BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) is one of the most specific prodromal indicators for Parkinson's disease (PD).ObjectivesTo test the validity of the RBD‐Screening Questionnaire (RBDSQ) in assessing RBD in early PD.MethodsThe RBDSQ was completed before video‐supported polysomnography (vPSG) by 134 de novo PD patients, 109 matched controls without neurological disorder (CTR) and 30 subjects with idiopathic RBD (iRBD) without clinical signs of PD; results were compared with vPSG‐confirmed RBD diagnosis.Results and ConclusionsSensitivity/specificity of the RBDSQ for the PD cohort were 0.44/0.84 at the previously published cut‐off score of 6 for PD patients, and the area under the curve (AUC) 0.68 (95% CI, 0.56–0.79). By contrast, in the iRBD/CTR cohort the RBDSQ (cut‐off = 5) had a sensitivity/specificity of 0.97/0.84 and an AUC of 0.95 (95% CI, 0.90–1.00). Subanalysis of question 6 only (4 subitems asking for dream enactment) at a cut‐off score of 1 revealed a sensitivity of 0.74 and a specificity of 0.70 for the de novo PD cohort, AUC was 0.74 (95% CI, 0.63–0.84). RBDSQ is an insufficient screening tool for RBD in de novo PD. New screening tools for RBD assessment need to be developed.
Advanced age represents one of the major risk factors for Parkinson’s Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson’s Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson’s Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson’s Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson’s Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson’s Disease patients, and healthy siblings of Parkinson’s Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson’s Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson’s Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson’s Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson’s Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson’s Disease.
A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had <1% probability of having prodromal PD; 100 between 1 and 10%, 26 siblings between 10 and 80%, one fulfilled the criteria for prodromal PD. According to the current analysis, we cannot confirm the increased risk of PD siblings for prodromal PD. Siblings showed a heterogeneous distribution of prodromal PD markers and probability. Additional parameters, including strong disease markers, should be investigated to verify if these results depend on validity and sensitivity of prodromal PD criteria, or if siblings’ risk is not elevated.
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