# Experimental sleep fragmentation and cognition in aged marmosets

> **NIH NIH R21** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $239,250

## Abstract

SUMMARY
 Elderly people frequently experience sleep disturbances, which contribute to age-related cognitive
decline and are thought to be a core component of Alzheimer's disease (AD) and its pathophysiology. However,
whether sleep disturbances cause cognitive impairment and neuropathology in AD remain unclear. Indeed
human studies are unable to determine whether sleep disturbances precede or follow the development of AD
pathology. Identifying the precise sequence of events linking sleep fragmentation and disease progression is a
crucial step in better understanding the etiology of AD and identifying new therapeutic targets. Studies in animal
models are needed to investigate this issue. Rodents are useful to identify basic mechanisms underlying the
relationships between sleep and brain function, but also have limitations due to substantial differences from
humans in sleep, cognitive and brain aging phenotypes. Using a more translational animal model with regards
to sleep, cognitive function and neuropathology would likely provide critical new insights into the role of sleep
disturbances in driving AD. The common marmoset (Callithrix jacchus) is ideally suited as such a model. This
diurnal nonhuman primate exhibits monophasic sleep, shows age-related decline in several cognitive domains,
and possesses two hallmarks of AD neuropathology, amyloid-β deposition and accumulation of
hyperphosphorylated tau proteins. In addition, its short lifespan of about 10-12 years is ideal for longitudinal
studies. Marmosets will be fitted with an actigraphy device to monitor sleep/wake patterns. The monkeys will be
trained on a battery of cognitive tasks administered on touchscreens in their home cage. After baseline recording
of sleep and cognitive performance, they will be randomly assigned to a sleep fragmentation (SF) or undisturbed
sleep (control) group. The SF group will be chronically exposed to periods of disrupted sleep designed to mimic
fragmented sleep in AD patients, whereas the control group will be kept undisturbed. Changes in physiology and
cognitive function will be assessed throughout the experiment. The proposed study should validate the marmoset
as a translational preclinical model for future studies focusing on the role of SF on AD neuropathology. The
availability of such a model will be crucial for identifying preventative or therapeutic strategies that are clinically
relevant.

## Key facts

- **NIH application ID:** 10300344
- **Project number:** 1R21AG074251-01
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Agnes Lacreuse
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $239,250
- **Award type:** 1
- **Project period:** 2021-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10300344

## Citation

> US National Institutes of Health, RePORTER application 10300344, Experimental sleep fragmentation and cognition in aged marmosets (1R21AG074251-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10300344. Licensed CC0.

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