Effects of ADT on motivation and emotion function in prostate cancer patients: longitudinal imaging and prediction

PROJECT SUMMARY/ABSTRACT Androgen deprivation therapy (ADT) has proven efficacy in the treatment of metastatic prostate cancer. However, ADT is associated with physiological and cognitive side effects, and the risks and benefits of ADT for men without metastases remain unclear. Identification and evaluation of these side effects of ADT is critical to the management and care of these patients, many of whom are expected to be cured from cancer. The literature is mixed in terms of the domain, extent, and severity of cognitive impairment. Individuals vary in the impact of ADT likely because some patients but not others are able to functionally compensate for the effects of ADT, much like the effects of aging on cognitive functions. Investigators have characterized the overall deleterious effects of ADT on physical and mental health in terms of accelerated aging. Aging is associated with altered motivation and emotion. Individuals with Alzheimer’s disease and related dementia (ADRD) may exhibit apathy, which, along with anxiety and depression, manifests early, influences cognition, and severely restricts quality-of-life in the course of illness. The etiological processes of ADRD are multifactorial and research has provided evidence in support of the roles of diminishing levels of androgen. Thus, with the side effects conceptualized as accelerated aging, ADT may lead to motivation deficit as well as anxiety and depression in prostate cancer patients. We propose to combine clinical evaluation, neurocognitive testing, and brain imaging in a longitudinal setting to systematically investigate emotional processing and motivation dysfunction in prostate cancer patients undergoing ADT. We hypothesize that prostate cancer patients who undergo ADT relative to those who do not will demonstrate apathy and greater anxiety and depression in clinical and laboratory assessments. Further, ADT will alter hypothalamic and medial prefrontal cortical circuit activity each in relation to apathy and emotion dysfunction. With the longitudinal design, we will investigate how hypothalamus and medial prefrontal cortical circuit function at baseline predict these clinical manifestations and quality-of-life during follow-ups. Further, we will explore whether apathy, anxiety and depression may account for individual variation in cognitive dysfunction as a result of ADT. Our over-arching goal is to investigate motivation and emotion dysfunction and their neural markers in prostate cancer patients undergoing ADT. The findings will advance our understanding of the risks associated with ADT and facilitate clinical decision-making and rehabilitative interventions to preserve cognitive and affective functions and quality-of-life in the care of prostate cancer patients.