An altered immune response has been identified as a pathophysiological factor in Parkinson’s disease (PD). We aimed to identify blood immunity-associated proteins that discriminate PD from controls... Show moreAn altered immune response has been identified as a pathophysiological factor in Parkinson’s disease (PD). We aimed to identify blood immunity-associated proteins that discriminate PD from controls and that are associated with long-term disease severity in PD patients. Immune response-derived proteins in blood plasma were measured using Proximity Extension Technology by OLINK in a cohort of PD patients (N = 66) and age-matched healthy controls (N = 52). In a selection of 30 PD patients, we evaluated changes in protein levels 7–10 years after the baseline and assessed correlations with motor and cognitive assessments. Data from the Parkinson’s Disease Biomarkers Program (PDBP) cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort were used for independent validation. PD patients showed an altered immune response compared to controls based on a panel of four proteins (IL-12B, OPG, CXCL11, and CSF-1). The expression levels of five inflammation-associated proteins (CCL23, CCL25, TNFRSF9, TGF-alpha, and VEGFA) increased over time in PD and were partially associated with more severe motor and cognitive symptoms at follow-up. Increased CCL23 levels were associated with cognitive decline and the APOE4 genotype. Our findings provide further evidence for an altered immune response in PD that is associated with disease severity in PD over a long period of time. Show less
Background The most common genetic risk factor for Parkinson's disease known is a damaging variant in theGBA1gene. The entireGBA1gene has rarely been studied in a large cohort from a single... Show moreBackground The most common genetic risk factor for Parkinson's disease known is a damaging variant in theGBA1gene. The entireGBA1gene has rarely been studied in a large cohort from a single population. The objective of this study was to assess the entireGBA1gene in Parkinson's disease from a single large population. Methods TheGBA1gene was assessed in 3402 Dutch Parkinson's disease patients using next-generation sequencing. Frequencies were compared with Dutch controls (n = 655). Family history of Parkinson's disease was compared in carriers and noncarriers. Results Fifteen percent of patients had aGBA1nonsynonymous variant (including missense, frameshift, and recombinant alleles), compared with 6.4% of controls (OR, 2.6;P < 0.001). Eighteen novel variants were detected. Variants previously associated with Gaucher's disease were identified in 5.0% of patients compared with 1.5% of controls (OR, 3.4;P < 0.001). The rarely reported complex allele p.D140H + p.E326K appears to likely be a Dutch founder variant, found in 2.4% of patients and 0.9% of controls (OR, 2.7;P= 0.012). The number of first-degree relatives (excluding children) with Parkinson's disease was higher in p.D140H + p.E326K carriers (5.6%, 21 of 376) compared with p.E326K carriers (2.9%, 29 of 1014); OR, 2.0;P= 0.022, suggestive of a dose effect for differentGBA1variants. Conclusions Dutch Parkinson's disease patients display one of the largest frequencies ofGBA1variants reported so far, consisting in large part of the mild p.E326K variant and the more severe Dutch p.D140H + p.E326K founder allele. (c) 2020 International Parkinson and Movement Disorder Society Show less
Background Many patients with Parkinson's disease are treated with physiotherapy. We have developed a community-based professional network (ParkinsonNet) that involves training of a selected number... Show moreBackground Many patients with Parkinson's disease are treated with physiotherapy. We have developed a community-based professional network (ParkinsonNet) that involves training of a selected number of expert physiotherapists to work according to evidence-based recommendations, and structured referrals to these trained physiotherapists to increase the numbers of patients they treat. We aimed to assess the efficacy of this approach for improving health-care outcomes. Methods Between February, 2005, and August, 2007, we did a cluster-randomised trial with 16 clusters (defined as community hospitals and their catchment area). Clusters were randomly allocated by use of a variance minimisation algorithm to ParkinsonNet care (n=8) or usual care (n=8). Patients were assessed at baseline and at 8, 16, and 24 weeks of follow-up. The primary outcome was a patient preference disability score, the patient-specific index score, at 16 weeks. Health secondary outcomes were functional mobility, mobility-related quality of life, and total societal costs over 24 weeks. Analysis was by intention to treat. This trial is registered, number NCT00330694. Findings We included 699 patients. Baseline characteristics of the patients were comparable between the ParkinsonNet clusters (n=358) and usual-care clusters (n=341). The primary endpoint was similar for patients within the ParkinsonNet clusters (mean 47.7, SD 21.9) and control clusters (48.3, 22.4). Health secondary endpoints were also similar for patients in both study groups. Total costs over 24 weeks were lower in ParkinsonNet clusters compared with usual-care clusters (difference (sic)727; 95% CI 56-1399). Interpretation Implementation of ParkinsonNet networks did not change health outcomes for patients living in ParkinsonNet clusters. However, health-care costs were reduced in ParkinsonNet clusters compared with usual-care clusters. Show less
