# Neural substrates of diffusion imaging in cognitively aging rhesus monkeys

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $833,908

## Abstract

7. Abstract.
 The ability to identify and follow-up neurobiological changes that occur during brain maturation and aging is
not only fundamental to our understanding of cognition, but is also crucial for clinical studies that focus on
either neurodevelopmental or neurodegenerative disorders, including clinical trials. While post-mortem studies
provide data that are well characterized in terms of localized histological changes, these data can be limited
due to their cross sectional nature and small samples sizes. In contrast, non-invasive in vivo imaging allows for
the collection of longitudinal data in much larger populations, and is a more powerful tool to investigate life
span trajectories of brain maturation and aging.
Recent developments in neuroimaging have provided evidence for the relationship between imaging changes
and cognitive aging in monkeys, and humans. Unfortunately, the cellular underpinnings of cognitive age are a
subject of debate and hence the biological specificity of available imaging measures is not well established.
More alarming, while older imaging measures still lack thorough validation, newer “more specific” measures
that are being constantly introduced into clinical research are even further from validation. Over the past
funding period, we have worked with a large repository of histological, cognitive and imaging legacy data from
cognitively aging rhesus monkeys, testing the hypothesis that neuroinflammation and myelin degeneration play
crucial roles in cognitive aging, and that neuroimaging biomarkers can reflect those biological processes.
We propose to further our work in this direction, by proposing translational experiments that will include 1).
acquiring new, high resolution “Human Connectome Project (HCP)” compatible imaging data, 2). Expand our
neuroimaging by adding neuroinflammation- and myelin-specific PET radioligands, 3). Develop neuroimaging
white matter-specific biomarkers of mild cognitive impairment- a risk factor for Alzheimer’s disease, and 4).
Investigate biological underpinnings of sex differences in aging. This is enabled by a collaboration of three PIs,
with unique and complementary expertise in MRI imaging, morphometry, neuroanatomy,
immunohistochemistry and cognitive aging, and will be further facilitated by acquiring and analyzing behavioral,
imaging, blood and post mortem data from a cohort of 24 rhesus monkeys of both sexes, 8 young adults (4
males and 4 females) and 16 old adults (8 males and 8 females, half diagnosed with mild cognitive impairment
(MCI)).
The results of this proposed study will greatly impact our understanding of aging processes and their
mechanisms and provide tissue validated understanding of imaging measures that can be applied to studies of
normal human aging as well as many neurodevelopmental and neurodegenerative diseases of the central
nervous system.

## Key facts

- **NIH application ID:** 10160747
- **Project number:** 5R01AG042512-08
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Marek Kubicki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $833,908
- **Award type:** 5
- **Project period:** 2013-09-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160747

## Citation

> US National Institutes of Health, RePORTER application 10160747, Neural substrates of diffusion imaging in cognitively aging rhesus monkeys (5R01AG042512-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10160747. Licensed CC0.

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