Incidence and Progression of Rapid Eye Movement Behavior Disorder in Early Parkinson's Disease

Abstract

BackgroundBackground: Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with neurodegenerative diseases; however, few longitudinal studies assess the individual evolution of RBD and REM sleep without atonia (RWA) in Parkinson's disease (PD). Objectives Objectives: We aimed to evaluate RBD and RWA changes over time as well as potentially influential factors. Methods Methods: RBD and RWA were analyzed using video-supported polysomnography (vPSG) in initially de novo PD patients at baseline and every 2 years for a total of 6 years. The influence of time, age, sex, levodopa equivalent daily dose (LEDD), unified Parkinson's disease rating scale (UPDRS) sum scores, benzodiazepine intake, Mini-Mental State Examination (MMSE) total scores, and dyskinesia on RWA were investigated using mixed-effect models to account for intra-individual correlations. Results Results: After 6 years, vPSG data were available from 98 of the initial 159 de novo PD patients. RBD prevalence increased from 25% at baseline to 52%. Of the 31 PD patients with RBD and valid vPSGs at all time-points, RWA increased from an average of 19% at baseline to 41% at 6-year follow-up modeled to grow by 29.7% every 2 years (P < 0.001). Time was an independent factor (P < 0.001) for RWA increase. Age was an independent factor influencing RWA increase (P = 0.04). Sex, LEDD, UPDRS sum scores, benzodiazepines, MMSE total scores, and dyskinesia did not have any significant influence. Conclusions Conclusions: RBD and RWA increased significantly over time in PD; time and age were independent factors in a prospective cohort. RBD and RWA can be considered PD progression markers.Rapid eye movement (REM) sleep behavior disorder (RBD), a parasomnia characterized by dream-enacting motor behaviors and/or vocalizations, 1,2 is a precursor to neurodegenerative diseases associated with the misprocessing of α-synuclein. 3,4 A recent meta-analysis calculated an annual conversion rate of 6.3% of patients with isolated RBD (iRBD) into any neurodegenerative disease. 5 Data from functional imaging studies 6 highlighted the role of RBD as a premotor manifestation of Parkinson's disease (PD) and as a diagnostic marker for α-synuclein aggregation disorders. A recent study using the REM sleep behavior screening questionnaire tried to identify "probable RBD" and an association was found between motor and cognitive decline in probable RBD patients. 7 In manifest PD, a recent meta-analysis (n = 2462) calculated an overall mean prevalence of RBD of 23.6% in newly diagnosed PD, with a wide range (4.3%-69.4%) most likely because of the lack of polysomnographic validation in all but 1 of the 8 studies. 8 This 1 study comprised the baseline report of our de novo Parkinson (DeNoPa) sleep cohort and identified polysomnographically validated RBD in 25% of newly diagnosed, drug-naïve PD patients. 9 RBD prevalence increased to 43% at 2-year follow-up. 10 In a large cohort of PD patients at various

Dysautonomia and REM sleep behavior disorder contributions to progression of Parkinson’s disease phenotypes

“…There is high correlation of PSG-proven RBD with the RBD questionnaire results, although with variability 30 – 33 . Since PSG is often performed only once, the RBD questionnaire may be more sensitive to detect RBD, particularly for question 6, which assesses REM sleep behaviors, though is less specific 34 , 35 . Most studies have defined these subjects with subjective dream-enactment behavior without PSG confirmation of REM atonia as having probable RBD (pRBD), and we will use the term pRBD to be consistent with the literature.…”

White matter microstructure in Parkinson’s disease with and without elevated REM sleep muscle tone

“…Studies that have estimated the prevalence of RBD and/or RSWA in PD have shown that a large proportion of people with Parkinson's disease, including those with more advanced disease, do not have RBD or RSWA. [1][2][3][4][5][6][7][8] Accordingly, we speculate that the majority of individuals in our PD-RSWA group will not develop RSWA or RBD, but motor and cognitive impairment will continue to progress along with decreasing FA. This hypothesis implies that the alterations in corticofugal and corticocortical white matter FA observed in this study impact motor and cognitive function, but not the REM sleep atonia circuitry.…”

“…In people with Parkinson's disease, muscle activity during REM sleep is often abnormally elevated (termed REM sleep without atonia, RSWA) and when observed in conjunction with dream enactment (complex movements or vocalizations) reflects the co-expression of REM Sleep Behavior Disorder (RBD). [1][2][3][4][5][6][7][8] Isolated RBD is recognized as a prodromal stage of overt synucleinopathy with approximately 75% of individuals eventually phenoconverting to Parkinson's disease, dementia with Lewy Bodies, or multiple system atrophy within 12 years. 9 While isolated RBD is estimated to be present in about 1% of the population, 10 approximately 30-50% of individuals with Parkinson's disease meet clinical criteria for diagnosis of RBD based on polysomnography-derived evidence of RSWA and dream enactment behavior.…”

Longitudinal Studies of Sleep Disturbances in Parkinson’s Disease

“…These earlier studies in PD which have not studied RBD with the vPSG have since been superseded by studies utilizing vPSG at multiple time points and have conclusively demonstrated that RBD, which is characterized by REM sleep without atonia (RSWA), is a persistent and progressive feature in RBD. Using vPSG, the DeNoPa study group showed that the RBD prevalence had increased from 25% at baseline to 43% at 2-year follow-up [ 30 ••] and to 52% at 6-year follow-up [ 28 ]. RSWA was independently associated with disease duration and age but not other disease-related factors, suggesting that RSWA could be a progression marker.…”

“…The authors have also introduced the concept of REM behavioral events (RBE), where REM-associated minor motor behaviors and/or vocalizations were seen but the RSWA were below cut-off values. In their series, 31 subjects identified to have RBE at baseline developed full-blown RBD within 6 years [ 28 ]: 38% of RBE positive PD subjects converted to RBD, and 18% of PD subjects with normal REM sleep at baseline converted to RBD over 2 years [ 30 ••]. The prevalence of RBE had also increased over time from 50% at baseline to 63% 2 years later [ 30 ••].…”