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BMC Cancer
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

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

Authors: Herta H Chao, Edward Uchio, Sheng Zhang, Sien Hu, Sarah R Bednarski, Xi Luo, Michal Rose, John Concato, Chiang-shan R Li

Published in: BMC Cancer | Issue 1/2012

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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.
Appendix
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Literature
1.
Meng MV, Grossfeld GD, Sadetsky N, Mehta SS, Lubeck DP, Carroll PR: Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. Urology. 2002, 60 (Suppl 3A): 7-12.CrossRefPubMed
2.
Shahinian VB, Kuo Y-F, Freeman JL, Orihuela E, Goodwin JS: Increasing use of gonadotropin-releasing hormone agonists for localized prostate cancer. Cancer. 2005, 103: 1615-1624. 10.1002/cncr.20955.CrossRefPubMed
3.
Alibhai SM, Gogov S, Allibhai Z: Long-term side effects of androgen deprivation therapy in men with non-metastatic prostate cancer: a systematic literature review. Crit Rev Oncol Hematol. 2006, 60: 201-215. 10.1016/j.critrevonc.2006.06.006.CrossRefPubMed
4.
Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM: Free testosterone and risk for Alzheimer disease in older men. Neurology. 2004, 62: 188-193. 10.1212/WNL.62.2.188.CrossRefPubMed
5.
Kenny AM, Fabregas G, Song C, Biskup B, Bellantonio S: Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss. J Gerontol A Biol Sci Med Sci. 2004, 59: 75-78. 10.1093/gerona/59.1.M75.CrossRefPubMed
6.
Cherrier MM, Matsumoto AM, Amory JK, Johnson M, Craft S, Peskind ER, Raskind MA: Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men. Psychoneuroendocrinology. 2007, 32: 72-79. 10.1016/j.psyneuen.2006.10.008.CrossRefPubMed
7.
Cherrier MM, Matsumoto AM, Amory JK, Asthana S, Bremner W, Peskind ER, Raskind MA, Craft S: Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology. 2005, 64: 2063-2068. 10.1212/01.WNL.0000165995.98986.F1.CrossRefPubMed
8.
Lu PH, Masterman DA, Mulnard R, Cotman C, Miller B, Yaffe K, Reback E, Porter V, Swerdloff R, Cummings JL: Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol. 2006, 63: 177-185. 10.1001/archneur.63.2.nct50002.CrossRefPubMed
9.
Nelson CJ, Lee JS, Gamboa MC, Roth AJ: Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer. 2008, 113 (5): 1097-1106. 10.1002/cncr.23658.CrossRefPubMedPubMedCentral
10.
Joly F, Alibhai SM, Galica J, Park A, Yi QL, Wagner L, Tannock IF: Impact of androgen deprivation therapy on physical and cognitive function, as well as quality of life of patients with nonmetastatic prostate cancer. J Urol. 2006, 176: 2443-2447. 10.1016/j.juro.2006.07.151.CrossRefPubMed
11.
Almeida OP, Waterreus A, Spry N, Flicker L, Martins RN: One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men. Psychoneuroendocrinology. 2004, 29: 1071-1081. 10.1016/j.psyneuen.2003.11.002.CrossRefPubMed
12.
Green HJ, Pakenham KI, Headley BC, Yaxley J, Nicol DL, Mactaggart PN, Swanson C, Watson RB, Gardiner RA: Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: a randomized controlled trial. BJU Int. 2002, 90: 427-432. 10.1046/j.1464-410X.2002.02917.x.CrossRefPubMed
13.
Jenkins VA, Bloomfield DJ, Shilling VM, Edginton TL: Does neoadjuvant hormone therapy for early prostate cancer affect cognition? Results from a pilot study. BJU Int. 2005, 96: 48-53. 10.1111/j.1464-410X.2005.05565.x.CrossRefPubMed
14.
Salminen E, Portin R, Korpela J, et al: Androgen deprivation and cognition in prostate cancer. Br J Cancer. 2004, 89: 971-976.CrossRef
15.
Miller SP, McQuillen PS: Neurology of congenital heart disease: insight from brain imaging. Arch Dis Child Fetal Neonatal Ed. 2007, 92: F435-F437. 10.1136/adc.2006.108845.CrossRefPubMedPubMedCentral
16.
Korzeniewski SJ, Birbeck G, DeLano MC, Potchen MJ, Paneth N: A systematic review of neuroimaging for cerebral palsy. J Child Neurol. 2008, 23: 216-227.CrossRefPubMed
17.
Tan HY, Sust S, Buckholtz JW, Mattay VS, Meyer-Lindenberg A, Egan MF, Weinberger DR, Callicott JH: Dysfunctional prefrontal regional specialization and compensation in schizophrenia. Am J Psychiatry. 2006, 163: 1969-1977. 10.1176/appi.ajp.163.11.1969.CrossRefPubMed
18.
Driesen NR, Leung HC, Calhoun VD, Constable RT, Gueorguieva R, Hoffman R, Skudlarski P, Goldman-Rakic PS, Krystal JH: Impairment of Working Memory Maintenance and Response in Schizophrenia: Functional Magnetic Resonance Imaging Evidence. Biol Psychiatry. 2008, 64: 1026-1034. 10.1016/j.biopsych.2008.07.029.CrossRefPubMedPubMedCentral
19.
Koch K, Wagner G, Nenadic I, Schachtzabel C, Schultz C, Roebel M, Reichenbach JR, Sauer H, Schlosser RG: Fronto-striatal hypoactivation during correct information retrieval in patients with schizophrenia: an fMRI study. Neuroscience. 2008, 153: 54-62. 10.1016/j.neuroscience.2008.01.063.CrossRefPubMed
20.
Castellon SA, Silverman DH, Ganz PA: Breast cancer treatment and cognitive functioning: current status and future challenges in assessment. Breast Cancer Res Treat. 2005, 92: 199-206. 10.1007/s10549-005-5342-0.CrossRefPubMed
21.
Silverman DH, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L, Waddell K, Petersen L, Phelps ME, Ganz PA: Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy. Breast Cancer Res Treat. 2007, 103 (3): 303-311. 10.1007/s10549-006-9380-z.CrossRefPubMed
22.
Ferguson RJ, McDonald BC, Saykin AJ, Ahles TA: Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. J Clin Oncol. 2007, 25 (25): 3866-3870. 10.1200/JCO.2007.10.8639.CrossRefPubMedPubMedCentral
23.
Eberling JL, Wu C, Tong-Turnbeaugh R, Jagust WJ: Estrogen- and tamoxifen-associated effects on brain structure and function. NeuroImage. 2004, 21: 364-371. 10.1016/j.neuroimage.2003.08.037.CrossRefPubMed
24.
Deprez S, Amant F, Smeets A, Peeters R, Leemans A, Van Hecke W, Verhoeven JS, Christiaens MR, Vandenberghe J, Vandenbulcke M, Sunaert S: Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol. 2012, 30 (3): 274-281. 10.1200/JCO.2011.36.8571. Epub 2011 Dec 19CrossRefPubMed
25.
Kesler SR, Kent JS, O'Hara R: Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol. 2011, 68 (11): 1447-1453. 10.1001/archneurol.2011.245.CrossRefPubMedPubMedCentral
26.
Folstein MF, Folstein SE, McHugh PR: “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975, 12: 189-198. 10.1016/0022-3956(75)90026-6.CrossRefPubMed
27.
First MB, Spitzer RL, Williams JBW, Gibbon M: Structured Clinical Interview for DSM-IV (SCID). 1995, Washington DC: American Psychiatric Association
28.
Esper P, Mo F, Chodak G, Sinner M, Cella D, Pienta KJ: Measuring quality of life in men with prostate cancer using the functional assessment of cancer therapy-prostate instrument. Urology. 1997, 50: 920-928. 10.1016/S0090-4295(97)00459-7.CrossRefPubMed
29.
Baddeley A: Working memory: looking back and looking forward. Nature Reviews. Neuroscience. 2003, 4: 829-839.PubMed
30.
Kirchner WK: Age differences in short-term retention of rapidly changing information. J Exp Psychol. 1958, 55: 352-358.CrossRefPubMed
31.
Logan GD, Cowan WB, Davis KA: On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform. 1984, 10: 276-291.CrossRefPubMed
32.
Li C-SR, Chao HH-A, Lee TW: The neural correlates of speeded compared to delayed responses in a stop signal task: an indirect analogue of risk taking and association with an anxiety trait. Cerebral Cortex. 2009, 19: 839-848.CrossRefPubMed
33.
Chao HH, Luo X, Chang JL, Li CS: Activation of the pre-supplementary motor area but not inferior prefrontal cortex in association with short stop signal reaction time–an intra-subject analysis. BMC Neurosci. 2009, 10: 75-10.1186/1471-2202-10-75.CrossRefPubMedPubMedCentral
34.
Ridderinkhof KR, van den Wildenberg WP, Segalowitz SJ, Carter CS: Neurocognitive mechanisms of cognitive control: the role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning. Brain Cogn. 2004, 56: 129-140. 10.1016/j.bandc.2004.09.016.CrossRefPubMed
35.
Rushworth MF: Intention, choice, and the medial frontal cortex. Ann N Y Acad Sci. 2008, 1124: 181-207. 10.1196/annals.1440.014.CrossRefPubMed
36.
Li CS, Morgan PT, Matuskey D, Abdelghany O, Luo X, Chang JL, Rounsaville BJ, Ding YS, Malison RT: Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients. Proc Natl Acad Sci U S A. 2010, 107: 14455-14459. 10.1073/pnas.1002467107.CrossRefPubMedPubMedCentral
37.
Cohen J: Statistical Power Analysis for the Behavioral Sciences (second edition). 1988, Hillsdale, New Jersey: Lawrence Erlbaum Associates
38.
Brett M, Anton J-L, Valabregue R, Poline J-P: Region of interest analysis using an SPM toolbox. Abstract presented at the 8th International Conference on Functional Mapping of the Human Brain. June 2--6. 2002, Sendai, Japan, Available on CD-ROM in Neuro-Image, 16(2), abstract 497
39.
Fair DA, Schlaggar BL, Cohen AL, Miezin FM, Dosenbach NU, Wenger KK, Fox MD, Snyder AZ, Raichle ME, Petersen SE: A method for using blocked and event-related fMRI data to study "resting state" functional connectivity. NeuroImage. 2007, 35: 396-405. 10.1016/j.neuroimage.2006.11.051.CrossRefPubMedPubMedCentral
40.
Fox MD, Raichle ME: Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007, 8: 700-711. 10.1038/nrn2201.CrossRefPubMed
41.
Alibhai SM, Breunis H, Timilshina N, Marzouk S, Stewart D, Tannock I, Naglie G, Tomlinson G, Fleshner N, Krahn M, Warde P, Canning SD: Impact of androgen-deprivation therapy on cognitive function in men with nonmetastatic prostate cancer. J Clin Oncol. 2010, 28 (34): 5030-5037. 10.1200/JCO.2010.30.8742.CrossRefPubMed
42.
Azad N, Pitale S, Barnes WE, Friedman N: Testosterone treatment enhances regional brain perfusion in hypogonadal men. J Clin Endocrinol Metab. 2003, 88: 3064-3068. 10.1210/jc.2002-020632.CrossRefPubMed
43.
Forbes EE, Ryan ND, Phillips ML, Manuck SB, Worthman CM, Moyles DL, Tarr JA, Sciarrillo SR, Dahl RE: Healthy adolescents' neural response to reward: associations with puberty, positive affect, and depressive symptoms. J Am Acad Child Adolesc Psychiatry. 2010, 49: 162-72.e1-5.PubMedPubMedCentral
44.
Hermans EJ, Bos PA, Ossewaarde L, Ramsey NF, Fernández G, van Honk J: Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women. NeuroImage. 2010, 52: 277-283. 10.1016/j.neuroimage.2010.04.019.CrossRefPubMed
45.
Moffat SD, Resnick SM: Long-term measures of free testosterone predict regional cerebral blood flow patterns in elderly men. Neurobiol Aging. 2007, 28: 914-920. 10.1016/j.neurobiolaging.2006.04.001.CrossRefPubMed
46.
van Wingen GA, Zylicz SA, Pieters S, Mattern C, Verkes RJ, Buitelaar JK, Fernández G: Testosterone increases amygdala reactivity in middle-aged women to a young adulthood level. Neuropsychopharmacology. 2009, 34: 539-547. 10.1038/npp.2008.2.CrossRefPubMed
47.
Cherrier MM, Borghesani PR, Shelton AL, Higano CS: Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study. BMC Cancer. 2010, 10: 1-10.1186/1471-2407-10-1.CrossRefPubMedPubMedCentral
Metadata
Title
Effects of androgen deprivation on brain function in prostate cancer patients – a prospective observational cohort analysis
Authors
Herta H Chao
Edward Uchio
Sheng Zhang
Sien Hu
Sarah R Bednarski
Xi Luo
Michal Rose
John Concato
Chiang-shan R Li
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-371

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