First, to study the effect of the presence of the LRRK2 G2019S mutation on brain activation patterns in PD patients who recently converted into a diseased state by comparing carriers to non carriers using fMRI and DTI technology. Second, to examine
the relationships between the presence of the mutation and brain activation patterns among healthy first degree relatives of PD patients who carry the G2019S mutation in order to identify and characterize between group differences which may serve as potential biological markers for sub-clinical diseased state.
A total of 100 healthy first degree relatives of LRRK2 G2019S positive PD patients as well as 10 PD patients will be enrolled in this study. Half of the subjects will carry the LRRK2 mutations and half will be non carriers. Subjects will undergo a 2.5 hour MRI scan that will include both structural scans (DTI and SPGR) as well as functional scans during cognitive and motor scans (Stroop, N-Back, Rest, Domino, Motor Imagery and short movie clips). Each task is related to recognized impaired functions in PD patients (motor, cognition, affect and reward processing). Differences between groups will be analyzed and correlated to behavioral data collected.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
The G2019S LRRK2 mutation is the most common genetic cause for PD. Healthy first degree relatives are a unique "at risk" population for the future development of PD. Utilizing fMRI technology should enable us to identify pre-motor neural differences in the carrier population which could be considered as compensatory mechanisms. Elucidating these mechanisms will assist in the understanding of PD progression and enable the development of new therapies that target the pre-motor phase of the disease.
We propose that the combination of clinical, imaging and genetic testing obtained in this study will demonstrate significant differences between PD patient carriers of the LRRK2 mutation, healthy mutation carriers and controls, enabling the identification of individuals with a high risk for developing PD as well as shedding light on the temporal dynamics of pre-motor PD.