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Despite the increasing global importance of Parkinson's disease (PD), its exact incidence in the general population is not known. Comparing published studies, incidence rates from 1.5 to 19/100 000 person-years have been reported but such differences cannot simply be attributed to between-population differences in PD risk as no two studies have used the same case ascertainment strategy.1 We have previously published the results of a community-based study of incident parkinsonism including PD in Cambridgeshire, UK: CamPaIGN (Cambridgeshire Incidence of PD from GP to Neurologist).2 We now report the findings of a novel second incidence study in the same base population, using the same case ascertainment strategy: PICNICS (Parkinsonism: Incidence and Cognitive and Non-motor heterogeneity In CambridgeShire). This unique undertaking enables us to present a comparative analysis of these studies, representing the most complete set of PD incidence data yet reported in a defined population. The PICNICS study recruited newly diagnosed cases of PD and parkinsonism resident in Cambridgeshire between 1 April 2008 and 31 January 2010. Detailed methods including inclusion and exclusion criteria are available from the author. To summarise, case ascertainment was performed using a service-based screen of the normal routes of UK/National Health Service (NHS) healthcare referral. All general practitioners (GPs) and hospital specialists working with suspected/newly diagnosed PD operating in the county were regularly contacted by mail and electronically throughout the study period. They were instructed to refer all consenting cases …

Background Prognosis in Parkinson9s disease (PD) remains poorly understood due to a lack of unbiased data on the natural history of treated PD. The CamPaIGN study has been the first to prospectively track disease evolution from diagnosis in an unselected population-representative incident cohort. We now report the 10-year follow-up data, focusing on three key irreversible milestones: postural instability (Hoehn and Yahr 3), dementia and death. Methods The cohort was collected between December 2000 and 2002. Those meeting diagnostic criteria (n=142) were followed-up until 1 January 2012. Clinical, neuropsychological and genetic testing were performed. Progression to key milestones was evaluated using Kaplan–Meier and Cox regression survival analyses. Results At 10 years, 55% had died, 68% had postural instability and 46% dementia. 23% had a good outcome at 10 years (surviving free of dementia/postural instability). Death rate was comparable with the UK population (standardised mortality ratio 1.29 (0.97–1.61)). Death certificates indicated PD was a substantial contributor in only 20%, with pneumonia being the commonest cause of death. Age, non-tremor-dominant motor phenotype and comorbidity predicted earlier postural instability. Baseline predictors of dementia were age, motor impairment, ‘posterior-cortical’ cognitive deficits and MAPT genotype. Conclusions (1) outlook in PD is heterogeneous, with most dying or developing dementia or postural instability by 10 years from diagnosis, but a quarter still doing well, with preserved mobility and intact cognition; (2) death is not directly related to PD in the majority; (3) baseline clinical and genetic variables are predictive of outcome and may be helpful in selecting patients for clinical trials.

Background Our understanding of the natural history of idiopathic Parkinson’s disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis. Methods A representative cohort of 132 PD patients was followed from diagnosis for up to 7.9 years (mean 5.2 years). Comprehensive clinical and neuropsychological evaluations were performed every 18 months. Disease progression was evaluated using well validated clinical measures (motor progression and development of dyskinesia on the Unified PD Rating Scale and HoehneYahr scale, dementia onset according to DSM-IV criteria). Multi-level linear modelling was used to chart the nature and rate of progression in parkinsonian symptoms and signs over time. The prognostic importance of baseline demogr‘aphic, clinical and genetic variables was evaluated using survival analysis. Results Axial (gait and postural) symptoms evolve more rapidly than other motor features of PD and appear to be the best index of disease progression. Conversely, conventional outcome measures are relatively insensitive to change over time. Earlier onset of postural instability (HoehneYahr stage 3) is strongly associated with increased age at disease onset and has a significant impact on quality of life. Conclusions Dementia risk is associated with increased age, impaired baseline semantic fluency and the MAPT H1/H1 genotype. The efficacy of disease modifying therapies may be more meaningfully assessed in terms of their effects in delaying the major milestones of PD, such as postural instability and dementia, since it is these that have the greatest impact on patients.

Background Previous studies have failed to agree on the risk factors for excessive daytime sleepiness in Parkinson9s disease and the relative contribution of each as the disease progresses. Methods We studied two community-based incident Parkinson9s disease cohorts. Cohort 1 (n=128) were newly-diagnosed patients and Cohort 2 were assessed at 3.5 years (n=118), 5 years (n=90) and 7 years (n=45) following diagnosis. Using Epworth Sleepiness Scale score as the outcome variable, multivariate linear regression was used to identify risk factors for excessive daytime sleepiness at each assessment. Results Epworth Sleepiness Scale score was significantly lower at diagnosis (Cohort 1) compared to 3.5, 5 and 7 years following diagnosis (Cohort 2). In Cohort 1, the proportion of patients with excessive daytime sleepiness (Epworth Sleepiness Scale score >10) was 20%. In Cohort 2, this rose to 49%, 53% and 44% at 3.5, 5 and 7 years respectively. In the early stages of Parkinson9s disease, a non-tremor dominant motor phenotype, dopamine agonist use and depression were associated with excessive daytime sleepiness, whereas later on, motor disability and impaired quality of life became the most significant factors. Conclusions This is the first study to map the temporal evolution of excessive daytime sleepiness and its risk factors in an incident Parkinson9s disease cohort. We found that hypersomnolence is present throughout the course of the disease and increases with disease progression. The link between non-tremor dominant motor phenotype and excessive daytime sleepiness, but lack of association with cognitive function, implicates brainstem rather than cortex as the principal site of underlying pathology. Dopamine agonists appear to play a contributory role.