Abstract

Olfactory loss, motor impairment, anxiety/depression, and REM-sleep behaviour disorder (RBD) are prodromal Parkinson’s disease (PD) features. PD risk prediction models typically dichotomize test results and apply likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance classification between PD and controls. PD patient data on smell (UPSIT), possible RBD (RBD Screening Questionnaire), and anxiety/depression (LADS) were taken from the Tracking Parkinson’s study (n = 1046). For motor impairment (BRAIN test) in PD cases, published data were supplemented (n = 87). Control data (HADS for anxiety/depression) were taken from the PREDICT-PD pilot study (n = 1314). UPSIT, RBDSQ, and anxiety/depression data were analysed using logistic regression to determine which items were associated with PD. Gaussian distributions were fitted to BRAIN test scores. LRs were calculated from logistic regression models or score distributions. False-positive rates (FPRs) for specified detection rates (DRs) were calculated. Sixteen odours were associated with PD; LRs for this set ranged from 0.005 to 5511. Six RBDSQ and seven anxiety/depression questions were associated with PD; LRs ranged from 0.35 to 69 and from 0.002 to 402, respectively. BRAIN test LRs ranged from 0.16 to 1311. For a 70% DR, the FPR was 2.4% for the 16 odours, 4.6% for anxiety/depression, 16.0% for the BRAIN test, and 20.0% for the RBDSQ. Specific selections of (prodromal) PD marker features rather than dichotomized marker test results optimize PD classification. Such optimized classification models could improve the ability of algorithms to detect prodromal PD; however, prospective studies are needed to investigate their value for PD-prediction models.

Highlights

  • Parkinson’s disease (PD) affects about 1% of individuals over the age of 60 years[1]

  • For the same 14.9% false-positive statistically significantly associated with PD

  • In comparison to dichotomous likelihood ratios for olfactory performance of 6.4 for those with olfactory loss vs. 0.40 for those with normosmia[7], olfactory likelihood ratios presented here ranged from 0.07 to 45 based on the full range of olfactory performance and ranged from 0.009 to about 5500 using the logistic regression approach that identified 16 odours, which were significantly associated with PD

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Summary

Introduction

Parkinson’s disease (PD) affects about 1% of individuals over the age of 60 years[1]. The Movement Disorders Society (MDS) produced criteria for the diagnosis of prodromal PD6,7, a risk algorithm based upon primary-care presentations has been described[8], as well as risk algorithms based on clinical and genetic classification[9,10]. Most of these algorithms dichotomize exposure variables and risk factors, which in turn can lead to a loss of information if the underlying trait is continuous or discrete[11]

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