Metabolic Brain Networks Associated With Cognition Of REM Sleep Behavior Disorder And The Relationship With Parkinson’s Disease

REM sleep behavior disorder(RBD) is a parasomnia characterized by excessive activity due to loss to normal atonia during REM sleep. Its relationship with neurodegenerative disease has received much attention since its potential role as a biomarker for early diagnosis. It has been documented in many researches to precede or coincide with PD and related disorders. It is estimated that the risk for RBD patient to develop a neurodegenerative disease is about20%in five years, and grow to50%-60%in ten to twelve years. Functional brain networks provide useful information as to the pathophysiology of PD. Using metabolic brain imaging with18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), PD-related metabolic pattern (PDRP) has been established and verified in a number of independent populations.It is proved to be a reliable neuroimaging biomarker for neurodegeneration. Besides, the cognitive function of RBD is of increasing significance. The cognition of PD has been studied widely in the past thirty years. It is now generally accepted that the cognitive impairment in non-demented PD patients includes executive function, visuospatial abilities, language, verbal memory etc. But only a limited number of studies discuss the cognitive function of RBD patients and there is no published data as to the Chinese population.Objective To evaluate the cognitive function in Chinese RBD patients, compare their performance with PD patients in order to find the similarities and differences, and further discuss RBD cognitive profile in association with metabolic brain networks.Methods Group A included fifty RBD patients who were recruited from sleep clinic of Huashan Hospital. All of their diagnosis was confirmed by PSG monitoring. Group B included Fifty PD patients who were recruited from neurology clinic of Huashan Hospital. All of them fulfilled the UK PD Brain Bank Criteria. Group C included fifteen PD patients with chief complaint of sleep symptoms who underwent PSG monitoring and were confirmed of the co-existence of RBD.Group D included fifty normal people with matched demographic information as normal controls. Among the participants in Group A, twenty-eight signed consent forms and were scanned with FDG PET. Their images were processed using Statistical Parametric Mapping (SPM). Based on principal components analysis (PCA), we quantified the expression of PDRP and divided the participants into Group A1(RBD patients with normal PDRP) and Group A2(RBD patients with abnormal PDRP).All of the above mentioned participants underwent a comprehensive neuropsychological evaluation. Mini-mental state examination (MMSE) was first conducted to examine their overall cognitive status, then five main cognitive domain were evaluated in details, including verbal memory, non-verbal memory, visuospatial function, language and attention/executive function.ResultsUsing one-way analysis of variance(ANOVA), between group differences were found in tests including Rey Auditory Verbal Learning Test (RAVLT)-recognition, Rey-Osterrieth complex figure (Rey) copy (time and score), Verbal Fluency, Symbol Digit Modality Test (SDMT), Stroop test (time) and Trail Making Test (TMT).Post-hoc analysis revealed that the performance of RBD patients was lower compared to control subjects in SDMT. PD patients performed poorer than control subjects in Rey-copy (score), Boston Naming Test (BNT), Verbal Fluency-cities, TMT-A, SDMT. The performance of patients with PD-RBD was the poorest compared to patients with PD-NRBD and control subjects in Rey-copy (time), Stroop test (time) and TMT-B.As for RBD patients who underwent PET scan and were divided into Group Al and Group A2, their cognitive performance was also compared with other three groups. Using ANOVA, tests which showed between-group differences included MMSE, RVLT-recognition, Rey-copy (time and score), Verbal Fluency, SDMT, Stroop (time) and TMT.Post-hoc analysis revealed that RBD patients with abnormal PDRP performed poorer than RBD patients with normal PDRP in MMSE. PD patients performed poorer than RBD patients with normal PDRP in Rey-copy (score), but similar to RBD patients with abnormal PDRP. The performance of PD-RBD patients was the poorest compared to others but somehow similar to RBD patients with abnormal PDRP in TMT.ConclusionNon-demented PD patients showed cognitive impairment in visuospatial function, language and attention/executive function. As for RBD patients, the most prominent cognitive impairment centered on attention/executive function. PD patients with RBD performed the worst among all the participants, suggesting the role that RBD plays as an important risk factor for cognitive impairment in PD. Neuropsychological evaluation of RBD in association with brain metabolic network analysis could be the biomarker for early identification of neurodegeneration, but prolonged long-term follow up will be needed in order to verify the true significance of cognitive deficits.