# Alcohol: A Modifiable Risk Factor for Ataxia and Decline in MCI

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $551,488

## Abstract

This application for an administrative supplement is written in response to NOT-AG-17-008: Alzheimer's
Disease and its related Dementias (AD/ADRD), which is targeted for NIH grants that are not focused on
Alzheimer's disease (AD). Our funded parent grant (AA010723), "Alcohol: A Modifiable Risk Factor for Ataxia
and Decline in MCI," is investigating gait and balance instability together with levels of alcohol consumption as
potential contributors to decline in postural stability as occurs in Mild Cognitive Impairment (MCI), often
heralding AD. The supplement proposes to expand our directed search for neural substrates and performance
factors that contribute to stability declines using advanced multi-modal imaging and analysis combined with
innovative gait and stability metrics in men and women with MCI and age- and sex-matched controls with
varying levels of alcohol consumption, from none to meeting criteria for Alcohol Use Disorder (AUD).
We propose to use a specialized MRI analysis protocol (Quantitative Susceptibility Mapping, QSM) to measure
non-heme iron, which accumulates in the brain with age, MCI, AD/ADRD, and AUD. Relevant to this project,
iron concentration is greatest in structures serving motor functions, notably, basal ganglia (globus pallidus,
caudate nucleus, and putamen), substantia nigra, and dentate nuclei of the cerebellum. Age, alcohol, and
disease related accumulation of iron in these brain regions have the potential 1) to disrupt motor performance
involving gait and balance and 2) to attenuate functional connections intersecting with these regions.
Accordingly, we propose expansion of the parent grant to address the following aims:
a) To test regional iron deposition as substrates of selective postural and gait instability metrics in
men and women with and without MCI with varying levels of alcohol consumption, from none to AUD.
b) To determine whether local iron deposition disrupts or attenuates functional connectivity between
subcortical and cerebellar motor substrates and their cortical targets in MCI and how levels of alcohol
consumption contribute to the iron-related disruption and potentially accelerate progression from MCI
to AD/ADRD.
Slowness of gait has been recognized as an early feature of Alzheimer's Disease and its related Dementias.
Although postural instability and gait disturbances may be subtle in MCI, quantitative analysis may reveal
component factors of declining gait that are precursors to the emergence of AD/ADRD. Gait comprises multiple
factors that can be identified and dissociated with our recently devised analysis of videos taken while people
walk. Relevantly, this motor and neuroimaging protocol, which is well-tolerated by our older participants, will be
readily translated to a future proposal to track postural instability in our current cohort of MCI as some progress
to AD/ADRD. Ultimately, we anticipate that identified gait/brain relations may have the sensitivity and specificity
to serve as prodro...

## Key facts

- **NIH application ID:** 10711220
- **Project number:** 3R01AA010723-25S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** EDITH VIONI SULLIVAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $551,488
- **Award type:** 3
- **Project period:** 1996-04-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10711220

## Citation

> US National Institutes of Health, RePORTER application 10711220, Alcohol: A Modifiable Risk Factor for Ataxia and Decline in MCI (3R01AA010723-25S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10711220. Licensed CC0.

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