Abstract
The MDS Research Criteria for Prodromal PD allow the diagnosis of prodromal Parkinson's disease using an evidence-based conceptual framework, which was designed to be updated as new evidence becomes available. New prospective evidence of predictive values of risk and prodromal markers published since 2015 was reviewed and integrated into the criteria. Many of the predictive values (likelihood ratios, LR) remain unchanged. The positive likelihood ratio notably increase for olfactory loss and decreased for substantia nigra hyperechogenicity. Negative likelihood ratio remained largely unchanged for all markers. New levels of diagnostic certainty for neurogenic and symptomatic orthostatic hypotension have been added, which substantially differ in positive likelihood ratio from the original publication. For intermediate strength genetic variants, their age-related penetrance is now incorporated in the calculation of the positive likelihood ratio. Moreover, apart from prospective studies, evidence from cross-sectional case-control genome-wide association studies is also considered (given their likely lack of confounding and reverse causation), and to account for the effect of multiple low-penetrance genetic variants polygenic risk scores are added to the model. Diabetes, global cognitive deficit, physical inactivity, and low plasma urate levels in men enter the criteria as new markers. A web-based prodromal PD risk calculator allows the calculation of probabilities of prodromal PD for individuals. Several promising candidate markers may improve the diagnostic accuracy of prodromal PD in the future. © 2019 International Parkinson and Movement Disorder Society.
Highlights
Physical activity is associated with a lower risk for PD in a recent meta-analysis[18] of 8 prospective studies.[19,20,21,22,23,24,25]
Comprehensive time- and cost-efficient self-report tools should be established for large-scale screening for prodromal PD
Specific pharmacological medical treatments have been associated with PD risk, for example, ibuprofen,[50] urate-lowering medication,[51] asthma treatment (β2-adrenoreceptor agonists),[52] betablockers (β2-adrenoreceptor antagonists),[52] and statins.[53]
Summary
Technological advances in wearable or smartphone-based sensor technologies have been considerable. Such objective markers might be predictive as well as sensitive to subtle progressive prodromal changes. Sensor-based quantitative motor[40,41] and nonmotor markers (eg, cardiac/ autonomous dysfunction) in (prodromal) PD41-43 require further prospective evidence and standardization of methods
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