# Neuroimaging of Visual Attention in Aging

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $389,163

## Abstract

The parent grant for this administrative supplement, R01 AG039684, is designed to investigate
structural and functional brain connectivity, and cognitive performance, in the context of healthy aging. In this
administrative supplement application, in response to NOT-AG-20-008, we propose to apply the imaging
techniques, developed in the parent R01, to develop an additional focus on Alzheimer's disease (AD). The
overall goal is to investigate the potential value of regional brain iron as a novel biomarker of AD. Currently,
postmortem histology is needed for a definite determination of AD, However, validated, in vivo biomarkers
from cerebrospinal fluid (CSF) and neuroimaging exist that are proxies for the neuropathologic changes and
can provide a diagnosis of probable AD. Because these biomarkers are either relatively invasive (e.g., lumbar
puncture) or involve radioactivity exposure during imaging, a critical need exists for less invasive and widely
available biomarkers that may be predictive of AD.
 Non-heme iron, which is the most abundant metal in the brain, is a contributor to essential
neurobiological processes, including oxygen transportation, mitochondrial respiration, myelin synthesis, and
neurotransmitter synthesis and metabolism. Excess iron, however, promotes spontaneous release of highly
neurotoxic free iron, which leads to the harmful formation of highly reactive radical species, thus drastically
exacerbating oxidative stress and neuronal death. Postmortem histological studies have demonstrated
increases in the level of iron within deep gray matter and neocortical regions during aging and
neurodegenerative disease, including AD and related forms of dementia. The regional distribution of iron co-
localizes with the plaques and neurofibrillary tangles definitive of AD. Magnetic resonance imaging (MRI) can
estimate iron deposition through analyses of the susceptibility data in diffusion weighted imaging (DWI),
without obtaining CSF or using a radioactive imaging tracer. Previous MRI studies suggest that AD is
associated with increased iron in deep gray matter and cortical regions, as well as a decline in functional brain
connectivity. These previous studies, however, have typically been conducted at a conventional level of spatial
resolution and have not as yet demonstrated a relation of iron to AD-related decline in functional connectivity.
 In this project, we propose to use high-resolution (sub-millimeter) quantitative susceptibility mapping
(QSM) to estimate regional brain iron in 30 individuals diagnosed with probable AD and 30 healthy, age-
matched controls. The increased spatial resolution will allow the estimation of iron across cortical depth. We
will characterize AD-related differences in brain iron within deep gray matter and cortical regions (Aim 1) and
test for the potential influence of brain iron on AD-related decline in functional brain connectivity (Aim 2).
These aims are within the scope of the parent R01 but develop a n...

## Key facts

- **NIH application ID:** 10120059
- **Project number:** 3R01AG039684-08S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** David J. Madden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,163
- **Award type:** 3
- **Project period:** 2018-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120059

## Citation

> US National Institutes of Health, RePORTER application 10120059, Neuroimaging of Visual Attention in Aging (3R01AG039684-08S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10120059. Licensed CC0.

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