The Neural Basis of Apathy in Frontotemporal Degeneration: A Longitudinal Study

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Project Summary The purpose of this individual National Research Service Award (NRSA) is to provide postdoctoral research training for a neuroscience nurse to become an independent investigator focusing on the behavioral and biological mechanisms that contribute to neuropsychiatric syndromes such as apathy in patients with neurodegenerative disease (ND). In addition to coursework and the acquisition of new research skills, I propose to focus this NRSA on impairments of goal-directed behavior (GDB) that are very common but understudied in ND. The syndrome of apathy, defined as a reduction in self-generated or voluntary behavior,1 has profound consequences for morbidity and mortality in the patient and for family caregiver burden. Treatments for apathy are hindered because of our poor understanding of the mechanisms underlying this behavior. In my cross-sectional dissertation data (funded by NINR F31NR013306), I identified three subtypes of apathy in patients with behavioral variant Frontotemporal Degeneration (bvFTD): difficulty with initiation, planning or motivation. Each subtype is related to disease in distinct frontal regions. Based on preliminary longitudinal data, I will collect additional data to test the hypothesis that subtypes of apathy will worsen over time, and that decline will be restricted to the subtype of initial impairment. I will also extend my research program to investigate how biologic and environmental factors contribute to worsening in apathy. I have had more than 8 years of experience as an Advanced Practice Nurse and Research Nurse Coordinator in a nationally ranked laboratory that studies the neural basis for behavior in ND. I have direct access to research participants as well as a large database of genetic and neuroimaging data that I will incorporate into my analyses. My research training will be guided by two internationally known scientists, Dr. Ann Kolanowski, a well-known gerontological nurse expert and leader, and Dr. Murray Grossman, a highly acclaimed cognitive neurologist and experienced scientist. The interdisciplinary training during the performance of this work will serve as an essential component in attaining my career goal to become an independent neuroscience nurse researcher. The long-term impact of this research training will be profound for patients with ND, their caregivers, and families. Knowledge of the natural history of apathy is essential in the development of interventions for subtypes of apathy. Consistent with the National Institute of Nursing Research (NINR) priorities, this innovative work will lead to a better understanding of these brain behavior relationships and with this new knowledge, tailored interventions will be designed to reduce apathy and the poor health outcomes that are associated with this devastating condition.