# Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer’s Disease

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $820,753

## Abstract

Title: Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer's Disease
 Though changes in cognition are the most salient features of Alzheimer's disease (AD), subtle
changes in sensation and motor function occur early in the course of AD and might serve as
biomarkers and provide clues as to the cascade of events leading to progressive disability. We will
perform baseline (n = 135) and 3-year f/u evaluations (n = 60) in an ongoing study using the Human
Connectome Project (HCP) protocol of persons of Mexican descent with and at-risk for autosomal
dominant (ADAD) and late-onset AD (LOAD) in order to achieve the following specific aims:
Specific Aim 1a) To define the underlying cause and mechanisms of gait abnormalities in ADAD and
LOAD, we will characterize motor and gait function using the NIH toolbox, the HCP imaging protocol,
and tau PET imaging with flortaucipir.
Specific Aim 1b) To characterize the onset and course of cortical hyperexcitability in ADAD and LOAD
using single-pulse TMS.
Specific Aim 2a) To characterize clinically relevant visual deficits in persons with and at-risk for ADAD
and LOAD using standardized functional measures including logMAR based visual acuity, contrast
sensitivity, as well as low and high contrast reading speed.
Specific Aim 2b) To define the underlying etiology of visual deficits by performing high-resolution, in-
vivo imaging of central and peripheral visual pathway structures including retinal nerve fiber layer
(RNFL), retinal capillary density, volume of optic nerve/chiasm and the lateral geniculate nucleus (LGN)
and connectivity using the HCP.
Specific Aim 3) To characterize deficits in olfaction occurring in persons with and at-risk for ADAD and
LOAD, we will assess olfaction using the University of Pennsylvania Smell Identification Test (UPSIT)
and relate this to tau pathology and connectivity in the olfactory system measured using the HCP.
Comprehensive characterization of motor and sensory changes in ADAD and LOAD could identify
biomarkers for diagnosis, prognosis, and therapeutics targets in the management of the disease.
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## Key facts

- **NIH application ID:** 10320928
- **Project number:** 5R01AG062007-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** JOHN M RINGMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $820,753
- **Award type:** 5
- **Project period:** 2019-02-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320928

## Citation

> US National Institutes of Health, RePORTER application 10320928, Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer’s Disease (5R01AG062007-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320928. Licensed CC0.

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