Data_Sheet_1_The effect of cardiovascular risk on disease progression in de novo Parkinson's disease patients: An observational analysis.DOCX

BackgroundCurrently available treatment options for Parkinson's disease are symptomatic and do not alter the course of the disease. Recent studies have raised the possibility that cardiovascular risk management may slow the progression of the disease.ObjectivesWe estimated the effect of baseline cardiovascular risk factors on the progression of Parkinson's disease, using measures for PD-specific motor signs and cognitive functions.MethodsWe used data from 424 de novo Parkinson's disease patients and 199 age-matched controls from the observational, multicenter Parkinson's Progression Markers Initiative (PPMI) study, which included follow-up of up to 9 years. The primary outcome was the severity of PD-specific motor signs, assessed with the MDS-UPDRS part III in the “OFF”-state. The secondary outcome was cognitive function, measured with the Montreal Cognitive Assessment, Symbol Digit Modalities Test, and Letter-Number Sequencing task. Exposures of interest were diabetes mellitus, hypertension, body mass index, cardiovascular event history and hypercholesterolemia, and a modified Framingham risk score, measured at baseline. The effect of each of these exposures on disease progression was modeled using linear mixed models, including adjustment for identified confounders. A secondary analysis on the Tracking Parkinson's cohort including 1,841 patients was performed to validate our findings in an independent patient cohort.ResultsMean age was 61.4 years, and the average follow-up was 5.5 years. We found no statistically significant effect of any individual cardiovascular risk factor on the MDS-UPDRS part III progression (all 95% confidence intervals (CIs) included zero), with one exception: in the PD group, the estimated effect of a one-point increase in body mass index was 0.059 points on the MDS-UPDRS part III per year (95% CI: 0.017 to 0.102). We found no evidence for an effect of any of the exposures on the rate of change in cognitive functioning in the PD group. Similar results were observed for the Tracking Parkinson's cohort (all 95% CIs overlapped with PPMI), but the 95% CI of the effect of body mass index on the MDS-UPDRS part III progression included zero.ConclusionsBased on this analysis of two large cohorts of de novo PD patients, we found no evidence to support clinically relevant effects of cardiovascular risk factors on the clinical progression of Parkinson's disease.</p

Additional file 1: of Modifiable dementia risk score to study heterogeneity in treatment effect of a dementia prevention trial: a post hoc analysis in the preDIVA trial using the LIBRA index

Figure S1. Flow diagram. Table S1. Baseline characteristics per randomisation group and LIBRA group. Table S2. Secondary analyses. Table S3. Competing risk analysis. Table S4. Subgroup analyses on age, hypertension grade, antihypertensive medication, history of cardiovascular disease and diabetes. Table S5. Treatment effect on vascular risk factors in LIBRA groups. Table S6. Baseline characteristics of participants included in and excluded from cognitive analyses. Table S7. Treatment effect on cognition in LIBRA groups (DOCX 533 kb

Dementia incidence trend over 1992-2014 in the Netherlands: Analysis of primary care data

<div><p>Background</p><p>Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands.</p><p>Methods and findings</p><p>A dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRNs) across the country. Data regarding dementia incidence were obtained using general-practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 y and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people for the years 1992 to 2014, corresponding to over 4 million person-years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95% CI 0.5% to 3.8%), and incidence rates were 1.08 (95% CI 1.04 to 1.13) times higher for women compared to men. Despite their relatively low numbers of person-years, the highest age groups contributed most to the increasing trend. There was no significant overall change in incidence rates since the start of a national dementia program in 2003 (−0.025; 95% CI −0.062 to 0.011). Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis by general practitioners in electronic health records, and needs to be taken into account when interpreting the data.</p><p>Conclusions</p><p>Within the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate a dramatic absolute increase in dementia occurrence over the years to come.</p></div

Dementia incidence rate by age group.

<p>Observed (circles) and estimated (lines) dementia incidence rate per 1,000 person-years (py) by age group for men (solid black circles and lines) and women (open red circles, dashed lines). The sizes of the circles indicate the number of general practitioner registration networks that provided data for the respective years.</p

Characteristics of the Dutch general practice registration networks included in this study.

<p>Characteristics of the Dutch general practice registration networks included in this study.</p

Absolute number of person-years at risk and incident dementia cases per calendar year (logarithmic <i>y</i>-axis).

<p>Absolute number of person-years at risk and incident dementia cases per calendar year (logarithmic <i>y</i>-axis).</p

Variation in trends between general practitioner registration networks as estimated using model 1.

<p>Variation in trends between general practitioner registration networks as estimated using model 1.</p

Results of negative binomial regression analysis, giving incidence rate ratios of change in dementia incidence.

<p>Results of negative binomial regression analysis, giving incidence rate ratios of change in dementia incidence.</p