Grant Number:	5R01CA218501-05 Interpret this number
Primary Investigator:	Chao, Herta
Organization:	Yale University
Project Title:	Neurocognitive Changes From Long-Term Androgen Deprivation Therapy in Prostate Cancer Patients
Fiscal Year:	2022

ABSTRACT/SUMMARY The goal of this proposal is to examine the component and neural processes of cognitive impairment in prostate cancer patients undergoing androgen deprivation therapy (ADT). We will combine neurocognitive testing, clinical assessments, and brain imaging to examine cognitive impairment and its impact on quality of life and identify the structural and functional brain changes that predict the severity of cognitive deficits. Early detection of cognitive side effects of ADT would facilitate clinical decision making in the treatment and care of prostate cancer patients. ADT has proven efficacy in the treatment of many patients with metastatic prostate cancer. However, there is a lack of consensus in the indications for and optimal duration of ADT in prostate cancer patients without metastatic disease. Evidence grows to suggest that ADT may cause cognitive deficits that can have a negative impact on the quality of life in these patients. However, extant studies using traditional neuropsychological testing batteries have not consistently characterized ADT-induced cognitive impairment. It remains unclear whether or when these cognitive deficits will occur in a patient undergoing ADT, whether these deficits pertain broadly or only to specific cognitive domains, and whether the deficits are reversible. Furthermore, there are no established biomarkers that may predict cognitive deficits induced by ADT. Our preliminary findings suggest that cerebral changes may predate clinical manifestations of ADT-induced cognitive impairment. As many prostate cancer patients will receive ADT for many years or for life, according to current treatment protocols, it is of critical importance to identify individuals at risk for cognitive impairment. To this end, we propose to employ longitudinal neurocognitive and clinical assessments, as well as brain imaging, to identify cognitive impairment due to ADT and its impact on quality of life, to examine whether these changes depend on treatment duration and are reversible after a short duration of treatment, and to investigate cerebral markers that may predict cognitive impairment in a large cohort of prostate cancer patients undergoing ADT and control patients not receiving ADT. Our over-arching goal is to thoroughly evaluate the impact of ADT on cognition early during treatment. Studies of cognitive impairment in women receiving chemotherapy have influenced our thoughts about early treatment of breast cancer. Similarly, the findings from this study could enhance our understanding of the risks associated with ADT and inform clinical management of men with prostate cancer.




Ligand-gated ion channels as potential biomarkers for ADT-mediated cognitive decline in prostate cancer patients.
Authors: Verma S. , Singh V. , Nagampalli V. , Ponsky L.E. , Li C.R. , Chao H. , Gupta S. .
Source: Molecular Carcinogenesis, 2024-03-14 00:00:00.0; , .
EPub date: 2024-03-14 00:00:00.0.
PMID: 38482990
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Age-related reduction in anxiety and neural encoding of negative emotional memory.
Authors: Chaudhary S. , Zhang S. , Chen Y. , Dominguez J.C. , Chao H.H. , Li C.R. .
Source: Frontiers In Aging Neuroscience, 2024; 16, p. 1375435.
EPub date: 2024-07-03 00:00:00.0.
PMID: 39021704
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Androgen deprivation increases frontopolar cortical thickness in prostate cancer patients: an effect of early neurodegeneration?
Authors: Chaudhary S. , Roy A. , Summers C. , Ahles T. , Li C.R. , Chao H.H. .
Source: American Journal Of Cancer Research, 2024; 14(7), p. 3652-3664.
EPub date: 2024-07-15 00:00:00.0.
PMID: 39113873
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Sex differences in the effects of trait anxiety and age on resting-state functional connectivities of the amygdala.
Authors: Chaudhary S. , Hu S. , Hu K. , Dominguez J.C. , Chao H.H. , Li C.R. .
Source: Journal Of Affective Disorders Reports, 2023 Dec; 14, .
EPub date: 2023-08-28 00:00:00.0.
PMID: 38105798
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Age-related reduction in trait anxiety: Behavioral and neural evidence of automaticity in negative facial emotion processing.
Authors: Chaudhary S. , Zhang S. , Zhornitsky S. , Chen Y. , Chao H.H. , Li C.R. .
Source: Neuroimage, 2023-08-01 00:00:00.0; 276, p. 120207.
EPub date: 2023-05-30 00:00:00.0.
PMID: 37263454
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The effects of age on the severity of problem drinking: Mediating effects of positive alcohol expectancy and neural correlates.
Authors: Chaudhary S. , Chen Y. , Zhornitsky S. , Le T.M. , Zhang S. , Chao H.H. , Dominguez J.C. , Li C.R. .
Source: Addiction Biology, 2023 Jun; 28(6), p. e13278.
PMID: 37252876
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Does ADT Influence the Risk of Suicidal Ideation among US Veteran Prostate Cancer Patients Pre-Exposed to PTSD?
Authors: Brahmbhatt S. , Chao H.H. , Verma S. , Gupta S. .
Source: Cancers, 2023-05-12 00:00:00.0; 15(10), .
EPub date: 2023-05-12 00:00:00.0.
PMID: 37345076
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Brief Report: Implementation of a Universal Prescreening Protocol to Increase Recruitment to Lung Cancer Studies at a Veterans Affairs Cancer Center.
Authors: Xiang J.J. , Roy A. , Summers C. , Delvy M. , O'Donovan J. , Christensen J. , Dwy C. , Perry L. , Connery D. , Rose M.G. , et al. .
Source: Jto Clinical And Research Reports, 2022 Jul; 3(7), p. 100357.
EPub date: 2022-06-08 00:00:00.0.
PMID: 35815320
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Hypothalamic connectivities predict individual differences in ADT-elicited changes in working memory and quality of life in prostate cancer patients.
Authors: Chaudhary S. , Roy A. , Summers C. , Zhornitsky S. , Ahles T. , Li C.R. , Chao H.H. .
Source: Scientific Reports, 2022-06-10 00:00:00.0; 12(1), p. 9567.
EPub date: 2022-06-10 00:00:00.0.
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The effects of androgen deprivation on working memory and quality of life in prostate cancer patients: The roles of hypothalamic connectivity.
Authors: Chaudhary S. , Zhornitsky S. , Roy A. , Summers C. , Ahles T. , Li C.R. , Chao H.H. .
Source: Cancer Medicine, 2022-03-22 00:00:00.0; , .
EPub date: 2022-03-22 00:00:00.0.
PMID: 35315585
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Cerebral Volumetric Correlates of Apathy in Alzheimer's Disease and Cognitively Normal Older Adults: Meta-Analysis, Label-Based Review, and Study of an Independent Cohort.
Authors: Chaudhary S. , Zhornitsky S. , Chao H.H. , van Dyck C.H. , Li C.R. .
Source: Journal Of Alzheimer's Disease : Jad, 2022; 85(3), p. 1251-1265.
PMID: 34924392
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Emotion Processing Dysfunction in Alzheimer's Disease: An Overview of Behavioral Findings, Systems Neural Correlates, and Underlying Neural Biology.
Authors: Chaudhary S. , Zhornitsky S. , Chao H.H. , van Dyck C.H. , Li C.R. .
Source: American Journal Of Alzheimer's Disease And Other Dementias, 2022 Jan-Dec; 37, p. 15333175221082834.
PMID: 35357236
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Hypothalamic Functional Connectivity and Apathy in People with Alzheimer's Disease and Cognitively Normal Healthy Controls.
Authors: Chaudhary S. , Zhornitsky S. , Chao H.H. , van Dyck C.H. , Li C.R. .
Source: Journal Of Alzheimer's Disease : Jad, 2022; 90(4), p. 1615-1628.
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Effects of androgen deprivation on white matter integrity and processing speed in prostate cancer patients.
Authors: Chaudhary S. , Roy A. , Summers C. , Ahles T. , Li C.R. , Chao H.H. .
Source: American Journal Of Cancer Research, 2022; 12(10), p. 4802-4814.
EPub date: 2022-10-15 00:00:00.0.
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Cognitive dysfunction and cerebral volumetric deficits in individuals with Alzheimer's disease, alcohol use disorder, and dual diagnosis.
Authors: Zhornitsky S. , Chaudhary S. , Le T.M. , Chen Y. , Zhang S. , Potvin S. , Chao H.H. , van Dyck C.H. , Li C.R. .
Source: Psychiatry Research. Neuroimaging, 2021-11-30 00:00:00.0; 317, p. 111380.
EPub date: 2021-08-29 00:00:00.0.
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The effects of age on reward magnitude processing in the monetary incentive delay task.
Authors: Dhingra I. , Zhang S. , Zhornitsky S. , Le T.M. , Wang W. , Chao H.H. , Levy I. , Li C.R. .
Source: Neuroimage, 2020-02-15 00:00:00.0; 207, p. 116368.
EPub date: 2019-11-16 00:00:00.0.
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Androgen Deprivation Therapy and Cognitive Function in Prostate Cancer.
Authors: Kluger J. , Roy A. , Chao H.H. .
Source: Current Oncology Reports, 2020-02-11 00:00:00.0; 22(3), p. 24.
EPub date: 2020-02-11 00:00:00.0.
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The effects of age on cerebral responses to self-initiated actions during social interactions: An exploratory study.
Authors: Wang W. , Zhornitsky S. , Chao H.H. , Levy I. , Joormann J. , Li C.R. .
Source: Behavioural Brain Research, 2020-01-27 00:00:00.0; 378, p. 112301.
EPub date: 2019-10-20 00:00:00.0.
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Age-Related Changes in the Neural Processes of Reward-Directed Action and Inhibition of Action.
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Source: Frontiers In Psychology, 2020; 11, p. 1121.
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Imaging the effects of age on proactive control in healthy adults.
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