Androgen Deprivation Therapy and Cognitive Impairment
Abstract
Among the various therapeutic approaches, androgen deprivation therapy is a well-established treatment for prostate cancer. It involves reducing the level of male hormones or blocking their effects. Almost half of all prostate cancer patients receive androgen deprivation therapy over the course of their disease. Although this treatment strategy can slow disease progression, it has become apparent that an important side effect of androgen deprivation therapy is impairment of memory and learning. Patients receiving androgen deprivation therapy show significant declines in executive functioning, spatial reasoning, spatial abilities, and working memory. These problems are not trivial; they disrupt occupational and intellectual pursuits, affect social interactions, and reduce a patient s ability to make informed treatment decisions. Therefore, androgen deprivation-induced cognitive impairment has a direct and profound impact on quality of life by impairing the capability to function at the same level as before treatment. At the present time, little is known regarding the fundamental mechanisms underlying androgen deprivation therapy-induced impairment of cognition and this a critical gap in our knowledge base. In the hippocampus, a brain region that plays a major role in memory and learning, new nerve cells continue to develop throughout adulthood. This process is called neurogenesis and is involved in some aspects of memory and learning. Disruption of neurogenesis can produce cognitive deficits. Of fundamental importance to the goals and objectives of this project, androgens stimulate neurogenesis whereas a reduction in these hormones inhibits neurogenesis. Based upon these and other data, we hypothesize that impaired hippocampal neurogenesis underlies the androgen deprivation therapy-induced impairment of cognitive function. We will test this hypothesis by studying the effects of androgen deprivation on neurogenesis and memory and learning in the mouse. The results of the proposed experiments will provide proof-of-concept and set the groundwork for the future studies. The proposed experiments address a timely and important problem in prostate cancer survivorship and explore a highly innovative and new hypothesis. The first step in developing new treatments is to begin to understand the fundamental mechanism(s) underlying androgen deprivation therapy-induced impairment of cognitive function. The results of the proposed experiments could create an entirely new avenue for investigation and have a major impact on the development of strategies to prevent and/or treat this frequent and troubling problem in patients undergoing treatment for prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610429
Entities
People
- Robert Pechnick
Organizations
- United States Army
- Western University of Health Sciences