ADT and brain dysfunction in prostate ca: the effects of age & neural plasticity

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The goal of this proposal is to combine neurocognitive testing, clinical assessments, and neuroimaging to examine cognitive dysfunction in patients with early stage prostate cancer undergoing androgen deprivation therapy (ADT). Specifically, the effects of age and baseline testosterone level on ADT-elicited cognitive deficits and the neural bases underlying these deficits will be studied. ADT has proven efficacy in the treatment of many patients with prostate cancer. However, there is a lack of consensus in the need or indications for ADT in early stage prostate cancer. Evidence grows to suggest that ADT causes cognitive deficits which may have a negative impact on the quality of life. On the other hand, little is known about whether or when these cognitive deficits will occur in patients undergoing ADT or whether these deficits depend on age and pre-treatment testosterone level. Systematic longitudinal studies investigating the neural bases of cognitive deficits induced by ADT are lacking. In an earlier pilot study using brain imaging we showed that 6 months of ADT was associated with both structural and functional brain changes in elderly prostate cancer patients without demonstrating an explicit decline in neuropsychological test performance. These findings suggest brain imaging as a useful tool to identify early changes in cerebral structure and function in association with ADT and that elderly patients may compensate for task performance with neural plasticity. On the other hand, it is likely that more precise neurocognitive testing is needed to detect changes in cognition. Further, it remains unclear whether younger patients with prostate cancer will exhibit similar structural and functional brain changes and whether a greater proportional drop in testosterone as result of ADT compared to pre-treatment baseline could have a more detrimental impact on cognitive function and quality of life, as compared to older patients. This application proposes to employ neurocognitive tests focusing on executive control, attention, and working memory, clinical interviews, and multiple brain imaging modalities to identify cognitive dysfunction and pattern of cerebral changes due to ADT in 96 patients with early stage prostate cancer. Ninety-six age matched patients who do not undergo ADT will be studied as a control group. The findings will be correlated with quality of life assessments and subjective cognitive symptoms reported by the same individuals and the age and pre-treatment testosterone level of the patient. The results from this study will enhance our understanding of the effects of ADT on cognitive function and are highly relevant to younger patients undergoing adjuvant hormonal treatment for non-metastatic prostate cancer, as the majority of these patients are expected to be cured from prostate cancer and continue to be productive in society. Probably just as important is the potential impact of ADT on the expanding elderly populations, in which ADT may potentiate cognitive dysfunction and compromise quality of life.