REM Sleep Behavior Disorder and Biomarkers of Neurodegenerative Disease

Abstract & Commentary

By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports no financial relationships relevant to this field of study.

Synopsis: Biomarkers for Parkinson's disease and related neurodegenerative diseases occur frequently in patients with idiopathic REM sleep behavior disorder. These include impairment of olfactory and color discrimination, and abnormalities in cerebral blood flow.

Source: Vendette M, et al. Brain perfusion and markers of neurodegeneration in rapid eye movement sleep behavior disorder, Movement Disorders 2011 [Epub ahead of print]; doi: 10.1002/mds.23721.

In recent years, there has been a growing recognition that non-motor manifestations of Parkinson's disease (PD) and related disorders develop years — or decades — before the onset of motor symptoms. This "premotor stage" of PD is characterized by symptoms such as constipation, anxiety, hyposmia, impairment of color discrimination, and sleep disorders. A specific parasomnia — rapid eye movement sleep behavior disorder (RBD) — has been closely associated with synucleinopathies such as PD, diffuse Lewy body disease (DLBD), and multiple system atrophy (MSA).

RBD is characterized by loss of muscle atonia during REM sleep, with acting out of the dreams (kicking, punching, shouting, etc.) that can lead to injury to the patient or bed partner. RBD may occur in patients with a known neurodegenerative disorder, but also can occur in the absence of detectable motor or cognitive symptoms ("idiopathic RBD"). With long-term follow-up, however, a large percentage of patients with so-called "idiopathic" RBD go on to develop PD or a related disorder.

In this study, the authors examined cerebral blood flow patterns in idiopathic RBD vs healthy controls, and tested the hypothesis that the specific pattern of abnormal perfusion will correlate with the presence of other established biomarkers for PD (impaired olfactory and color discrimination). The study population consisted of 20 patients with idiopathic RBD (confirmed by polysomnography) and 20 healthy control subjects. Each subject underwent a motor examination, color vision discrimination testing (Farnsworth-Munsell test), olfactory discrimination testing (University of Pennsylvania Smell Identification Test-12 items), and resting-state single-photon emission computerized tomography (SPECT) to evaluate cerebral blood flow. Subjects with parkinsonism on examination, and those with known neurodegenerative disorders, were excluded from participation in the study.

In comparison with healthy controls, subjects with RBD had a pattern of cerebral blood flow similar to that of PD, with decreased perfusion of the frontal cortex and medial parietal areas, and increased perfusion of subcortical regions (including the bilateral pons, putamen, and hippocampus). In RBD, there was also a correlation between: (1) reduced perfusion in frontal and occipital regions with impairment in color discrimination, and (2) reduced perfusion in the bilateral anterior hippocampal gyrus with impairment of olfactory discrimination. The findings confirm the association between RBD, abnormal regional cerebral perfusion, and other biomarkers of PD. In addition, they demonstrate a correlation between individual PD biomarkers and specific patterns of abnormal cerebral perfusion.

Commentary

Given the compelling evidence that PD and related disorders begin many years before the onset of motor symptoms, there has been a heightened interest in the identification of biomarkers for PD. Such biomarkers would allow for future neuroprotective treatments to be administered as early as possible in the disease course, prior to the onset of motor symptoms.

In this study, the authors confirm previous observations that RBD is associated with abnormal patterns of cerebral perfusion and other markers of neurodegenerative disease. They also demonstrate a correlation between specific biomarkers (impaired smell and color discrimination, respectively) and the pattern of cerebral perfusion. Further study, including longitudinal analysis, is warranted to identify which biomarker(s) are of greatest clinical utility in predicting the likelihood and time-course for the future development of a neurodegenerative disorder in patients with "idiopathic" RBD.