Dataset Information

Mortality of People with Parkinson's Disease in a Large UK-Based Cohort Study: Time Trends and Relationship to Disease Duration.

ABSTRACT:

Background

Parkinson's disease (PD) is associated with increased mortality, but little is known about changes over time, and relationship to disease progression.

Objectives

To explore how PD mortality rates have changed over time and their relationship to disease duration and demographics using a large population-based cohort in the UK.

Methods

We included individuals aged 50+ years with a first recording of PD diagnosis and at least two prescriptions of any antiparkinsonian drug actively registered within a general practice from 2006 to 2016 and up to six frequency-matched controls from The Health Improvement Network (THIN) database. We estimated adjusted mortality rates using multivariable Poisson regression.

Results

A total of 10,104 people with a diagnosis of PD and 55,664 people without PD were included. Overall, PD was associated with slightly increased mortality compared to non-PD controls (adjusted mortality rate ratio: 1.14; 95% CI: 1.03 to 1.19). Adjusted mortality rates per 1000 person-years at risk for people with PD approximately doubled in the 5 years following diagnosis from 43 (95% CI: 38 to 48) to 75 (95% CI: 64 to 85). Following adjustments for age, gender, and time since diagnosis, mortality rates between 2007 and 2016 declined more slowly for people with PD (2% per year; 95% CI: 0%-4%) compared to people without PD (5% per year; 95% CI: 3%-6%).

Conclusions

Whilst mortality in PD is only slightly increased overall, it gradually increases with advancing disease. There has been a decline in mortality in PD over time, but this decrease was less pronounced than that in the general population. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

SUBMITTER: Okunoye O

PROVIDER: S-EPMC7612920 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Mortality of People with Parkinson's Disease in a Large UK-Based Cohort Study: Time Trends and Relationship to Disease Duration.

Okunoye Olaitan O Horsfall Laura L Marston Louise L Walters Kate K Schrag Anette A

Movement disorders : official journal of the Movement Disorder Society 20210805 12

<h4>Background</h4>Parkinson's disease (PD) is associated with increased mortality, but little is known about changes over time, and relationship to disease progression.<h4>Objectives</h4>To explore how PD mortality rates have changed over time and their relationship to disease duration and demographics using a large population-based cohort in the UK.<h4>Methods</h4>We included individuals aged 50+ years with a first recording of PD diagnosis and at least two prescriptions of any antiparkinsonia ...[more]

PMID: 34351000

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Project description: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 ≤ 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 ≤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.

Project description:BackgroundShort or long sleep duration is proposed as a potential risk factor for all-cause mortality in the older people, yet the results of published studies are not often reproducible.MethodsLiterature retrieval, study selection and data extraction were completed independently and in duplicate. Only prospective cohort studies were included. Effect-size estimates are expressed as hazard ratio (HR) and 95% confidence interval (CI).ResultsSummary data from 28 articles, involving a total of 95,259 older people, were meta-analyzed. Overall analyses revealed a remarkably significant association between long sleep duration and all-cause mortality (adjusted HR = 1.24, 95% CI: 1.16-1.33, P < .001), whereas only marginal significance was observed for short sleep duration (adjusted HR = 1.04; 95% CI: 1.00-1.09; P = .033). Funnel plots suggested no publication bias for short sleep duration (P = .392). The probability of publication bias was high for long sleep duration (P = .020), yet the trim-and-fill method strengthened its significance in predicting all-cause mortality. In subgroup analyses, the association of long sleep duration with all-cause mortality was statistically significant in both women (HR = 1.48; 95% CI: 1.18-1.86; P = .001) and men (HR = 1.31; 95% CI: 1.10-1.58; P = .003). By contrast, with regard to short sleep duration, statistical significance was observed in men (HR = 1.13; 95% CI: 1.04-1.24; P = .007), but not in women (HR = 1.00; 95% CI: 0.85-1.18; P = .999) (Two-sample Z test P = .099). Besides gender, geographic region, sleep survey method, baseline age and follow-up interval were identified as possible causes of between-study heterogeneity in subgroup analyses. Further dose-response regression analyses revealed that trend estimation was more obvious for long sleep duration (regression coefficient: 0.13; P < .001) than for short sleep duration (regression coefficient: 0.02; P = .046).ConclusionsOur findings indicate a significantly increased risk of all-cause mortality associated with long sleep duration, especially in women, as well as with short sleep duration in men only.

Dataset Information

Mortality of People with Parkinson's Disease in a Large UK-Based Cohort Study: Time Trends and Relationship to Disease Duration.

Background

Objectives

Methods

Results

Conclusions

Publications

Mortality of People with Parkinson's Disease in a Large UK-Based Cohort Study: Time Trends and Relationship to Disease Duration.

Similar Datasets

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