Prodromal Parkinson's disease

The diagnosis of Parkinson's disease (PD) continues to be established only by the presence of cardinal motor features: hypokinesia, tremor and rigidity, according to UK Brain Bank Criteria or Movement Disorder Society (MDS) Definition Criteria. “Prodromal Parkinson” defines the complexity of early non-motor signs and risk factors for PD, as MDS Research Criteria for Prodromal PD latest updated in 2021 as an evidence-based conceptual framework. It includes a variable combination of symptoms such as REM-sleep behavior disorder (highest likelihood ratio), sleep-wake regulation dysfunction, hyposmia, constipation, and symptoms of the autonomic nervous system such as orthostatic hypotension, and early psychiatric symptoms such as depression or anxiety. Recently, new markers were added and comprise diabetes, global cognitive deficit, physical inactivity, and low plasma urate levels in men, ultrasound findings in the substantia nigra and genetic markers. From the early Honolulu-Asia Aging Study and several other US and European cohort studies (Predict-PD) impaired executive function, subtle motor dysfunction and tremor were highly indicative for the development of PD. Many of these features are unspecific and difficult to disentangle in clinical practice such as subtle slowness of movements in the elderly from an early bradykinesia. Unfortunately, none of these parameters is present in each single PD patient, some PD patients even miss many of these non-motor features or develop them later in the disease. Therefore the term “Prodromal Parkinson” still depends on likelihood ratios and will develop with further evidence in larger prospective cohorts to delineate the most specific pattern of premotor signs.