title: Effects of androgen deprivation on brain function in prostate cancer patients - a prospective observational cohort analysis.
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.
authors.affiliation: Department of Internal Medicine & Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06519, USA. herta.chao@yale.edu
authors.forename: Herta H
authors.initials: HH
authors.lastname: Chao
authors.forename: Edward
authors.initials: E
authors.lastname: Uchio
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Sien
authors.initials: S
authors.lastname: Hu
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Bednarski
authors.forename: Xi
authors.initials: X
authors.lastname: Luo
authors.forename: Michal
authors.initials: M
authors.lastname: Rose
authors.forename: John
authors.initials: J
authors.lastname: Concato
authors.forename: Chiang-shan R
authors.initials: CS
authors.lastname: Li
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D015331:Cohort Studies; D017273:Goserelin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011597:Psychomotor Performance / Q000187:drug effects; D011788:Quality of Life; D011795:Surveys and Questionnaires; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; C053541:bicalutamide