2 research outputs found
Extensive validation study of the Parkinson's Disease Composite Scale
Background and purpose A composite instrument able to rapidly and
reliably assess the most relevant motor and non-motor afflictions
suffered by Parkinson’s disease (PD) patients in a real world clinic
setting is an unmet need. The recently validated PD Composite Scale
(PDCS) was designed to fulfil this gap as a quick, comprehensive PD
assessment. The objective of this study was extensive evaluation of the
PDCS’s clinimetric properties using a large international sample.
Methods This was a cross-sectional study in which the PDCS, the Movement
Disorder Society Unified Parkinson’s Disease Rating Scale and the
Clinical Impression of Severity Index for PD were applied. Basic
clinimetric attributes of the PDCS were analysed. Results In total, 776
PD patients were included. The PDCS total score showed negligible floor
and ceiling effects. Three factors (54.5% of the variance) were
identified: factor 1 included motor impairment, fluctuations and
disability; factor 2, non-motor symptoms; and factor 3, tremor and
complications of therapy. Cronbach’s alpha was from 0.66 to 0.79.
Inter-rater reliability showed weighted kappa values from 0.79 to 0.98
for items and intraclass correlation coefficient values from 0.95
(Disability) to 0.99 (Motor and total score). The Bland-Altmann method,
however, showed irregular concordance. PDCS standard error of
measurement and convergent validity with equivalent constructs of other
measures were satisfactory (>= 0.70). PDCS scores significantly differed
by Hoehn and Yahr stage. Conclusion Overall, in line with previous
findings, the PDCS is a feasible, acceptable, valid, reliable and
precise instrument for quickly and comprehensively assessing PD
patients
Moving beyond neurons:the role of cell type-specific gene regulation in Parkinson’s disease heritability
Abstract
Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types