# Microvascular mechanisms underlying white matter lesions in older adults

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $128,520

## Abstract

PROJECT SUMMARY
This proposal presents a plan for the candidate’s career enhancement that focuses on studying hemodynamic
etiology of white matter lesions (WML) in the context of risk for Alzheimer’s disease (AD). The goal is to
uncover physiological mechanisms that may inform development of therapies for reducing WML-related
cognitive decline in older adults at elevated risk for AD.
Candidate: The candidate is an Instructor of Radiology at Harvard Medical School and Massachusetts
General Hospital. His research interests are to explore relationships between microvascular physiology and AD
by developing novel methods for imaging microvascular function as markers of disease. The candidate’s
academic training has provided a foundation in magnetic resonance imaging (MRI) methods, with a focus in
cerebrovascular diseases. His research efforts thus far have resulted in a publication record, conference
awards, and success in obtaining funding that demonstrate his strong potential to develop into a successful
investigator. However, there are gaps between the candidate’s background in MRI methods development and
his current interests in small vessel disease in aging and dementia. The candidate’s plan for career
enhancement addresses these gaps with training in aging and dementia, small vessel disease, and human
study design. This coursework will be complemented with experimental training that leverages his background
in MRI of microvascular function to bridge his transition to independence.
Research: AD is expected to impact 13.8 million Americans by 2050, necessitating a more complete
understanding of the etiology and the development of markers for diagnosis and progression. Beta-amyloid
plaques and neurofibrillary tangles characterize AD pathology, but WMLs of presumed small vessel origin are
an independent contributor to cognitive decline in AD patients. The high prevalence of WML in patients with AD
suggests that cerebrovascular disease may play an important role in the pathophysiology of AD. However, the
physiological mechanisms contributing to the development of WML remain unclear. A better understanding of
the microvascular physiology associated with the formation of these white matter lesions may inform the
development of therapies aimed at preventing or delaying associated cognitive decline in AD patients. A critical
barrier to understanding relevant physiology is the lack of sensitive methods for noninvasively measuring
microvascular function in white matter. The objective of this work is to apply sensitive MRI protocols at 7 Tesla
for measuring white matter hemodynamics towards answering focused questions regarding hemodynamic
function in older adults at elevated risk for AD. Results will also inform the design of longitudinal human studies
examining the role of promising microvascular markers in stratifying high risk individuals for preventative
therapies aimed at reducing the burden of WML burden-related cognitive decline.

## Key facts

- **NIH application ID:** 10301549
- **Project number:** 1K01AG070318-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Meher R Juttukonda
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $128,520
- **Award type:** 1
- **Project period:** 2021-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301549

## Citation

> US National Institutes of Health, RePORTER application 10301549, Microvascular mechanisms underlying white matter lesions in older adults (1K01AG070318-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10301549. Licensed CC0.

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