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Development and Validation of a Prognostic Model for Cognitive Impairment in Parkinson's Disease With REM Sleep Behavior Disorder.

ABSTRACT: The presentation and progression of Parkinson's disease (PD) are not uniform, but the presence of rapid eye movement sleep behavior disorder (RBD) in PD patients may indicate a worse prognosis than isolated PD. Increasing evidence suggests that patients with comorbid PD and RBD (PD-RBD) are more likely to develop cognitive impairment (CI) than those with isolated PD; however, the predictors of CI in PD-RBD patients are not well understood. This study aimed to develop a prognostic model for predicting mild cognitive impairment (MCI) in PD-RBD patients. The data of PD-RBD patients were extracted from the Parkinson's Progression Markers Initiative study (PPMI), and the sample was randomly divided into a training set (n = 96) and a validation set (n = 24). PD-MCI as defined by the level II Movement Disorder Society (MDS) diagnostic criteria was the outcome of interest. The demographic features, clinical assessments, dopamine transporter (DAT) imaging data, cerebrospinal fluid (CSF) analyses and genetic data of PD patients were considered candidate predictors. We found that performance on the University of Pennsylvania Smell Identification Test (UPSIT), the mean signal and asymmetry index of the putamen on DAT imaging, p-tau/α-syn and p-tau in CSF, and rs55785911 genotype were predictors of PD-MCI in PD-RBD patients. A C-index of 0.81 was obtained with this model, and a C-index of 0.73 was obtained in the validation set. Favorable results of calibrations and decision curve analysis demonstrated the efficacy and feasibility of this model. In conclusion, we developed a prognostic model for predicting MCI in PD-RBD patients; the model displayed good discrimination and calibration and may be a convenient tool for clinical application. Larger samples and external validation sets are needed to validate this model.

SUBMITTER: Chen F

PROVIDER: S-EPMC8311737 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundResting-state functional MRI has been proposed as a new biomarker of prodromal neurodegenerative disorders, but it has been poorly investigated in the idiopathic form of rapid-eye-movement sleep behavior disorder (IRBD), a clinical harbinger of subsequent synucleinopathy. Particularly, a complex-network approach has not been tested to study brain functional connectivity in IRBD patients.ObjectivesThe aim of the current work is to characterize resting-state functional connectivity in IRBD patients using a complex-network approach and to determine its possible relation to cognitive impairment.MethodTwenty patients with IRBD and 27 matched healthy controls (HC) underwent resting-state functional MRI with a 3T scanner and a comprehensive neuropsychological battery. The functional connectome was studied using threshold-free network-based statistics. Global and local network parameters were calculated based on graph theory and compared between groups. Head motion, age and sex were introduced as covariates in all analyses.ResultsIRBD patients showed reduced cortico-cortical functional connectivity strength in comparison with HC in edges located in posterior regions (p <0.05, FWE corrected). This regional pattern was also shown in an independent analysis comprising posterior areas where a decreased connectivity in 51 edges was found, whereas no significant results were detected when an anterior network was considered (p <0.05, FWE corrected). In the posterior network, the left superior parietal lobule had reduced centrality in IRBD. Functional connectivity strength between left inferior temporal lobe and right superior parietal lobule positively correlated with mental processing speed in IRBD (r = .633; p = .003). No significant correlations were found in the HC group.ConclusionOur findings support the presence of disrupted posterior functional brain connectivity of IRBD patients similar to that found in synucleinopathies. Moreover, connectivity reductions in IRBD were associated with lower performance in mental processing speed domain.

Project description:Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson's disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD.The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure (copy) results.When PD-RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.

Project description:ObjectivesTo develop a polysomnographic video-based scale for rating the severity of REM sleep behavior disorder (RBD), to classify the severity of RBD and to determine the intraindividual variability of RBD in patients with Parkinson disease (PD).MethodsTwenty PD patients identified with RBD were investigated with video-supported polysomnography (PSG). Seventy-three motor behavior events during REM sleep were graded visually and polysomnographically on an event-to-event basis according to categorical location of movements: "0" = no visible movement; "1" = slight movements or jerks "2" = movements involving proximal extremities, including violent behavior; "3" = axial involvement including bed falls. Vocalizations were rated as "1" for present or "0" for absent. Ratings were performed by 2 blinded raters. Reliability was calculated with Cohen's ?. Final RBD severity was determined by the highest score given. This rating scale was then used to compare RBD severity and density, calculated as RBD episodes per REM sleep minute over 2 consecutive nights in 10 additional PD patients with RBD. Statistical significance was determined by effect size (Hedges' g) and calculation of the confidence interval.ResultsInterrater reliability of the scale was 0.8 for movement data and 0.89 for vocalization data. Intraindividual RBD density varied significantly (effect size 0.5 ± 0.22; confidence interval 0.2 to 0.79) by factor 2.5 between the 2 PSG nights. Final RBD severity score differed in 60% of patients between nights 1 and 2. Forty percent of patients showed violent behavior, but only on one night. All patients had severely disturbed sleep with reduced sleep efficiency, loss of slow wave sleep, sleep fragmentation, and an increased periodic limb movement (PLM) index.ConclusionThe RBD severity scale (RBDSS) is a reliable, easy-to-use tool for assessing motor events during REM sleep with PSG. Severity and phenomenology of RBD shows a significant variability in the individual PD patient.

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Development and Validation of a Prognostic Model for Cognitive Impairment in Parkinson's Disease With REM Sleep Behavior Disorder.

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