# White Matter Metabolism in the Context of Aging, White Matter Hyperintensities and Alzheimer's Disease

> **NIH NIH RF1** · WASHINGTON UNIVERSITY · 2022 · $2,287,856

## Abstract

ABSTRACT
White matter hyperintensities (WMH) are ubiquitous in the aging brain. Prevailing theories implicate
arteriosclerosis and endothelial dysfunction followed by ischemic and hypoxic injury as a cause, but factors that
resist or modify these mechanisms are unknown. Animal studies show that glycolysis is a principal metabolic
feature of normal white matter and protective against mitochondrial failure. However, white matter glycolysis has
been understudied in in vivo human studies and particularly in the context of WMH. Our laboratory has developed
methods, now on a state-of-the-art PET scanner, to quantitatively measure brain glycolysis using multiple
radiotracers, including 15O radiotracers to measure cerebral oxygen consumption (CMRO2), cerebral blood flow
(CBF) and oxygen extraction fraction (OEF), and 18FDG to measure total glucose use (CMRglc), from which we
can derive the rate of aerobic glycolysis (AG). Here we propose to apply these methods to provide gold-standard
quantitative estimates of normal human white matter metabolism, and to specifically investigate white matter
glycolysis in the context of WMH. In our first two aims, we will compare the topography of metabolic PET
measurements to MRI measurements of white matter microstructure and WMH, both in healthy adults without
WMH and in adults with WMH. In our third aim, we will analyze longitudinal MRI imaging data in a cohort of
adults who have already undergone metabolic PET in our prior and ongoing studies on an older scanner, to test
the hypothesis that relative differences in white matter glycolysis will predict subsequent WMH development and
progression. Moreover, we will explore potential relationships between neurodegenerative pathology and WMH,
which we hypothesize occurs due to effects of the aforementioned pathology on white matter metabolism,
thereby reducing its resilience to WMH.

## Key facts

- **NIH application ID:** 10444238
- **Project number:** 1RF1AG073210-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Manu S Goyal
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,287,856
- **Award type:** 1
- **Project period:** 2022-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444238

## Citation

> US National Institutes of Health, RePORTER application 10444238, White Matter Metabolism in the Context of Aging, White Matter Hyperintensities and Alzheimer's Disease (1RF1AG073210-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10444238. Licensed CC0.

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