Parkinson disease (PD) has a pre-clinical phase characterized by death of dopamine neurons in the substantia nigra and other brain regions, which precedes the development of Symptoms & Side Effects disease by years. Changes in neuroimaging, sleep, smell as well as autonomic and movement function tests are present in this pre-clinical period. Developing robust methods for detection of pre-clinical PD will help characterize the natural history of pre-clinical disease, and allow the development of markers to assess at risk individuals.
In order to evaluate the preclinical onset of PD and to identify optimal strategies for identifying individuals at very high risk for PD, we will develop a battery of tests that best distinguishes LRRK2 mutation carriers who have not developed Parkinson’s from two groups of control subjects: first-degree relatives of PD patients who do not have LRRK2 mutations and unrelated controls. We will first assess how well Individual tests of the Test Battery, which include spiral indices, smell tests, measures of autonomic nervous system function, mood measures, sleep ratings and brain ultrasound will distinguish non-manifesting carriers from both groups of control subjects. We will then combine the tests and determine which subset of tests are most predictive, and develop a battery summary score that best separates the groups.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Because some innovative treatments for Parkinson’s may be started too late in the disease process, it is important to identify individuals who are at high risk for developing Parkinson’s. Determining a non-invasive biomarker battery to identify at-risk individuals, could improve early detection of PD, and set the stage for earlier treatment and the testing of treatments that modify the natural history or prevent the onset of disease. It will also facilitate trial design for testing of LRRK2 related targets.
The goals are to use a parsimonious set of measures to characterize the pre-clinical development of PD and to identify specific features that are present in individuals who carry the LRRK2 G2019S mutation, but do not have Parkinson’s. This will also allow us to develop a pre-clinical battery that may be generalizable to a larger population to detect other high-risk groups.