Markers and Time Course of Neurodegenerative Risk with Androgen Deprivation Therapy

Androgen deprivation is associated with an increased risk for neurodegeneration in both animal models and humans. Therefore the overall objective of this research program is to understand whether androgen deprivation therapy ADT decreases the quality of survival by amplifying age-related cognitive decline and increasing the risk for neurodegenerative disease. We focus in this report on findings of brain white matter degeneration using diffusion tensor imaging. We found that men on ADT or had ever used ADT had reduced prefrontal white matter integrity as compared to healthy elderly. In addition, white matter integrity in men on ADT was not related to age whereas it declined with increasing age in healthy men as well as in men with prostate cancer who are not on ADT. The findings were specific prefrontal white matter was affected by ADT treatment but not anterior or posterior callosum. The diffusivity data suggests the changes are due to axon drop out not loss of myelin as there were no treatment effects on transverse diffusivity. We hypothesize that ADT may accelerate cortical brain aging, followed by relative stability in white matter integrity thereafter.