Association Between REM Sleep Behavior Disorder and Cognitive Dysfunctions in Parkinson's Disease: A Systematic Review and Meta-Analysis of Observational Studies

Abstract

Background: Rapid eye movement sleep behavior disorder (RBD) is thought to be a prodromal symptom of Parkinson's disease (PD). RBD is also thought to be involved in cognitive decline and dementia in PD. In PD, although the relationship between RBD and cognitive dysfunctions was confirmed by considerable studies, whether RBD was associated with distinct types of cognitive defects is worth of study. Objectives: This systematic review summarizes the evidence relating to cognitive dysfunction in PD patients with RBD (PD-RBD) and those without and explores their specificity to cognitive domains. Methods: A meta-analysis using a random-effects model was performed for 16 different cognitive domains, including global cognitive function, memory (long-term verbal recall, long-term verbal recognition, long-term visual recall, short-term spatial recall, and short-term verbal recall), executive function (general, fluid reasoning, generativity, shifting, inhibition, and updating), language, processing speed/complex attention/working memory, visuospatial/constructional ability, and psychomotor ability. The cognitive difference between the groups of patients was measured as a standardized mean difference (SMD, Cohen's d). PD-RBD patients were classified into Confirmed-RBD (definite diagnosis with polysomnography, PSG) and Probable-RBD (without PSG re-confirmation). In some domains, RBD patients could not be analyzed separately due to the exiguity of primary studies; this analysis refers to such RBD patients as "Mixed-RBD." Results: Thirty-nine studies with 6,695 PD subjects were finally included. Confirmed-RBD patients showed worse performance than those without in global cognitive function, long-term verbal recall, long-term verbal recognition, generativity, inhibition, shifting, language, and visuospatial/constructional ability; Probable-RBD, in global cognitive function and shifting; and Mixed-RBD, in long-term visual recall, Mao et al. RBD and Cognition in PD? short-term spatial recall, general executive function, and processing speed/complex attention/working memory. Conclusion: This meta-analysis strongly suggests a relationship between RBD, Confirmed-RBD in particular, and cognitive dysfunctions in PD patients. Early and routine screening by sensitive and targeted cognitive tasks is necessary for all PD-RBD patients because it may offer the therapeutic time window before they evolve to irreversible dementia.

Body-First Subtype of Parkinson’s Disease with Probable REM-Sleep Behavior Disorder Is Associated with Non-Motor Dominant Phenotype

“…Although we assessed RBD via a screening questionnaire, our results were consistent with a prior study using PSG-proven RBD, which indicated an association of a non-motor dominant phenotype in PD with PSG-proven RBD [ 4 ]. However, we observed only a trend in the negative effect of pRBD on global cognitive performance in PD, which did not correspond to several cross-sectional and longitudinal studies [ 8 ]. To assess a potential independent variable influencing cognitive performance, we identified a protective effect of YoE on cognitive decline in the overall PD group, but we did not identify a significant difference in pRBD PD vs. non-pRBD PD in terms of YoE or TLS.…”

“…sectional and longitudinal studies[8]. To assess a269 potential independent variable influencing cognitive 270 performance, we identified a protective effect of YoE 271 on cognitive decline in the overall PD group, but we 272 did not identify a significant difference in pRBD PD 273 vs. non-pRBD PD in terms of YoE or TLS.…”

“…On the one hand, we observe an overall consensus regarding a non-motor dominant profile of PD with higher autonomic dysfunction and more rapid cognitive decline. On the other hand, prior studies have reported contradictory findings on the effect of comorbid RBD on motor progression in PD [5][6][7][8]. Moreover, genetic risk factors and PD-causing rare mutations with a substantial effect on the clinical phenotype were rarely systematically addressed in the context of concomitant RBD and PD and their effect on the severity of the clinical phenotype.…”

Application of the Chinese Version of the Montreal Cognitive Assessment-Basic for Assessing Mild Cognitive Impairment in Parkinson’s Disease

“…When combining the effects of age and the severity of extrapyramidal signs, risk of incident dementia in PD was significantly increased [ 26 ]. In addition to motor symptoms, we also found that one non-motor symptom, RBD, was closely related to MCI in PD, which was also in line with previous cross-sectional and longitudinal studies [ 28 ]. Natalia Jozwiak et al found that PD patients with RBD had poorer performance on cognitive tests measuring attention, executive functions, language, memory and visuospatial abilities [ 29 ].…”

Pharmacological and Non-pharmacological Treatments of Sleep Disorders in Parkinson's Disease

“…In addition, PD patients with co-existent RBD are characterized by older ages, male, younger ages of PD onset, akinetic/rigid phenotype, falls, higher disease severity, longer disease duration, greater motor fluctuations, and higher levodopa dose [ 21 , 103 ]. Meta-analysis also strongly suggests a relationship between RBD and cognitive impairment, making it a sign of worsening condition in PD patients [ 104 ].…”