# Developing novel cognitive and neuroimaging markers of early Alzheimers disease pathologies

> **NIH NIH R01** · BROWN UNIVERSITY · 2021 · $738,502

## Abstract

PROJECT SUMMARY
The goal of the proposed study is to develop novel cognitive and neuroimaging markers to detect subtle
cognitive and neural changes in association with beta-amyloid (Aβ) deposition and tau-protein neurofibrillary
tangles (NFT), pathological hallmarks of Alzheimer's disease (AD), among clinically intact older adults. Recent
advances in in vivo positron emission tomography (PET) have significantly increased our awareness of the
presence of Aβ plaques in approximately 20-50% of cognitively normal older adults who are now considered
as preclinical AD. Differentiating healthy older adults from those who are in the preclinical stage of AD,
however, remains to be challenging, in part because behavioral and neural measures that are sensitive and
specific to detect the presence of Aβ plaques in the stage of preclinical AD are largely lacking. Furthermore,
the co-presence of NFT pathology in these individuals makes it difficult to link AD pathologies to specific
cognitive function. Identifying how brain aging and AD pathology affect cognition and the underlying neural
systems would offer more sophisticated behavioral phenotypes and neural markers with clinical utility in aiding
early diagnosis and treatment monitoring that otherwise may remain undetected with traditional
neuropsychological tests. We will recruit 50 healthy young adults and 125 cognitively normal elderly who will
undergo cognitive experimental, neuroimaging, and neuropsychological assessments. Aim 1 will test the
hypothesis that Aβ deposition and NFTs in cognitively normal elderly will differentially impact a set of cognitive
component tasks that disproportionately tax frontoparietal and medial temporal lobe functions. Aim 2 will test
that Aβ deposition and NFTs differentially affect brain activation and connectivity patterns measured by
structural and functional MRI during cognitive tasks that use a gradient degree of frontoparietal and medial
temporal lobe function. Aim 3 will compare the sensitivity and specificity in detecting the effect of Aβ deposition
and NFTs on cognition between cognitive component tasks and traditional neuropsychological assessments. A
successful completion of the aims will elucidate the mechanistic link between AD pathologies and cognitive
consequences in the early stage of the disease and contribute to novel behavioral and neuroimaging markers
of early AD. The developed cognitive task battery has a potential to be developed as a screening test for the
presence of AD pathologies in a non-invasive, more accessible, and more affordable manner for clinically
intact older adults.

## Key facts

- **NIH application ID:** 10260635
- **Project number:** 5R01AG068990-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Hwamee Oh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $738,502
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260635

## Citation

> US National Institutes of Health, RePORTER application 10260635, Developing novel cognitive and neuroimaging markers of early Alzheimers disease pathologies (5R01AG068990-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10260635. Licensed CC0.

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