Grant Number:	1R01CA122934-01A1 Interpret this number
Primary Investigator:	Schultz, Susan
Organization:	University Of Iowa
Project Title:	Elderly Cancer Survivors: Cognitive Outcomes and Markers of Neurodegeneration
Fiscal Year:	2007

DESCRIPTION (provided by applicant): Breast cancer is a great public health concern, but fortunately it is very treatable with high survival rates such that the majority of women are able to remain disease-free for many decades. As a result, a large cohort of women are now reaching late-life who have received previous treatments including chemotherapy, and they are now at an age where the development of memory decline becomes a concern. Hence it is of great interest to learn whether treatment for breast cancer increases the likelihood of cognitive decline in the elder years. This project will build on the "Integrating Aging and Cancer Research" program at the University of Iowa which encourages multidisciplinary collaborations that may lead to new insights into late-life outcomes. This revised application will determine the longitudinal effects of previous chemotherapy on late-life cognitive changes. The Iowa Cancer Registry of the State Health Registry will provide valuable assistance in identifying women who have survived more than 10 years and are now over age 65 and residing in southeast Iowa. In response to the previous reviews this study will now enroll a well-defined sample that will exclude participants who have also received radiation to create a homogenous group. The comprehensive neuropsychological assessment will be combined with state of the art magnetic resonance and diffusion tensor imaging to permit an analysis of regional brain differences in relation to cognitive outcomes. Previous studies have detected cognitive changes following acute treatment, but no studies have focused on the elderly population of long-term survivors. This application responds to Program Announcement (PA) Number: PA-05-142 "Biobehavioral Methods to Improve Outcomes Research" with an objective to foster "development of collaborative studies to expand the understanding of biobehavioral factors that influence disease prevention, improve health outcomes, or increase quality of life." Finally, this appliciation will utilize the strengths of the Free Radial and Radiation Biology Program to translate the clinical evaluation to underlying neural changes. To this end, we will build on emerging evidence that the deleterious effects of chemotherapy may involve the acceleration of degenerative processes such as mitochondrial DNA damage and alterations in oxidative stress that are increasingly associated with neural aging. Therefore this study will also explore the role of mitochondrial deletions as a mechanism that may contribute to brain changes. By exploring the underlying mechanisms for neurodegeneration, specific testable treatments and prevention strategies may ultimately be developed.




Frontal hypometabolism in elderly breast cancer survivors determined by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET): a pilot study.
Authors: Ponto L.L. , Menda Y. , Magnotta V.A. , Yamada T.H. , Denburg N.L. , Schultz S.K. .
Source: International Journal Of Geriatric Psychiatry, 2015 Jun; 30(6), p. 587-94.
PMID: 25176562
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Cognitive features 10 or more years after successful breast cancer survival: comparisons across types of cancer interventions.
Authors: Nguyen C.M. , Yamada T.H. , Beglinger L.J. , Cavanaugh J.E. , Denburg N.L. , Schultz S.K. .
Source: Psycho-oncology, 2013 Apr; 22(4), p. 862-8.
PMID: 22585465
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Practice effects predict cognitive outcome in amnestic mild cognitive impairment.
Authors: Duff K. , Lyketsos C.G. , Beglinger L.J. , Chelune G. , Moser D.J. , Arndt S. , Schultz S.K. , Paulsen J.S. , Petersen R.C. , McCaffrey R.J. .
Source: The American Journal Of Geriatric Psychiatry : Official Journal Of The American Association For Geriatric Psychiatry, 2011 Nov; 19(11), p. 932-9.
PMID: 22024617
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Neuropsychological outcomes of older breast cancer survivors: cognitive features ten or more years after chemotherapy.
Authors: Yamada T.H. , Denburg N.L. , Beglinger L.J. , Schultz S.K. .
Source: The Journal Of Neuropsychiatry And Clinical Neurosciences, 2010 Winter; 22(1), p. 48-54.
PMID: 20160209
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Predicting cognitive change in older adults: the relative contribution of practice effects.
Authors: Duff K. , Beglinger L.J. , Moser D.J. , Paulsen J.S. , Schultz S.K. , Arndt S. .
Source: Archives Of Clinical Neuropsychology : The Official Journal Of The National Academy Of Neuropsychologists, 2010 Mar; 25(2), p. 81-8.
PMID: 20064816
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Practice effects and outcome of cognitive training: preliminary evidence from a memory training course.
Authors: Duff K. , Beglinger L.J. , Moser D.J. , Schultz S.K. , Paulsen J.S. .
Source: The American Journal Of Geriatric Psychiatry : Official Journal Of The American Association For Geriatric Psychiatry, 2010 Jan; 18(1), p. 91.
PMID: 20104658
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Evaluation of older persons with mild cognitive deficits: potential utility of magnetic resonance imaging.
Authors: Schultz S.K. , Magnotta V. , Duff K. , Boles Ponto L.L. , Moser D.J. .
Source: Annals Of Clinical Psychiatry : Official Journal Of The American Academy Of Clinical Psychiatrists, 2008 Oct-Dec; 20(4), p. 204-8.
PMID: 19034752
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