Skip to main content
An official website of the United States government
Grant Details

Grant Number: 5R01CA231014-04 Interpret this number
Primary Investigator: Janelsins, Michelle
Organization: University Of Rochester
Project Title: Translational Neuroscience Approaches to Cancer-Related Cognitive Impairment: Measurement, Mechanisms, and Function
Fiscal Year: 2022


PROJECT SUMMARY Cancer-related cognitive impairment (CRCI) is a troublesome side effect reducing overall daily functioning for many breast cancer patients undergoing chemotherapy. In Dr. Janelsins’ NCI-funded nationwide, prospective cohort study, 45% of breast cancer patients report clinically significant post-chemotherapy (URCC10055; N=945); this is one of the largest studies of CRCI to date and the only one we are aware of in community oncology clinics. CRCI may also persist long-term; however, large studies incorporating pre-chemotherapy time-points are needed to clearly elucidate long-term trajectories of CRCI. In URCC10055, Dr. Janelsins and colleagues used two tests that address specific cognitive functions: 1) the Delayed Match to Sample (DMS) task—a visual working memory test with sensitivity to the prefrontal cortex dysfunction and with analogous features to the delayed spatial alternation test used in her CRCI mouse model, and 2) the Rapid Visual Processing Test (RVP)—a sustained attention test with sensitivity to parietal and frontal lobe dysfunction. With both the DMS and RVP tests, there was a significant decline in breast cancer patients receiving adjuvant chemotherapy from pre- to 6 months post-chemotherapy compared to age-matched controls assessed at the same times (N=943). By comparison, the standard neuropsychological tests did not reveal significant differences at this time-point suggesting they may lack sensitivity for assessing long-term decline. We also present preliminary data that the inflammatory pathways may be related to lower DMS scores. Based on our preclinical data, and literature of others, we will also add a new learning test to precisely address hippocampal function, the Paired Associated Learning (PAL) test. Our aims are to conduct a comprehensive assessment of long-term CRCI in specific cognitive functions of visual working memory (DMS; primary aim; Aim 1a), sustained attention (RVP; Aim 1b) and new learning (PAL; Aim 1c) at 7 and 9 years post-chemotherapy in breast cancer patients compared to controls, assessing specific factors leading to cognitive decline, and to assess the impact of long-term CRCI with these measures on daily function (Aim 2), inflammation (Aim 3), and relationship to other cognitive measures (standard neuropsychological, self-report; Aim 4). In order to address these innovative aims, we will leverage URCC10055 to collect new 7- and 9-year data on 450 breast cancer patients (survivors) and 300 controls. These time-points coincide with gaps in the literature in evaluating longitudinal, long-term CRCI and these are the time-points available during the funding period. In order to evaluate long-term longitudinal CRCI, we will also leverage the existing URCC10055 data (pre-chemotherapy, post-chemotherapy, and 6 months follow-up). This proposal will fill critical gaps in the field in our understanding of longitudinal long-term effects of CRCI from prior to chemotherapy, biologic processes involved, and impact on overall daily functioning. These cognitive measures could provide practical yet CRCI- specific screening methods in busy oncology clinics and inform future mechanistic and CRCI intervention trials.


Cognitive and neuroimaging outcomes in individuals with benign and low-grade brain tumours receiving radiotherapy: a protocol for a prospective cohort study.
Authors: Hardy S.J. , Finkelstein A.J. , Tivarus M. , Culakova E. , Mohile N. , Weber M. , Lin E. , Zhong J. , Usuki K. , Schifitto G. , et al. .
Source: BMJ open, 2023-02-15; 13(2), p. e066458.
EPub date: 2023-02-15.
PMID: 36792323
Related Citations

The association between cancer-related fatigue and diabetes from pre-chemotherapy to 6 months post-chemotherapy.
Authors: Kleckner A.S. , Kleckner I.R. , Culakova E. , Shayne M. , Belcher E.K. , Gudina A.T. , Williams A.M. , Onitilo A.A. , Hopkins J.O. , Gross H. , et al. .
Source: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2022 Sep; 30(9), p. 7655-7663.
EPub date: 2022-06-09.
PMID: 35678881
Related Citations

Exploratory Analysis of Associations Between Whole Blood Mitochondrial Gene Expression and Cancer-Related Fatigue Among Breast Cancer Survivors.
Authors: Kleckner A.S. , Kleckner I.R. , Culakova E. , Wojtovich A.P. , Klinedinst N.J. , Kerns S.L. , Hardy S.J. , Inglis J.E. , Padula G.D.A. , Mustian K.M. , et al. .
Source: Nursing research, 2022 Sep-Oct 01; 71(5), p. 411-417.
EPub date: 2022-04-13.
PMID: 35416182
Related Citations

Inflammation, Attention, and Processing Speed in Patients With Breast Cancer Before and After Chemotherapy.
Authors: Belcher E.K. , Culakova E. , Gilmore N.J. , Hardy S.J. , Kleckner A.S. , Kleckner I.R. , Lei L. , Heckler C. , Sohn M.B. , Thompson B.D. , et al. .
Source: Journal of the National Cancer Institute, 2022-05-09; 114(5), p. 712-721.
PMID: 35134984
Related Citations

Reply to S. Ning et al.
Authors: Salerno E.A. , Culakova E. , Heckler C.E. , Janelsins M.C. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2022-03-10; 40(8), p. 916-918.
EPub date: 2022-01-21.
PMID: 35061514
Related Citations

Relationships between cytokines and cognitive function from pre- to post-chemotherapy in patients with breast cancer.
Authors: Janelsins M.C. , Lei L. , Netherby-Winslow C. , Kleckner A.S. , Kerns S. , Gilmore N. , Belcher E. , Thompson B.D. , Werner Z.A. , Hopkins J.O. , et al. .
Source: Journal of neuroimmunology, 2022-01-15; 362, p. 577769.
EPub date: 2021-11-19.
PMID: 34871864
Related Citations

Longitudinal Changes in Cognitive Function in a Nationwide Cohort Study of Patients With Lymphoma Treated With Chemotherapy.
Authors: Janelsins M.C. , Mohamed M. , Peppone L.J. , Magnuson A. , Belcher E.K. , Melnik M. , Dakhil S. , Geer J. , Kamen C. , Minasian L. , et al. .
Source: Journal of the National Cancer Institute, 2022-01-11; 114(1), p. 47-59.
PMID: 34255086
Related Citations

Physical Activity Patterns and Relationships With Cognitive Function in Patients With Breast Cancer Before, During, and After Chemotherapy in a Prospective, Nationwide Study.
Authors: Salerno E.A. , Culakova E. , Kleckner A.S. , Heckler C.E. , Lin P.J. , Matthews C.E. , Conlin A. , Weiselberg L. , Mitchell J. , Mustian K.M. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021-10-10; 39(29), p. 3283-3292.
EPub date: 2021-08-18.
PMID: 34406822
Related Citations

Cognitive Function in Older Adults With Cancer: Assessment, Management, and Research Opportunities.
Authors: Magnuson A. , Ahles T. , Chen B.T. , Mandelblatt J. , Janelsins M.C. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021-07-01; 39(19), p. 2138-2149.
EPub date: 2021-05-27.
PMID: 34043437
Related Citations

Fatigue, anxiety, and quality of life in breast cancer patients compared to non-cancer controls: a nationwide longitudinal analysis.
Authors: Williams A.M. , Khan C.P. , Heckler C.E. , Barton D.L. , Ontko M. , Geer J. , Kleckner A.S. , Dakhil S. , Mitchell J. , Mustian K.M. , et al. .
Source: Breast cancer research and treatment, 2021 May; 187(1), p. 275-285.
EPub date: 2021-01-04.
PMID: 33392843
Related Citations

The longitudinal relationship between immune cell profiles and frailty in patients with breast cancer receiving chemotherapy.
Authors: Gilmore N. , Mohile S. , Lei L. , Culakova E. , Mohamed M. , Magnuson A. , Loh K.P. , Maggiore R. , Belcher E. , Conlin A. , et al. .
Source: Breast cancer research : BCR, 2021-02-05; 23(1), p. 19.
EPub date: 2021-02-05.
PMID: 33546731
Related Citations

Strategies to Prevent or Remediate Cancer and Treatment-Related Aging.
Authors: Guida J.L. , Agurs-Collins T. , Ahles T.A. , Campisi J. , Dale W. , Demark-Wahnefried W. , Dietrich J. , Fuldner R. , Gallicchio L. , Green P.A. , et al. .
Source: Journal of the National Cancer Institute, 2021-02-01; 113(2), p. 112-122.
PMID: 32348501
Related Citations

Associations of inflammation with frailty in patients with breast cancer aged 50 and over receiving chemotherapy.
Authors: Gilmore N. , Kadambi S. , Lei L. , Loh K.P. , Mohamed M. , Magnuson A. , Cole S. , Esparaz B.T. , Giguere J.K. , Mohile S. , et al. .
Source: Journal of geriatric oncology, 2020 Apr; 11(3), p. 423-430.
EPub date: 2019-04-13.
PMID: 30992181
Related Citations

Back to Top