Prodromal Parkinson's disease--using REM sleep behavior disorder as a window.

REM sleep behavior disorder (RBD) is characterized by loss of REM atonia of sleep, such that patients act out the contents of their dreams. Perhaps the most important facet of idiopathic RBD is that it is a powerful prodromal marker of Parkinson's disease (PD) and other synucleinopathies. Several prospective studies have now established that patients with idiopathic RBD have up to an 80% risk of developing a defined neurodegenerative synucleinopathy. This has profound implications for understanding and treating early disease. First, the extremely high risk and long latency/time to intervene make RBD patients the ideal candidates for neuroprotective therapy against synucleinopathy. Second, RBD patients can be used as a 'test lab' to assess other potential prodromal predictors of PD, which could be applied to the general population in future large-scale screening programs. Third, assessing epidemiology of RBD allows us to study the epidemiology of PD and dementia with Lewy bodies 10-15 years earlier, reducing bias and opening new hypotheses as to the mechanism of action of selected risk factors. Finally, by prospectively observing RBD patients as they transition to full neurodegenerative synucleinopathy, one has an unprecedented window in which to directly observe evolution of PD from its prodromal stages. The evidence for RBD as a marker of prodromal PD and all these implications will be discussed.

[1]  C. Adler,et al.  Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. , 2013, Sleep medicine.

[2]  R. Postuma,et al.  Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder , 2011, Movement disorders : official journal of the Movement Disorder Society.

[3]  Véronique Latreille,et al.  Rapid eye movement sleep behavior disorder and subtypes of Parkinson's disease , 2012, Movement disorders : official journal of the Movement Disorder Society.

[4]  J. Molinuevo,et al.  Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study , 2013, The Lancet Neurology.

[5]  V. Mok,et al.  Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK). , 2010, Sleep medicine.

[6]  J. Molinuevo,et al.  Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study , 2010, The Lancet Neurology.

[7]  W. Oertel,et al.  Identifying prodromal Parkinson's disease: Pre‐Motor disorders in Parkinson's disease , 2012, Movement disorders : official journal of the Movement Disorder Society.

[8]  A. Desautels,et al.  Family history of idiopathic REM behavior disorder , 2013, Neurology.

[9]  Joan Santamaria,et al.  The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases. , 2009, Sleep medicine reviews.

[10]  R. Postuma,et al.  Severity of REM atonia loss in idiopathic REM sleep behavior disorder predicts Parkinson disease , 2010, Neurology.

[11]  V. Pankratz,et al.  Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies , 2011, Neurology.

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

[13]  V. Pankratz,et al.  Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: A population‐based study , 2012, Annals of neurology.

[14]  J. Molinuevo,et al.  Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study , 2011, The Lancet Neurology.

[15]  W. Oertel,et al.  Environmental risk factors for REM sleep behavior disorder , 2012, Neurology.

[16]  R. Postuma,et al.  Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson's disease. , 2009, Brain : a journal of neurology.

[17]  Kevin F. Bieniek,et al.  Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. , 2013, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[18]  R. Postuma,et al.  Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder , 2011, Annals of neurology.

[19]  K. Hirata,et al.  Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder , 2006, Neurology.

[20]  A. Lang,et al.  How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. , 2012, Brain : a journal of neurology.

[21]  D. Navajas,et al.  Electroencephalographic slowing heralds mild cognitive impairment in idiopathic REM sleep behavior disorder. , 2010, Sleep medicine.

[22]  Carlos H Schenck,et al.  Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. , 2013, Sleep medicine.

[23]  H. Braak,et al.  Invited Article: Nervous system pathology in sporadic Parkinson disease , 2008, Neurology.

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

[25]  Poul Jennum,et al.  A single‐question screen for rapid eye movement sleep behavior disorder: A multicenter validation study , 2012, Movement disorders : official journal of the Movement Disorder Society.

[26]  M. Mahowald,et al.  Delayed emergence of a parkinsonian disorder or dementia in 81% of older males initially diagnosed with idiopathic REM sleep behavior disorder (RBD): 16 year update on a previously reported series , 2013 .

[27]  R. Postuma,et al.  Prodromal autonomic symptoms and signs in Parkinson's disease and dementia with Lewy bodies , 2013, Movement disorders : official journal of the Movement Disorder Society.

[28]  T. Dang-Vu,et al.  Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder , 2012, Neurology.

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

[30]  V. Mok,et al.  Prospective outcome of rapid eye movement sleep behaviour disorder: psychiatric disorders as a potential early marker of Parkinson's disease , 2012, Journal of Neurology, Neurosurgery & Psychiatry.