REM Sleep Behavior Disorder Predicts Rapid Motor and Cognitive Decline in Parkinson’s Disease

Among people with Parkinson’s disease, REM sleep behavior disorder (RBD) is associated with more rapid motor progression in patients with high levels of synuclein and dopaminergic pathology, according to research published online ahead of print August 8 in Neurology. RBD also indicates an increased risk of cognitive decline in patients with high degrees of synuclein and amyloid pathology.

“Our study is the first to link the predictive value of RBD symptoms to the presence of amyloid and synuclein pathology,” said Marios Politis, MD, PhD, Lily Safra Professor of Neurology and Neuroimaging, Consultant Neurologist, and the Director of the Neurodegeneration Imaging Group at King’s College London, and colleagues. “Measuring dopaminergic dysfunction and amyloid and synuclein burden in the screening of patients with RBD at an early stage of Parkinson’s disease, possibly even at the premotor phase of disease, could potentially identify the ones more likely to progress and develop dementia.”

Marios Politis, MD, PhD

The prevalence of RBD in patients with Parkinson’s disease ranges between 35% and 60%. Longitudinal data indicate that RBD is associated with faster development of cognitive decline and a greater risk of mild cognitive impairment and dementia in patients with Parkinson’s disease. Dr. Politis and colleagues examined the risk of motor progression and cognitive decline in patients with Parkinson’s disease and RBD who are untreated and at an early stage after disease onset.

The investigators selected 421 untreated patients with Parkinson’s disease and 196 healthy controls from the Parkinson’s Progression Markers Initiative database for their analysis. Eligible participants presented for screening at less than two years after diagnosis. Patients underwent a [123I]FP-CIT SPECT scan, CSF assessment, 3-T MRI, and thorough clinical assessments.

Among participants with Parkinson’s disease, average age was about 61 at baseline. Approximately 66% of these participants were male, and their mean disease duration was about 6.6 years. Patients with RBD had poorer olfaction, a higher burden of nonmotor symptoms, and worse scores on neuropsychologic tests. Furthermore, patients with RBD had lower CSF amyloid β42 levels and higher ratios of total tau to amyloid β42, compared with patients without RBD.

During 60 months of follow-up, RBD was associated with faster motor progression (hazard ratio [HR], 1.368) and cognitive decline (HR, 1.794). RBD predicted motor progression only in patients with Parkinson’s disease who had low α-synuclein levels and low [123I]FP-CIT uptake in the striatum (HR, 2.091). RBD predicted cognitive decline only in patients with Parkinson’s disease who had low amyloid β42 and low α-synuclein levels (HR, 2.810). RBD was not associated with cognitive decline or pathologic changes among healthy controls.

Parkinson’s disease with RBD “was previously suggested as a specific Parkinson’s disease phenotype associated with faster motor progression and characterized by reduced tremor, high frequency of falls, and a lower amplitude of response to medication dose,” said Dr. Politis and coauthors. “Our findings extend these observations and indicate that the Parkinson’s disease-RBD phenotype may vary in terms of progression of motor or cognitive symptoms, depending on underlying α-synuclein, amyloid β, and dopaminergic pathology."

—Erik Greb

Suggested Reading

Pagano G, De Micco R, Yousaf T, et al. REM behavior disorder predicts motor progression and cognitive decline in Parkinson disease. Neurology. 2018 Aug 8 [Epub ahead of print].