Prospective validation of risk markers for the development of Parkinsonís disease
Promising Outcomes of Original Grant:
As Parkinsonís disease is diagnosed when already a number of neurons have degenerated the PRIPS cohort consisting of 1847 healthy subjects older than 50 years was established to assess PD risk markers before motor dysfunction becomes evident. At the first investigation (baseline) among others the putative premotor markers substantia nigra hyperechogenictiy (SN+), assessed by transcranial ultrasound and hyposmia were assessed. At the first follow up, three years later, 11 subjects had developed PD. 80% of these had the ultrasound feature SN+ at baseline. With regard to the whole cohort we could calculate that SN+ increases the risk for PD in this age group for more than 17% in the given time frame. Hyposmia at baseline did not additionally increase the risk for PD.
Objectives for Supplemental Investigation:†
Besides SN+ and hyposmia a number of other markers and symptoms are discussed to antedate PD Ė i.e. sleep problems (specifically rem sleep behaviour disorder, RBD), autonomic dysfunction (like constipation and others), depression etc. All of these symptoms are frequent in the elderly population and will not necessarily lead to PD later in life. However, it could be that the combination of several of these markers and symptoms in motorically still healthy subjects could help to define those, in whom the neurodegenerative process has already started but has not lead to the typical motor symptoms. A large number of the currently discussed premotor markers have been assessed at the first follow up. The second follow up is planned to verify the results of the first follow up and to additionally calculate the influence of other markers/symptoms for the development of PD.
Importance of This Research for the Development of a New PD Therapy:
So far therapy in PD is primarily Symptoms & Side Effects. The fact the disease modulating or neuroprotective therapies have not been successful so far is related to the late diagnose Ė a large number of neurons have already degenerated when motor symptoms allow the diagnosis of PD. With this second follow up we hope to be able to provide a premotor battery Ė i.e. a combination of markers and symptoms that may help to identify those who are very likely to develop PD later in life. So far, there exist no side-effect therapeutic therapies for subjects who may be at risk for PD. However, in numerous research activities all over the world neuroprotective strategies are sought. With a population diagnosed earlier, it is hoped to delay or even prevent the still inevitably progressive course of PD.
Professor, Department for Neurodegenerative Diseases at Centre of Neurology and Hertie-Institute for Clinical Brain Research, University Hospital Tuebingen
Location: Tuebingen, Germany
Director at Department of Neurology, Medical University of Innsbruck, Austria
Location: Innsbruck, Austria
Doctor at Department of Neurology, University Hospital, Saarland University
Location: Homburg Saar, Germany