# Cognitive Aging, Alzheimers disease, and Cancer-related Cognitive Decline

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2020 · $659,806

## Abstract

ABSTRACT
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 (Aβ1-42, tau, p-tau, and neurofilament light chain [NFL]) and danger-associated molecular
patterns (DAMPs: Aβ, 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 o...

## Key facts

- **NIH application ID:** 10028895
- **Project number:** 1R01AG068193-01
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Jeanne Mandelblatt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $659,806
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028895

## Citation

> US National Institutes of Health, RePORTER application 10028895, Cognitive Aging, Alzheimers disease, and Cancer-related Cognitive Decline (1R01AG068193-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10028895. Licensed CC0.

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