# Glutamate Chemical Exchange Saturation Transfer (GluCEST) Imaging in Cognitive Aging

> **NIH NIH R56** · UNIVERSITY OF PENNSYLVANIA · 2020 · $532,865

## Abstract

Healthy older adults (HOA) confront complex and life-changing decisions in the face of declining neural
resources. Changes in aged brains include shrinkage of neurons and their projections in several areas, such
as the neocortex, hippocampus and substantia nigra.1 These age-related structural brain changes, typically
measured using in vivo techniques (e.g. MRI), reflect cellular changes. Glutamate (Glu) is a key molecule in
cellular metabolism, the most abundant excitatory neurotransmitter in the mammalian nervous system, and the
principal neurotransmitter of cortical efferents.2,3 Alterations in brain Glu likely contribute to the neural
mechanisms underlying age-related declines in behavioral and cognitive functions.4 Yet, only a few studies4-11
have investigated age-related changes in brain Glu, in vivo, during healthy aging. Most of these have used
standard techniques and as a result our understanding of the role that brain Glu has in typical and atypical
aging remains limited. Here, I aim to fill significant gaps in the field, by 1) assessing brain Glu using a novel
magnetization transfer technique—Glutamate Chemical Exchange Saturation Transfer (GluCEST)—on an
ultra-high field 7T MRI scanner, enables the measurement of brain Glu across the cerebrum in humans.12; 2)
assess cognitive performance using a highly sensitive computerized neurocognitive battery (Penn
Computerized Neurocognitive Battery (CNB)); and 3) explore the possibility of aging biotypes based upon age-
related changes in brain glutamate.
 Here, we propose to investigate alterations in brain glutamate in 100 HOA (60-85 years of age) using
GluCEST 7T MRI and relate alterations in brain Glu to age-related changes in cognitive functioning, including,
memory, and executive function. Moreover, we will contrast age-related patterns with data from young adults
(18-30 years of age). Finally, we leverage data from a large consortium, iSTAGING (directed by Co-
Investigator Davatzikos), to employ recently developed machine-learning techniques (e.g. HYDRA13), to
classify subgroups of older adults based upon unique patterns of brain structure associated with typical,
atypical and resilient aging. These subtypes will be applied within our sample and patterns of brain glutamate
can then be measured within these subtypes. The proposed studies will provide more specific and sensitive in
vivo measurements of brain glutamate in HOA. This proposal will enable testing of specific hypothesis about
the regional distribution of brain Glu, its relation to aging, and its contribution to cognitive functioning in aging.
As such, these studies can provide crucial preliminary data for longitudinal studies in healthy and pathological
aging by targeting a specific neural mechanism associated with cognition and disease progression.

## Key facts

- **NIH application ID:** 10241606
- **Project number:** 1R56AG066656-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** DAVID REID ROALF
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $532,865
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241606

## Citation

> US National Institutes of Health, RePORTER application 10241606, Glutamate Chemical Exchange Saturation Transfer (GluCEST) Imaging in Cognitive Aging (1R56AG066656-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241606. Licensed CC0.

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