Considerations in the Use of MDS Research Criteria for Prodromal Parkinson’s in Rapid Eye Movement Sleep Behaviour Disorder and Population Cohorts

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We welcome the remarks of Mahlknecht and colleagues regarding the practical application of the MDS research criteria for prodromal Parkinson’s disease (PD). Before commenting further on our own use of these, it is worth revisiting how and why these criteria were established.

The MDS criteria were devised as a data-driven, objective method of estimating an individual’s absolute probability of being in the prodromal phase of PD¹ by incorporating a range of risk factors and prodromal markers. The weighting assigned to each variable is determined solely from the evidence of its predictive value. The criteria can be used with as much or as little data as one has available; the accuracy will improve the more variables are included. Importantly, the purpose is to estimate whether prodromal neurodegeneration is present, not when an individual will convert to PD.

In light of this, it is clear that in a cohort with polysomnographically proven rapid eye movement sleep behaviour disorder (RBD), we would expect ≥75% of patients to fulfill these criteria, given the known long-term risk in this population.^2–4 The high likelihood ratio (LR) attributed to RBD reflects this and, as acknowledged in our original discussion,⁵ the high probabilities seen in RBD cohorts are largely accounted for by the presence of RBD itself. We agree that many of the other risk factors have a negligible effect in comparison, but we do not consider this a weakness of the criteria per se, as it simply reflects the clinical reality.