# Imaging Advancements in Small Vessel and CSF Flow Pathophysiology of Pre-clinical Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $736,171

## Abstract

Project Summary/Abstract:
There is a well-established association between small vessel disease (SVD, microangiopathy) and Alzheimer's
disease (AD). The underlying mechanisms for associations between small vessels and the AD cascade
remain unclear. Some of the association between SVD and AD is due to the cumulative cognitive burden from
independent pathologies (AD and SVD) leading to early manifestation of the clinical syndrome of AD. It is
becomingly recognized that another way in which SVD and AD are related is through bi-directional interaction
at molecular and cellular levels: e.g., inflammatory factors associated with Aβ plaques contribute to SVD.
Furthermore, an emerging hypothesis is that decreased pulsatility of small arterioles decreases cerebral spinal
fluid (CSF) clearance of amyloid, putting someone at risk of AD. A better understanding of the underlying
mechanisms relating SVD and AD is especially important as it can identify prevention and treatment targets.
 This proposed transdisciplinary (Multi-PI) proposal aims to develop advanced MRI methods (hardware,
acquisition, and analysis) with 7T human imaging and study the pathways linking small vessel and CSF flow
pathophysiology to AD. It will be achieved through a consortium consisting of expertise at 1) U. of Pittsburgh -
MRI acquisition and analysis-, and AD; 2) FDA -RF-heating matters in relation guidelines-; 3) U. of Minnesota -
MRI acquisition-; 4) Quality Electrodynamics Inc. (QED) -integration of patient friendly hardware-; and Montreal
Neurological Institute -MRI analysis-. We will examine small vessel morphology, cerebrovascular reactivity
(CVR), and CSF flow, all of which are inter-related components in AD pathophysiology. For instance, small
vessel lesions (in part due to amyloid angiopathy) may disrupt CVR, and consequently interfere with Aβ
clearance.
 The study is designed as a prospective observational study of older adults without dementia: 30
amyloid positive, and 30 amyloid negative (n = 60). We will leverage two ongoing studies (RF1AG025516 &
R01AG052446) of AD pathology for recruitment, clinical characterization and PET imaging. Individuals are
scanned at baseline (Aim 1) using current state of the art technology. Throughout we will work on MRI
development (Aim 2). At 2-year follow up individuals will be scanned again with the same protocol as at
baseline, and will also undergo scanning with the newly developed technology (Aim 3).
 In summary, this study develops, applies and validates advanced imaging of small vessel morphology,
CVR, and CSF flow and other traditional MRI biomarkers to characterize pre-clinical AD, and potentially
identify targets for prevention and/or treatment. The proposal takes advantage of recent and proposed
advances in a timely and recently FDA-approved technology (7T human MRI) and collaborations between: a)
scientists, engineers, and clinicians; b) leading 7T human MRI centers and a coil company; and c) a
governmental regulatory agency.

## Key facts

- **NIH application ID:** 10111445
- **Project number:** 5R01AG063525-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** HOWARD J AIZENSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $736,171
- **Award type:** 5
- **Project period:** 2019-04-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111445

## Citation

> US National Institutes of Health, RePORTER application 10111445, Imaging Advancements in Small Vessel and CSF Flow Pathophysiology of Pre-clinical Alzheimer's Disease (5R01AG063525-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10111445. Licensed CC0.

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