# Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2022 · $552,874

## Abstract

Identifying Associations between Brain Iron, Neurocognitive Networks and
Protective Factors
Alzheimer’s disease (AD) involves accumulation of pathological levels of amyloid-beta (Aβ)
and phospho-tau proteins. However, a significant proportion of individuals with AD pathology
do not have clinical AD, indicating contributions of other factors. Novel in-vivo measures are
required to track other factors contributing to AD-related cognitive declines. Increasing
evidence suggests that age-related accumulation of brain iron and its correlates contribute to
the manifestation of memory declines. Our recent neuroimaging results suggest that high
brain iron concentration, measured with in vivo quantitative susceptibility mapping (QSM), is
associated poor connectivity within brain memory networks. This proposal seeks to identify
associations between QSM-based iron concentration and neurocognitive changes toward a
goal of improving AD biomarkers. We will also define the interplay between QSM-based iron
signal, AD pathology, inflammatory markers on cognitive declines. Finally, we will test the
possibility that brain iron accumulation may be slowed by an antioxidant rich diet. We
propose to study 140 healthy older adults using neuroimaging measures including fMRI and
QSM, measures of CSF and plasma Aβ, p-tau and t-tau and inflammatory markers.
Additional structural neuroimaging measures will include regional volumes, FLAIR imaging
for quantification of WMH volumes and diffusion tensor imaging for quantification of
regionally distributed white matter connectivity. A subset of participants will be complete the
same CSF and imaging measures approximately 3 years later. We aim to identify (1) effects
of QSM-based iron signal on functional and structural brain networks supporting cognition;
(2) associations between brain iron, inflammatory markers, AD pathology and cognitive
declines and; (3) modifiers of brain iron or its effects on cognition. We will test hypotheses
that high QSM-based brain iron is associated with low connectivity in memory circuits
independently of AD pathology but may and synergistically interacts with AD over time. We
will also test the hypothesis that reserve factors will offset the effects of brain iron on
cognitive functions via mechanisms of brain maintenance or plastic functional brain
reorganization of large-scale brain functional networks in some older adults.

## Key facts

- **NIH application ID:** 10395546
- **Project number:** 5R01AG068055-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** BRIAN Timothy GOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $552,874
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395546

## Citation

> US National Institutes of Health, RePORTER application 10395546, Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors (5R01AG068055-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10395546. Licensed CC0.

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