Identifying prodromal symptoms at high specificity for Parkinson's disease

Holly Jackson; Judith Anzures-Cabrera; Tanya Simuni; Ronald B Postuma; Kenneth Marek; Gennaro Pagano

doi:10.3389/fnagi.2023.1232387

Identifying prodromal symptoms at high specificity for Parkinson's disease

Front Aging Neurosci. 2023 Sep 22:15:1232387. doi: 10.3389/fnagi.2023.1232387. eCollection 2023.

Authors

Holly Jackson^{1

2}, Judith Anzures-Cabrera¹, Tanya Simuni³, Ronald B Postuma⁴, Kenneth Marek⁵, Gennaro Pagano^{6

7}

Affiliations

¹ Roche Products Ltd, Welwyn Garden City, United Kingdom.
² Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.
³ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
⁴ Department of Neurology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
⁵ Institute for Neurodegenerative Disorders, New Haven, CT, United States.
⁶ Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.
⁷ University of Exeter Medical School, London, United Kingdom.

Abstract

Introduction: To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing PD. This is often difficult because most of the clinical markers are non-specific, common in PD but also common in older adults (e.g., sleep problems).

Objective: We aimed to identify the clinical markers at high specificity for developing PD by comparing individuals with PD or prodromal PD to healthy controls.

Methods: We investigated motor and non-motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 1 and 2 items) in 64 prodromal PD and 422 PD individuals calculating the odds ratios, adjusting for age and gender, for PD and prodromal PD versus 195 healthy controls. Symptoms at high specificity were defined as having an adjusted odds ratio ≥ 6.

Results: Constipation had an adjusted odds ratio, 6.14 [95% CI: 2.94-12.80] showing high specificity for prodromal PD, and speech difficulties had an adjusted odds ratio, 9.61 [95% CI: 7.88-48.81] showing high specificity for PD. The proportion of participants showing these specific markers was moderate (e.g., prevalence of constipation was 43.75% in prodromal PD, and speech difficulties was 33.89% in PD), suggesting these symptoms may make robust predictors of prodromal PD and PD, respectively.

Discussion: Clinical markers at high specificity for developing PD could be used as tools in the screening of general populations to identify individuals at higher risk of developing PD.

Keywords: Parkinson’s disease; observational study; prevalence; prodromal symptoms; specificity.

Grants and funding

This study received funding from F. Hoffmann-La Roche Ltd. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. All authors declare no other competing interests.