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Open Access Research article

Effects of androgen deprivation on brain function in prostate cancer patients – a prospective observational cohort analysis

Herta H Chao129*, Edward Uchio3, Sheng Zhang4, Sien Hu4, Sarah R Bednarski4, Xi Luo5, Michal Rose12, John Concato126 and Chiang-shan R Li478

Author affiliations

1 Department of Internal Medicine & Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06519, USA

2 Medical Service, VA Connecticut Health Care System, West Haven, CT 06516, USA

3 Tower Research, Los Angeles, CA, 90048, USA

4 Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06519, USA

5 Department of Biostatistics, Brown University School of Medicine, Providence, RI, 02912, USA

6 Clinical Epidemiology Research Center, West Haven, CT, 06516, USA

7 Department of Neurobiology, Yale University School of Medicine, New Haven, CT, 06520, USA

8 Interdepartment Neuroscience Program, Yale University, New Haven, CT, 06520, USA

9 Cancer Center, VA Connecticut Health Care System, 950 Campbell Avenue, West Haven, CT, 06516, USA

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Citation and License

BMC Cancer 2012, 12:371  doi:10.1186/1471-2407-12-371

Published: 27 August 2012

Abstract

Background

Despite a lack of consensus regarding effectiveness, androgen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer. To examine a particular clinical concern regarding the possible impact of ADT on cognition, the current study combined neuropsychological testing with functional magnetic resonance imaging (fMRI) to assess both brain activation during cognitive performance as well as the integrity of brain connectivity.

Methods

In a prospective observational cohort analysis of men with non-metastatic prostate cancer at a Veterans Affairs medical center, patients receiving ADT were compared with patients not receiving ADT at baseline and at 6 months. Assessments included fMRI, the N-back task (for working memory), the stop-signal task (for cognitive control), and a quality of life questionnaire.

Results

Among 36 patients enrolled (18 in each group), 30 completed study evaluations (15 in each group); 5 withdrew participation and 1 died. Results for the N-back task, stop-signal task, and quality of life were similar at 6 months vs. baseline in each group. In contrast, statistically significant associations were found between ADT use (vs. non use) and decreased medial prefrontal cortical activation during cognitive control, as well as decreased connectivity between the medial prefrontal cortex and other regions involved with cognitive control.

Conclusions

Although ADT for 6 months did not affect selected tests of cognitive function, brain activations during cognitive control and functional brain connectivity were impaired on fMRI. The long-term clinical implications of these changes are not known and warrant future study.

Keywords:
Androgen deprivation; Prostate cancer; Brain function; Cognitive function