As the US population ages, it is increasingly important to understand heterogeneity in cognitive aging including pathologic conditions like Alzheimer?s disease (AD) and cancer-related cognitive decline (CRCD). There is data to suggest that CRCD and AD share important cognitive aging features. The objective of this secondary data analysis project is to test if older breast cancer survivors with CRCD have clinical-pathological features of AD, including AD-pathology biomarker abnormalities, cognitive changes, brain imaging alterations, and similar risk factor profiles. To accomplish this goal, we will use existing de-identified data and banked specimens from the Thinking and Living with Cancer (TLC) study cohort. TLC includes female breast cancer survivors ages 60- 98 years old assessed pre-treatment and annually for up to 60 months and an equal number of contemporaneously assessed non-cancer controls (n=700/group). Consent included future use of data and specimens for new research purposes. Studying older breast cancer survivors is logical since they are already facing cognitive aging, CRCD has been described most often in breast cancer, the survivors are in the age range where non-cancer populations with APOE-?4 develop AD, AD rates are higher in females vs. males, and 35% of TLC survivors already have global cognitive decline based on significantly greater change than the non-cancer controls. Longitudinal TLC data include scores on neuropsychological tests of memory, executive functioning, language, and visuospatial abilities; demographics; AD risk factors; and inflammation markers (IL- 6, TNF-a, IL-8, IL-10, IFNg, CRP). We add to these data by using banked specimens to test plasma AD- pathology biomarkers (A?1-42, tau, p-tau, and neurofilament light chain [NFL]) and danger-associated molecular patterns (DAMPs: A?, S100 proteins, and HMBG1). A sub-set of TLC survivors at Indiana University has baseline and 12-month MRI data using the NIA-funded Indiana Alzheimer?s Disease Center (IADC) protocol. We will complete 24-month imaging of these survivors (n=75) to assess post-acute effects. We will compare TLC survivor results to TLC non-cancer controls and published AD data, including those specific to women.
The aims are to test hypotheses about associations between: 1) CRCD and clinical-pathological features of AD, 2) CRCD and established AD-risk factors, and 3) AD-related inflammatory markers and AD clinical- pathological features in CRCD and explore if inflammation mediates CRCD risk. This research is significant because we are looking at biological mechanisms for two important cognitive aging processes- CRCD and AD. We will advance NIA research goals by elucidating the impact of genetics and inflammatory processes on cognitive aging. This research is significant because cognitive aging has clinically important effects on daily life. We are not aware of any studies comparing CRCD and AD, and none that include an established collaboration of cancer, Alzheimer?s, and geriatrics investigators working together across silos. Overall, this study will move the field forward by determining potential bidirectional mechanisms between CRCD and AD.

Public Health Relevance

Cognitive aging is clinically important in the growing older population because cognitive decline can reduce quality of life, decrease function, and lead to social isolation to conceal deficits. Alzheimer?s disease (AD) and cancer-related cognitive decline (CRCD) are common diseases of cognitive aging, and are the most frequent causes of morbidity and mortality in older individuals. We will use existing de-identified data from older breast cancer survivors to test the hypothesis that CRCD shares common risk factors and clinical-pathological features with AD; the results will provide bidirectional insights into mechanisms, prevention and treatment of AD and CRCD.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Anderson, Dallas
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Georgetown University
Internal Medicine/Medicine
Schools of Medicine
United States
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