# Novel diffusion-weighted MRI assessment of cortical microstructural changes and their relationship to amyloid, tau and cognition in aging and Alzheimer's disease.

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $223,750

## Abstract

ABSTRACT
Alzheimer’s disease (AD) has a long presymptomatic period characterized by the co-existence of several
pathophysiological processes leading to overt neuronal damage. Despite the well-established findings of brain
atrophy in the later (symptomatic) stages of AD, the trajectory of these structural changes along the AD
continuum remains controversial. Importantly, recent studies have demonstrated evidence for changes in the
microstructural properties of the brain tissue in the cortical mantle occurring already in the preclinical stage of
the disease, and these changes have been suggested to play an important role in the early pathophysiology of
AD. However, the impact of these early microstructural changes on disease progression remains understudied,
mainly due to the limited methodological approaches to study them in the human brain. The recent advent of a
novel methodological neuroimaging approach using diffusion-weighted imaging (DWI) technique, has made it
possible to quantifying microstructural changes by means of cortical mean diffusivity in the grey matter.
Previous studies using this technique have demonstrated microstructural changes in preclinical AD as well as
presymtomatic mutation carriers of autosomal dominant AD, support the notion that microstructural changes
are occurring early in the disease process. However, the mechanism by which early regional Aβ deposits in the
brain are related to microstructural changes, and how their interactions may lead to further disease progression
remains unknown. In this R21 proposal we will validate and further develop advanced DWI MRI methods for
detecting the microstructural changes that accompany AD. By using multimodal, state-of the-art methods
the overall objective of this proposal is to visualize the interplay between early microstructural alterations and
pathological changes (extracellular Aβ and tau) across early preclinical stages of AD as well as its relation to
cognition. Specifically, using data from an existing NIA-funded, rich multi-modality dataset (Harvard Aging
Brain Study) of cognitively normal older individuals the proposed work will determine the cross-sectional
regional relationship of microstructural changes with amyloid Aβ burden, as measured with PiB-PET (Aim 1).
Furthermore, we will use longitudinal data to determine whether microstructural changes at baseline portends
increased tau deposition, as measured with T807 (Aim 2), and lower cognition (Aim 3) at follow up, and
whether Aβ modifies these relationships. The proposed work may provide critical information to improve our
understanding of the mechanistic underpinnings of how microstructural changes are linked to AD pathology, as
well as their effect on brain function. As a consequence, the findings could substantially improve our
understanding of the evolution of AD etiology and may contribute to the clinical diagnosis of the disease.

## Key facts

- **NIH application ID:** 9986598
- **Project number:** 5R21AG064348-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Patrizia Vannini
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $223,750
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986598

## Citation

> US National Institutes of Health, RePORTER application 9986598, Novel diffusion-weighted MRI assessment of cortical microstructural changes and their relationship to amyloid, tau and cognition in aging and Alzheimer's disease. (5R21AG064348-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9986598. Licensed CC0.

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