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Androgen Deprivation Therapy Linked to Altered Brain Activity

A common treatment for prostate cancer has been linked to metabolic changes in brain regions associated with mood and higher-order cognitive functions

Jill Sakai, Contributor
Wednesday, June 6, 2018


U.S. Department of Energy via flickr


Androgen deprivation therapy (ADT), a common treatment for men with recurrent, nonmetastatic prostate cancer, has been associated with cognitive and mood changes such as spatial reasoning impairment, depression and anxiety. In addition, recent analyses have suggested that receiving ADT doubles a man’s risk of developing Alzheimer’s disease in the years following therapy.

A recent study in Prostate Cancer and Prostatic Diseases assessed brain activity in nine men receiving ADT for nonmetastatic prostate cancer. The men received nine months of leuprolide acetate and flutamide to achieve complete androgen blockade. Whole-brain imaging with positron emission tomography (PET) measured metabolic activity before and after ADT in eight of the nine patients. Cognitive and psychological tests were also performed to evaluate the men's spatial and verbal capabilities and mood.

All of the imaged subjects showed metabolic changes in brain areas associated with mood and higher-order cognitive processing, such as spatial reasoning and verbal memory. Many of these changes corresponded to changes in the subjects’ cognitive and psychological evaluations. For example, performance on a spatial reasoning task worsened after receiving ADT and was correlated with decreased activity in parts of the cingulate, parietal and temporal cortices. Lower metabolic activity in the hypothalamus after ADT was associated with higher levels of depression, irritability and anxiety.

The brain regions identified in the study overlap with areas associated with Alzheimer’s disease and Type 2 diabetes. Previous work has shown that testosterone and other androgens can influence the accumulation and processing of amyloid-b, a major contributor to the neuropathology of these disorders, suggesting that a common mechanism may underlie the cognitive and mood changes associated with ADT and other types of neurological decline.

The authors caution that interpretation of the study results is limited by the small number of subjects but suggest that the changes warrant further exploration in a larger population.