The overall goal of this K23 proposal is to provide the necessary training for the candidate to pursue a career as an independent clinical investigator. The didactic portion of the training will include participation in a K30 training grant in clinical research. As part of the curriculum, the candidate will enroll in the UM's School of Public Health and obtain a Master's of Science degree in clinical research design and statistical analysis. In addition, the candidate will have regular meetings with her mentor and participate in other regular educational activities related to her career plan. The investigator will also have extensive formal and informal interactions with the active community of neuroimaging researchers at the UM. The goal of the research portion of the training proposal is to evaluate the role nigrostriatal dopaminergic innervation changes play in the decline of motor performance associated with normal aging and Parkinson's disease (PD). Nigrostriatal dopaminergic innervation will be measured with [11C]-(+)-dihydrotetrabenazine positron emission tomography (DTBZ-PET). Cerebral blood flow activation of relevant motor regions will also be determined during a motor task using PET with [150]H20. Several standardized behavioral measures of motor performance will also be evaluated. In normal subjects, the density of striatal presynaptic dopaminergic terminals will be measured and motor performance and cerebral activation will be evaluated to determine whether there is a correlated decline in these measures with aging. Subjects with mild PD will be assessed in a similar manner to determine whether the reduction in presynaptic dopaminergic innervation correlates with the severity of motor deficits and cerebral blood flow. Finally, the dopamine agonist, apomorphine, will be administered to determine whether the deficits in motor performance and in cerebral activation can be reversed. The didactic and research portions of of this proposal will enable the candidate to achieve her goals of becoming an independent clinical investigator.
