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Grant Details

Grant Number: 5R01CA218501-04 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: 2021


Abstract

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.



Publications

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; 12(1), p. 9567.
EPub date: 2022-06-10.
PMID: 35688928
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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; , .
EPub date: 2022-03-22.
PMID: 35315585
Related Citations

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
Related Citations

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
Related Citations

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; 317, p. 111380.
EPub date: 2021-08-29.
PMID: 34482052
Related Citations

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; 207, p. 116368.
EPub date: 2019-11-16.
PMID: 31743790
Related Citations

Androgen Deprivation Therapy and Cognitive Function in Prostate Cancer.
Authors: Kluger J. , Roy A. , Chao H.H. .
Source: Current oncology reports, 2020-02-11; 22(3), p. 24.
EPub date: 2020-02-11.
PMID: 32048059
Related Citations

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; 378, p. 112301.
EPub date: 2019-10-20.
PMID: 31644928
Related Citations

Imaging the effects of age on proactive control in healthy adults.
Authors: Hu S. , Job M. , Jenks S.K. , Chao H.H. , Li C.R. .
Source: Brain imaging and behavior, 2019 Dec; 13(6), p. 1526-1537.
PMID: 31011949
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