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

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2023 · $313,672

## Abstract

The goal of the parent grant is to study heterogeneity in cognitive aging and relationships between cancer-related
cognitive decline (CRCD) and Alzheimer’s disease related dementias (ADRD). The broad research question is
whether CRCD is the result of damage due to the cancer and its therapies that accelerate an underlying early
ADRD or damage to similar systems as are involved in ADRD. To address this question we are testing ADRD
plasma biomarkers and using the results to test the overarching hypothesis that breast cancer survivors ages
60+ with CRCD will have more plasma ADRD-pathology biomarker abnormalities than survivors with no
cognitive abnormalities or contemporaneously assessed non-cancer controls. The originally proposed
ADRD biomarkers in the parent grant were Aβ1-42, p-tau and neurofilament light chain [NfL]. These assays were
planned in a collaborating federal laboratory where the director has left the institution. In the interim, Dr. Jeff
Dage, a leading expert in plasma ADRD biomarkers, joined Indiana University (home of MPI Saykin) and the
NIA National Centralized Repository for Alzheimer’s and Related Dementias (NCRAD). During the timeframe of
this project there have also been significant new breakthroughs in the field of blood-based biomarkers for AD.
Measures of Aβ42 and Aβ40 (reported as the 42/40 ratio), P-tau and neurofilament light chain (NfL) are now
being used in clinical trials to screen for patients with AD pathology and monitor pharmacodynamic responses
to new drugs. Additionally, a marker of reactive astrocytes, GFAP, has been shown to be elevated in response
to amyloid pathology in the earliest stages of AD. These breakthroughs have been possible due to advances in
the precision of the plasma biomarker assays, although this has also been accompanied by increased costs
since the time of parent grant submission. With these rapid changes in the field, cost escalations and the
implementation of the NIA NCRAD laboratory, this supplement will: 1) take advantage of the opportunity to move
biomarker testing to the NCRAD laboratory, 2) use the supplemental funds to modify our assays to match the
most advanced biomarkers in the field (Aβ1-42, Aβ1-40, P-tau181, NfL, and GFAP [new markers bolded]), and
3) expand the number of longitudinal samples that can be tested from two time points (n=617 samples) to a
baseline sample and two longitudinal follow-up time points (n=817 samples). Responding to changes in the field
that were not anticipated at the time of our parent grant submission will allow us to expand the parent grant aims
to address new research questions in a robust, up-to-date manner with more sensitive assays, including use of
prespecified cutoffs being established for P-tau181 in the NCRAD lab and comparison of the cancer survivor
and control results to NCRAD standards. Additionally, because TLC participants were cognitively normal at
baseline, adding testing of more longitudinal specimens will allow us to better unders...

## Key facts

- **NIH application ID:** 10715609
- **Project number:** 3R01AG068193-04S1
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Jeanne Mandelblatt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $313,672
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10715609

## Citation

> US National Institutes of Health, RePORTER application 10715609, Cognitive Aging, Alzheimers disease, and Cancer-related Cognitive Decline (3R01AG068193-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10715609. Licensed CC0.

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