MDS prodromal criteria

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Daniela Berg, Ronald Postuma and the International Parkinson and Movement Disorder Society (MDS) Task Force (20 authors, 2015). Update by Susanne Heinzel, Berg, Thomas Gasser, Honglei Chen, Chen Yao, Postuma and the Task Force (2019). Funders not recorded here.

What happened

The MDS clinical criteria (landmark 167) need visible motor parkinsonism. The prodromal criteria cover the years before that.

• Method. A Bayesian calculation starts from the chance of disease at a given age, then multiplies in likelihood ratios for each risk factor and early marker, such as loss of smell, constipation, polysomnography-confirmed REM sleep behaviour disorder (landmark 221), dopamine-transporter imaging and some genetic variants. "Probable prodromal PD" means 80% or higher. Only markers with prospective evidence of predicting clinical PD were allowed. They are for research, not for telling people they have the disease. (Mov Disord 30:1600–1611, DOI 10.1002/mds.26431.)
• 2019 update. Likelihood ratios were revised. Olfactory loss counts for more; substantia nigra ultrasound for less. New levels of certainty were added for orthostatic hypotension. Diabetes, global cognitive deficit, physical inactivity and (in men) low plasma urate were added as markers. Polygenic risk scores (landmark 333) and genome-wide association data entered the model. A web risk calculator was released. (Mov Disord 34:1464–1470, DOI 10.1002/mds.27802.)

Why it moved us toward a cure

It defines the target population for prevention trials in a way other groups can copy, and it builds on the formal clinical definition (landmark 167) and iRBD cohorts (landmark 221). Without a defined pre-motor group, a slowing drug cannot be tested early.

Smell loss as an early sign (landmark 286) is one of the criteria's markers.

Outcome

Advanced as a research tool. Biology-based definitions built on the seed amplification assay (landmark 9; landmark 28) have since been proposed as an alternative for trial entry; whether they replace the clinical-prodromal route is not settled here. The criteria give probabilities, not a diagnosis, so accuracy for any one person is modest.

Sources

• Berg et al., Mov Disord 2015;30:1600–1611, DOI 10.1002/mds.26431, PMID 26474317
• Heinzel et al., Mov Disord 2019;34:1464–1470, DOI 10.1002/mds.27802, PMID 31412427
• No correction or retraction found for either paper (Crossref and Europe PMC, 20 Oct 2026). Abstracts of both were read via Europe PMC.
• Not yet verified: the exact list of markers in the 2015 version; how often the calculator has been validated in independent cohorts.