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

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, 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.