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Grant Details

Grant Number: 5R01CA172119-05 Interpret this number
Primary Investigator: Ahles, Tim
Organization: Sloan-Kettering Inst Can Research
Project Title: Cognition in Older Breast Cancer Survivors: Treatment Exposure, Apoe, & Smoking
Fiscal Year: 2017


DESCRIPTION (provided by applicant): Cognitive decline is one of the most feared consequences of aging among older adults and even minor changes in cognitive function can seriously impact function, ability to live independently, and quality of life. The trajectory of cognitive change with normal aging is influenced by factors including genetics, cognitive reserve, lifestyle, frailty, and comorbid medical conditions. Although there are compelling data suggesting a relationship between cancer, cancer therapy, and cognitive impairment the vast majority of these studies have focused on younger patients (<65 years old) and few studies have focused on 5+ year survivors. However, the majority of cancer survivors are older adults. Furthermore, those who were treated at an older age may be more vulnerable to cognitive decline because factors that influence normal cognitive aging may interact with cancer treatments to increase vulnerability. The objective of this application is to unite the fields of geriatrics, neuropsychology, oncology, and genetics to study the prevalence and trajectory of cognitive impairment in a cohort of older, long-term (5-15 years) survivors of breast cancer and matched healthy controls. Using a prospective, longitudinal study design, we will pursue the following specific aims while controlling for comorbidity and frailty: Aim 1: Examine the association of APOE status, smoking history, and therapeutic exposures on the cognitive performance among older breast cancer survivors compared to controls (age-, race- and education-matched) Aim 2: Utilize Growth Mixture Modeling techniques to determine trajectories of longitudinal change in cognitive function among older breast cancer survivors and controls (age-, race- and education-matched): Aim 3: Explore associations among cognitive reserve, APOE, smoking history and therapeutic exposures on cognitive functioning at study entry and the pattern of longitudinal change. This study is significant because it will fill a major gap in knowledge regarding the factors that increase risk for cognitive decline in older breast cancer survivors. These data are critical in order to weigh the risks and benefits of cancer treatment in the growing aging population. This study is innovative because it will examine the interactions of therapeutic exposures, genetic polymorphisms, and smoking history in predicting differences in cognitive performance between breast cancer survivors and controls controlling for burden of comorbidity and frailty. Furthermore, the longitudinal design will inform whether the trajectory of cognitive change for cancer survivors parallels healthy controls (phase shift hypothesis) or demonstrates a steeper slope (accelerated aging hypothesis). These data will serve as a foundation to identify older breast cancer survivors at risk for cognitive impairment and guide the development of rationale interventions to decrease this risk, with the ultimate goal of preserving the cognitive function and well-being of older survivors of cancer.


Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study.
Authors: Mandelblatt J.S. , Zhai W. , Ahn J. , Small B.J. , Ahles T.A. , Carroll J.E. , Denduluri N. , Dilawari A. , Extermann M. , Graham D. , et al. .
Source: Cancer, 2020-03-15; 126(6), p. 1183-1192.
EPub date: 2019-12-20.
PMID: 31860135
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Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype.
Authors: Carroll J.E. , Small B.J. , Tometich D.B. , Zhai W. , Zhou X. , Luta G. , Ahles T.A. , Saykin A.J. , Nudelman K.N.H. , Clapp J.D. , et al. .
Source: Cancer, 2019-12-15; 125(24), p. 4516-4524.
EPub date: 2019-09-25.
PMID: 31553501
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Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.
Authors: Guida J.L. , Ahles T.A. , Belsky D. , Campisi J. , Cohen H.J. , DeGregori J. , Fuldner R. , Ferrucci L. , Gallicchio L. , Gavrilov L. , et al. .
Source: Journal of the National Cancer Institute, 2019-12-01; 111(12), p. 1245-1254.
PMID: 31321426
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Intrinsic brain activity changes associated with adjuvant chemotherapy in older women with breast cancer: a pilot longitudinal study.
Authors: Chen B.T. , Jin T. , Patel S.K. , Ye N. , Ma H. , Wong C.W. , Rockne R.C. , Root J.C. , Saykin A.J. , Ahles T.A. , et al. .
Source: Breast cancer research and treatment, 2019 Jul; 176(1), p. 181-189.
EPub date: 2019-04-13.
PMID: 30989462
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Subcortical brain iron deposition and cognitive performance in older women with breast cancer receiving adjuvant chemotherapy: A pilot MRI study.
Authors: Chen B.T. , Ghassaban K. , Jin T. , Patel S.K. , Ye N. , Sun C.L. , Kim H. , Rockne R.C. , Mark Haacke E. , Root J.C. , et al. .
Source: Magnetic resonance imaging, 2018 12; 54, p. 218-224.
EPub date: 2018-08-02.
PMID: 30076946
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The Impact of Using Different Reference Populations on Measurement of Breast Cancer-Related Cognitive Impairment Rates.
Authors: Clapp J.D. , Luta G. , Small B.J. , Ahles T.A. , Root J.C. , Graham D. , Hurria A. , Jacobsen P.B. , Jim H. , McDonald B.C. , et al. .
Source: Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 2018-12-01; 33(8), p. 956-963.
PMID: 29471454
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Cognitive Effects of Cancer and Cancer Treatments.
Authors: Ahles T.A. , Root J.C. .
Source: Annual review of clinical psychology, 2018-05-07; 14, p. 425-451.
EPub date: 2018-01-18.
PMID: 29345974
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Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.
Authors: Chen B.T. , Sethi S.K. , Jin T. , Patel S.K. , Ye N. , Sun C.L. , Rockne R.C. , Haacke E.M. , Root J.C. , Saykin A.J. , et al. .
Source: Breast cancer research : BCR, 2018-05-02; 20(1), p. 38.
EPub date: 2018-05-02.
PMID: 29720224
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New Challenges in Psycho-Oncology Research IV: Cognition and cancer: Conceptual and methodological issues and future directions.
Authors: Ahles T.A. , Hurria A. .
Source: Psycho-oncology, 2018 01; 27(1), p. 3-9.
PMID: 29044730
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Integrating Frailty Research into the Medical Specialties-Report from a U13 Conference.
Authors: Walston J. , Robinson T.N. , Zieman S. , McFarland F. , Carpenter C.R. , Althoff K.N. , Andrew M.K. , Blaum C.S. , Brown P.J. , Buta B. , et al. .
Source: Journal of the American Geriatrics Society, 2017 Oct; 65(10), p. 2134-2139.
EPub date: 2017-04-19.
PMID: 28422280
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Aging, the Medical Subspecialties, and Career Development: Where We Were, Where We Are Going.
Authors: Hurria A. , High K.P. , Mody L. , McFarland Horne F. , Escobedo M. , Halter J. , Hazzard W. , Schmader K. , Klepin H. , Lee S. , et al. .
Source: Journal of the American Geriatrics Society, 2017 Apr; 65(4), p. 680-687.
EPub date: 2017-01-16.
PMID: 28092400
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Examining the Association between Patient-Reported Symptoms of Attention and Memory Dysfunction with Objective Cognitive Performance: A Latent Regression Rasch Model Approach.
Authors: Li Y. , Root J.C. , Atkinson T.M. , Ahles T.A. .
Source: Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 2016 Jun; 31(4), p. 365-77.
EPub date: 2016-04-24.
PMID: 27193366
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Learning and memory performance in breast cancer survivors 2 to 6 years post-treatment: the role of encoding versus forgetting.
Authors: Root J.C. , Andreotti C. , Tsu L. , Ellmore T.M. , Ahles T.A. .
Source: Journal of cancer survivorship : research and practice, 2016 06; 10(3), p. 593-9.
EPub date: 2015-12-12.
PMID: 26658913
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Reliable change in neuropsychological assessment of breast cancer survivors.
Authors: Andreotti C. , Root J.C. , Schagen S.B. , McDonald B.C. , Saykin A.J. , Atkinson T.M. , Li Y. , Ahles T.A. .
Source: Psycho-oncology, 2016 Jan; 25(1), p. 43-50.
EPub date: 2015-03-23.
PMID: 25808921
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Learning and memory performance in a cohort of clinically referred breast cancer survivors: the role of attention versus forgetting in patient-reported memory complaints.
Authors: Root J.C. , Ryan E. , Barnett G. , Andreotti C. , Bolutayo K. , Ahles T. .
Source: Psycho-oncology, 2015 May; 24(5), p. 548-55.
EPub date: 2014-07-05.
PMID: 25044928
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Cognitive effects of cancer systemic therapy: implications for the care of older patients and survivors.
Authors: Mandelblatt J.S. , Jacobsen P.B. , Ahles T. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014-08-20; 32(24), p. 2617-26.
EPub date: 2014-07-28.
PMID: 25071135
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Cognitive impairment in older patients with breast cancer before systemic therapy: is there an interaction between cancer and comorbidity?
Authors: Mandelblatt J.S. , Stern R.A. , Luta G. , McGuckin M. , Clapp J.D. , Hurria A. , Jacobsen P.B. , Faul L.A. , Isaacs C. , Denduluri N. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014-06-20; 32(18), p. 1909-18.
EPub date: 2014-05-19.
PMID: 24841981
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