# Quantitative Neuroimaging Assessment of White Matter Integrity in the Context of Aging and AD

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $476,720

## Abstract

PROJECT SUMMARY
 Although the single most significant risk factor for developing Alzheimer's disease (AD) is age, the
neurobiological processes underlying the transition from normal aging to AD are not well understood. The loss
of white matter (WM) integrity is known to occur in normal aging and it is hypothesized that an accelerated loss
of WM integrity is one mechanism for the transition from normal aging to AD. Indeed, the age-related loss of
WM integrity in late-myelinating association regions in the frontal and temporal lobes are the same neocortical
regions most vulnerable to the development of AD pathology.
 In direct response to announcement PAR-15-357: Understanding Alzheimer's Disease in the Context of
Brain Aging, we propose to investigate the hypothesis that changes in brain WM integrity are key mechanisms
by which a normal aging brain can transition to AD. Our group has recently developed MRI-based biomarkers
that are sensitive to subtle changes in WM integrity. These biomarkers consist of quantitative WM tract integrity
(WMTI) metrics that characterize specific tissue properties such as axonal density and myelin integrity. Using
these WMTI metrics, we have differentiated normal controls from patients with MCI, indicating that WM
changes occur early in the AD disease process. We have also demonstrated that these WMTI metrics may be
useful even earlier in the process by differentiating between normal controls with and without hippocampal
atrophy. Thus, the overall hypothesis of this project is that an accelerated loss of WM integrity is evident in the
transition from normal aging to AD, and by combining biomarkers of WMTI, degree of Aβ accumulation,
neurodegeneration (i.e. hippocampal and cortical atrophy), and cognitive function, we will be able to stratify
cognitively intact older adults for risk of conversion to MCI/AD.

## Key facts

- **NIH application ID:** 10170186
- **Project number:** 5R01AG054159-05
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Andreana Benitez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $476,720
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170186

## Citation

> US National Institutes of Health, RePORTER application 10170186, Quantitative Neuroimaging Assessment of White Matter Integrity in the Context of Aging and AD (5R01AG054159-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10170186. Licensed CC0.

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