# New approach to studying white matter aging: symmetric multimodal fusion of MRI techniques targeting different biophysical properties of white matter

> **NIH NIH R21** · COLORADO STATE UNIVERSITY · 2022 · $182,720

## Abstract

DESCRIPTION
One of the missing pieces of the puzzle towards development of successful treatments against
cognitive decline and Alzheimer’s Disease and Related Dementias (ADRD) may be
understanding of the white matter (WM). For many years, WM aging has been studied almost
solely using diffusion MRI (dMRI), and predominantly with diffusion tensor imaging. The
limitations of dMRI have lead to inconsistent associations of WM integrity with cognition and
brain function, and an underappreciation of the role of WM in adult neuroplasticity. The goal of
this proposal is to provide a new multimodal approach for studying WM microstructure in living
humans. Our approach combines several advanced quantitative MRI techniques sensitive to
different biophysical properties of myelin and axons. As no single MRI technique – even the
most advanced – can fully characterize WM tissue, we will use symmetric fusion analysis to
capitalize on the strengths and overcome the limitations of each technique. Specifically, we will
use the multiset Canonical Correlation Analysis with joint Independent Component Analysis
(mCCA+jICA) to extract modality-shared and modality-unique independent components (IC)
differentiating the WM of younger from older adults. Our sample will include cognitively and
neurologically healthy younger (n=35, 20-30y) and older adults (n=50 60-80y). The 45min-long
scan will include Neurite Orientation Density and DIspersion Imaging to quantify axonal density,
fiber orientational dispersion, and extracellular volume, a T1-based myelin water imaging,
sensitive to water trapped in myelin lipid bilayers, and quantitative magnetization transfer,
sensitive to the exchange of magnetization with myelin macromolecules. Aim 1 will test whether
the multimodal approach confirms the selective vulnerability to aging in late-developing WM
regions. Aim 2 will test whether the multimodal measure of age-related myelin and axonal loss
correlates with memory, processing speed, executive function and fluid abilities, measured with
the Virginia Cognitive Aging Project battery and the NIH Toolbox®. Exploratory analyses will test
sex differences in the above aims. Together, our novel multimodal approach will lead to a more
robust and unbiased characterization of the aging WM microstructure and provide new evidence
for hotly debated models of cognitive aging. Once established, our approach will be validated in
animal models of cognitive decline, extended to more diverse samples, and combined with
fMRI. Our ultimate aim is to identify new WM targets for treatments for ADRD, to improve
diagnosis of pre-symptomatic dementia to allow early interventions, and to identify protective
and risk factors for WM aging.

## Key facts

- **NIH application ID:** 10489724
- **Project number:** 5R21AG068939-02
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Agnieszka Burzynska
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,720
- **Award type:** 5
- **Project period:** 2021-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489724

## Citation

> US National Institutes of Health, RePORTER application 10489724, New approach to studying white matter aging: symmetric multimodal fusion of MRI techniques targeting different biophysical properties of white matter (5R21AG068939-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10489724. Licensed CC0.

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