# Slow-wave sleep enhancement in those at risk for Alzheimer's disease: Links with memory, excitotoxicity, and plasma A-beta

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $695,715

## Abstract

Dementia caused by Alzheimer’s disease affects approximately 5.6M adults over age 65, with costs expected
to rise from $307B to $1.5T over the next 30 years. Behavioral interventions have shown promise for mitigating
neurodegeneration and cognitive impairments. Sleep is a modifiable health behavior that is critical for cognition
and deteriorates with advancing age and Alzheimer’s disease. Thus, it is a priority to examine whether
improving sleep modifies Alzheimer’s disease pathophysiology and cognitive function. Our research suggests
that deeper, more consolidated sleep is positively associated with memory and executive functions and
networks that underlie these processes. Our preliminary studies confirm that time-in-bed restriction
interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest
that increases in SWA are associated with improved cognitive function. SWA reflects synaptic downscaling
predominantly among prefrontal connections. Downscaling of prefrontal connections with the hippocampus
during sleep may help to preserve the long-range connections that support memory and cognitive function. In
pre-clinical Alzheimer’s disease, hyperactivation of the hippocampus is thought to be excitotoxic and is shown
to leave neurons vulnerable to further Aβ deposition. Synaptic downscaling through SWA may mitigate the
progression of Alzheimer’s disease through these pathways. The proposed study will behaviorally increase
sleep depth (SWA) through four weeks of time-in-bed restriction in older adults characterized on Aβ deposition
and multiple factors associated with Alzheimer’s disease risk. We will examine whether behaviorally enhanced
SWA reduces hippocampal hyperactivation, leading to improved task-related prefrontal-hippocampal
connectivity, plasma Aβ levels, and cognitive function. This research addresses whether a simple, feasible,
and scalable behavioral sleep intervention improves functional neuroimaging indices of excitotoxicity,
Alzheimer’s pathophysiology, and cognitive performance.

## Key facts

- **NIH application ID:** 10436846
- **Project number:** 5R01AG068001-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kristine Ann Wilckens
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $695,715
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436846

## Citation

> US National Institutes of Health, RePORTER application 10436846, Slow-wave sleep enhancement in those at risk for Alzheimer's disease: Links with memory, excitotoxicity, and plasma A-beta (5R01AG068001-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436846. Licensed CC0.

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