia (54.3 ± 10.3, p = 0.28). There was no difference in phasic submental REM EMG activity between groups. Conclusions: In patients with REM sleep behavior disorder initially free of neurodegenerative disease, the severity of REM atonia loss on baseline polysomnogram predicts the development of Parkinson disease.

[1]  S Minoshima,et al.  Diagnosis and management of dementia with Lewy bodies , 2005, Neurology.

[2]  R. Postuma,et al.  Idiopathic REM sleep behavior disorder in the transition to degenerative disease , 2009, Movement disorders : official journal of the Movement Disorder Society.

[3]  H. Stähelin,et al.  Seventy-two hour polygraphic and behavioral recordings of wakefulness and sleep in a hospital geriatric unit: comparison between demented and nondemented patients. , 1987, Sleep.

[4]  Jacques Montplaisir,et al.  Polysomnographic features of REM sleep behavior disorder , 1992, Neurology.

[5]  R. Spiegel,et al.  Polygraphic sleep criteria as predictors of successful aging: an exploratory longitudinal study , 1999, Biological Psychiatry.

[6]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[7]  M. Mahowald,et al.  REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. , 2002, Sleep.

[8]  H. Weingartner,et al.  Disturbances of sleep and cognitive functioning in patients with dementia , 1982, Neurobiology of Aging.

[9]  S. Lange,et al.  Adjusting for multiple testing--when and how? , 2001, Journal of clinical epidemiology.

[10]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[11]  J. Yesavage,et al.  REM latency in Alzheimer's disease , 1989, Biological Psychiatry.

[12]  J. Montplaisir,et al.  Neurobiology of sleep disturbances in neurodegenerative disorders. , 2008, Current pharmaceutical design.

[13]  M. Vitiello,et al.  Factors associated with concordance and variability of sleep quality in persons with Alzheimer's disease and their caregivers. , 2008, Sleep.

[14]  José Luis Molinuevo,et al.  Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study , 2006, The Lancet Neurology.

[15]  M W Mahowald,et al.  Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. , 2007, Brain : a journal of neurology.

[16]  E. Wolpert A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. , 1969 .

[17]  A. Lang,et al.  Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder , 2006, Neurology.

[18]  E. Tolosa,et al.  Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD , 2005, Neurology.

[19]  G. Halliday,et al.  The progression of pathology in longitudinally followed patients with Parkinson’s disease , 2008, Acta Neuropathologica.

[20]  Julien Doyon,et al.  Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases , 2006, The Lancet Neurology.

[21]  B. Boeve,et al.  Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson’s disease over time , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[22]  Mark W. Mahowald,et al.  Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder , 1996, Neurology.

[23]  Joan Santamaria,et al.  Excessive muscle activity increases over time in idiopathic REM sleep behavior disorder. , 2009, Sleep.

[24]  E. Tolosa,et al.  Diagnostic procedures for Parkinson's disease dementia: Recommendations from the movement disorder society task force , 2007, Movement disorders : official journal of the Movement Disorder Society.

[25]  S. Redline,et al.  The effects of age, sex, ethnicity, and sleep-disordered breathing on sleep architecture. , 2004, Archives of internal medicine.

[26]  R. Hu Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , 2003 .

[27]  M. Vendette,et al.  Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder , 2009, Neurology.