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

Max J Oosterwegel; Jesse H Krijthe; Melina G H E den Brok; Lieneke van den Heuvel; Edo Richard; Tom Heskes; Bastiaan R Bloem; Luc J W Evers

doi:10.3389/fneur.2023.1138546

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

Front Neurol. 2023 Apr 12:14:1138546. doi: 10.3389/fneur.2023.1138546. eCollection 2023.

Authors

Max J Oosterwegel^{1

2}, Jesse H Krijthe³, Melina G H E den Brok^{4

5}, Lieneke van den Heuvel¹, Edo Richard^{4

5}, Tom Heskes², Bastiaan R Bloem¹, Luc J W Evers^{1

2}

Affiliations

¹ Center of Expertise for Parkinson and Movement Disorders, Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.
² Department of Data Science, Institute for Computing and Information Sciences, Radboud University, Nijmegen, Netherlands.
³ Department of Intelligent Systems, Delft University of Technology, Delft, Netherlands.
⁴ Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.
⁵ Department of Neurology, Amsterdam University Medical Center, Location AMC, Amsterdam, Netherlands.

Abstract

Background: Currently 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.

Objectives: We 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.

Methods: We 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.

Results: Mean 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.

Conclusions: Based 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.

Keywords: BMI; Framingham; Parkinson's disease; cardiovascular risk; causal inference; disease modification; hypertension; longitudinal modeling.

Grants and funding

The Center of Expertise for Parkinson & Movement Disorders of the Radboud University Medical Center was supported by a Center of Excellence Grant of the Parkinson's Foundation. This research was funded by a grant from the Netherlands Organization for Scientific Research (TOP Grant #91215076). The Parkinson's Progression Markers Initiative—a public-private partnership—is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners (which can be found at www.ppmi-info.org/about-ppmi/who-we-are/study-sponsors). Data from the Tracking Parkinson's study was obtained from the Critical Path for Parkinson's (CPP) Integrated Parkinson's Database. The CPP Integrated Parkinson's Database initiative is funded by Parkinson's UK and consortium membership organizations and launched in October of 2015 by the Critical Path Institute (C-Path). The investigators within the organizations that contributed data to the CPP Integrated Parkinson's Database assisted with the design and implementation of the data platform and/or provided data but did not participate in the analysis of the data or the writing of this report.