Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer

• Published in: Prostate cancer and prostatic diseases 2018-09, Vol.21 (3), p.394-402
• Main Authors: Cherrier, M. M., Cross, D. J., Higano, C. S., Minoshima, S.
• Format: Article
• Language: English
• Subjects: 59/78; 692/308/575; 692/699/67/1059; Acetic acid; Affect - drug effects; Aged; Alzheimer's disease; Androgen Antagonists - adverse effects; Androgens; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomedical and Life Sciences; Biomedicine; Brain; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Brain mapping; Brain stem; Cancer; Cancer Research; Cerebellum; Cognition; Cognition & reasoning; Cognition - drug effects; Correlation; Deprivation; Diabetes mellitus; Emission analysis; Flutamide; Flutamide - adverse effects; Glucose metabolism; Health risks; Humans; Hypothalamus; Kallikreins - blood; Leuprolide - adverse effects; Male; Men; Metabolism; Metastases; Middle Aged; Mood; Positron emission; Positron emission tomography; Prostate cancer; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Quality of Life; Spatial memory; Temporal gyrus; Thalamus; Therapy; Tomography
• ISSN: 1365-7852; 1476-5608; 1476-5608
• DOI: 10.1038/s41391-018-0037-x

Objective Androgen deprivation therapy (ADT) is a common treatment option for men with biochemical relapse from prostate cancer. ADT is associated with changes in mood, cognition, and quality of life, and most recently with increased risk for Alzheimer’s disease (AD). This study examined changes in brain metabolism using positron emission tomography (PET) in men undergoing intermittent ADT. Methods Nine men with prostate cancer and a rising PSA (biochemical recurrence) without evidence of metastases were treated with intermittent ADT consisting of 9 months of complete androgen blockade achieved with combined leuprolide acetate and flutamide. Patients underwent resting [Fuorine-18] fluorodeoxyglucose PET ( 18 F-FDGPET) at baseline (before treatment) and again after 9 months of ADT. Results Whole-brain mapping analysis after 9 months of androgen deprivation compared to pretreatment baseline revealed decreased regional cerebral glucose metabolism in the cerebellum, posterior cingulate, and medial thalamus bilaterally. Associations of brain metabolism with measurements of cognition and mood while on androgen deprivation revealed positive correlations between the posterior cingulate, left inferior parietal lobule (BA40), and left mid temporal gyrus (BA39) and spatial reasoning and a negative correlation between left inferior parietal lobule and verbal memory. Several mood indices were negatively correlated with hypothalamus and brainstem. Conclusion These findings suggest that complete androgen deprivation may result in changes in regional brain metabolism associated with variation in mood, verbal memory, and spatial performance. Brain regions that were impacted from ADT are similar and overlap with brain regions with metabolic decline found in early AD and diabetes, suggesting possible common mechanisms.