11 research outputs found
The evolution of diagnosis from symptom onset to death in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) compared to Parkinson's disease (PD)
Funding Dr Swallow received a clinical research fellowship jointly funded by the Chief Scientist Office (CSO) of the Scottish Government and PSP Association. The PINE study is funded by Parkinsonās UK, the Scottish Chief Scientist Office, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, NHS Grampian endowments and SPRING.Peer reviewedPublisher PD
Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease
Funded by Parkinson's UK National Institute for Health Research (NIHR) DeNDRoN network NIHR Newcastle Biomedical Research Unit Newcastle University NIHR funded Biomedical Research Centre in CambridgePeer reviewedPublisher PD
Variation in Recent Onset Parkinson's Disease : Implications for Prodromal Detection
The research was funded by Parkinsonās UK and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge.Peer reviewedPublisher PD
Statins are underused in recent-onset Parkinson's disease with increased vascular risk: findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts
Background Cardiovascular disease (CVD) influences
phenotypic variation in Parkinsonās disease (PD), and is
usually an indication for statin therapy. It is less clear
whether cardiovascular risk factors influence PD
phenotype, and if statins are prescribed appropriately.
Objectives To quantify vascular risk and statin use in
recent-onset PD, and examine the relationship between
vascular risk, PD severity and phenotype.
Methods Cardiovascular risk was quantified using the
QRISK2 calculator (high ā„20%, medium ā„10 and
<20%, low risk <10%). Motor severity and phenotype
were assessed using the Movement Disorder Society
Unified PD Rating Scale (UPDRS) and cognition by the
Montreal cognitive assessment.
Results In 2909 individuals with recent-onset PD, the
mean age was 67.5 years (SD 9.3), 63.5% were men
and the mean disease duration was 1.3 years (SD 0.9).
33.8% of cases had high vascular risk, 28.7% medium
risk, and 22.3% low risk, while 15.2% of cases had
established CVD. Increasing vascular risk and CVD were
associated with older age ( p<0.001), worse motor score
(p<0.001), more cognitive impairment (p<0.001) and
worse motor phenotype ( p=0.021). Statins were
prescribed in 37.2% with high vascular risk, 15.1% with
medium vascular risk and 6.5% with low vascular risk,
which compared with statin usage in 75.3% of those
with CVD.
Conclusions Over 60% of recent-onset PD patients
have high or medium cardiovascular risk (meriting statin
usage), which is associated with a worse motor and
cognitive phenotype. Statins are underused in these
patients, compared with those with vascular disease,
which is a missed opportunity for preventive treatment
The evolution of diagnosis from symptom onset to death in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) compared to Parkinsonās disease (PD)
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Genetic analysis of Mendelian mutations in a large UK population-based Parkinson's disease study.
Our objective was to define the prevalence and clinical features of genetic Parkinson's disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features. Of the 2262 participants recruited to the Tracking Parkinson's study, 424 had young-onset Parkinson's disease (age at onset ā¤ 50) and 1799 had late onset Parkinson's disease. A range of methods were used to genotype 2005 patients: 302 young-onset patients were fully genotyped with multiplex ligation-dependent probe amplification and either Sanger and/or exome sequencing; and 1701 late-onset patients were genotyped with the LRRK2 'Kompetitive' allele-specific polymerase chain reaction assay and/or exome sequencing (two patients had missing age at onset). We identified 29 (1.4%) patients carrying pathogenic mutations. Eighteen patients carried the G2019S or R1441C mutations in LRRK2, and one patient carried a heterozygous duplication in SNCA. In PRKN, we identified patients carrying deletions of exons 1, 4 and 5, and P113Xfs, R275W, G430D and R33X. In PINK1, two patients carried deletions in exon 1 and 5, and the W90Xfs point mutation. Eighteen per cent of patients with age at onset ā¤30 and 7.4% of patients from large dominant families carried pathogenic Mendelian gene mutations. Of all young-onset patients, 10 (3.3%) carried biallelic mutations in PRKN or PINK1. Across the whole cohort, 18 patients (0.9%) carried pathogenic LRRK2 mutations and one (0.05%) carried an SNCA duplication. There is a significant burden of LRRK2 G2019S in patients with both apparently sporadic and familial disease. In young-onset patients, dominant and recessive mutations were equally common. There were no differences in clinical features between LRRK2 carriers and non-carriers. However, we did find that PRKN and PINK1 mutation carriers have distinctive clinical features compared to young-onset non-carriers, with more postural symptoms at diagnosis and less cognitive impairment, after adjusting for age and disease duration. This supports the idea that there is a distinct clinical profile of PRKN and PINK1-related Parkinson's disease. We estimate that there are approaching 1000 patients with a known genetic aetiology in the UK Parkinson's disease population. A small but significant number of patients carry causal variants in LRRK2, SNCA, PRKN and PINK1 that could potentially be targeted by new therapies, such as LRRK2 inhibitors.Only competing interests included in the manuscript