78 research outputs found
Neurofunctional correlates of attention rehabilitation in Parkinson's disease: an explorative study
The effectiveness of cognitive rehabilitation (CR) in Parkinson's disease (PD) is in its relative infancy, and nowadays there is insufficient information to support evidence-based clinical protocols. This study is aimed at testing a validated therapeutic strategy characterized by intensive computer-based attention-training program tailored to attention deficits. We further investigated the presence of synaptic plasticity by means of functional magnetic resonance imaging (fMRI). Using a randomized controlled study, we enrolled eight PD patients who underwent a CR program (Experimental group) and seven clinically/demographically-matched PD patients who underwent a placebo intervention (Control group). Brain activity was assessed using an 8-min resting state (RS) fMRI acquisition. Independent component analysis and statistical parametric mapping were used to assess the effect of CR on brain function. Significant effects were detected both at a phenotypic and at an intermediate phenotypic level. After CR, the Experimental group, in comparison with the Control group, showed a specific enhanced performance in cognitive performance as assessed by the SDMT and digit span forward. RS fMRI analysis for all networks revealed two significant groups (Experimental vs Control) × time (T0 vs T1) interaction effects on the analysis of the attention (superior parietal cortex) and central executive neural networks (dorsolateral prefrontal cortex). We demonstrated that intensive CR tailored for the impaired abilities impacts neural plasticity and improves some aspects of cognitive deficits of PD patients. The reported neurophysiological and behavioural effects corroborate the benefits of our therapeutic approach, which might have a reliable application in clinical management of cognitive defici
Validation of the Italian version of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale.
Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study
A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies
Validation of the Italian version of the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale
Automatic Detection of White Matter Hyperintensities in Healthy Aging and Pathology Using Magnetic Resonance Imaging: A Review
Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study.
We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)
The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia
Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)
Correction to: s41531-023-00526-9 npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below
Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease
Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations
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