# Role of slow waves and sleep apnea in memory and risk for Alzheimer disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $696,482

## Abstract

Project Summary
Alzheimer disease (AD) is the most common neurodegenerative disease and is characterized by the
accumulation of amyloid plaques, composed of amyloid beta (Aβ) peptides. Current consensus is that the AD
pathological process begins decades before clinical symptoms occur. Emerging evidence suggests that sleep
disruption may be an important factor in both the cognitive deterioration of AD and in the progression of
molecular factors, such as the metabolism of Aβ peptides, that promote ultimate plaque deposition and
neurodegeneration. Obstructive sleep apnea (OSA) is the most common sleep disorder in the US and is thought
to exert its pathogenic effects through some combination of sleep fragmentation (SF) and intermittent hypoxia
(IH). A better understanding of the mechanisms by which sleep disruption impacts memory and risk for AD
can stem from evaluating the role of disruption of specific sleep stages and, when such disruption occurs
through OSA, from evaluating the individual contributions of SF and IH. We have strong preliminary evidence
showing that the presence of OSA lowers the age at which individuals experience cognitive decline to mild
cognitive impairment by 10 years, and subjects with OSA show the greatest increases in cerebrospinal fluid
(CSF) levels of Aβ peptides when followed longtidinally. Furthermore, we have preliminary evidence linking
decreases specifically in slow wave sleep (SWS) to both decreased overnight consolidtion of spatial navigational
memory and increases in CSF levels of Aβ42. We have developed a novel model of sleep stage-specific
induction of OSA through continuous positive airway pressure (CPAP) withdrawal in subjects who have severe
OSA and who are fully adherent to CPAP on a nightly basis. By limiting CPAP withdrawal to slow wave sleep
(SWS) through real time EEG monitoring, we can recapitulate severe OSA in SWS only, with negligible OSA in
other sleep stages. This model allows us to address a potential causal role for SWS disruption in the
impairment of spatial navigational memory (Aim 1) and in increasing CSF concentrations of Aβ peptides (Aim
2). By providing supplemental oxygen during the CPAP withdrawal, we can create OSA in which sleep
fragmentation continues to occur while IH is significantly minimized. This model will allow us to address a
second major focus: to differentiate effects of SF and IH on spatial navigational memory (Aim 3) and regulation
of CSF Aβ (Aim 4). To test these ideas, 85 adult subjects (age 25-70) will be recruited to perform brain imaging
and ApoE genotyping and serial tests of spatial navigational memory, morning psychomotor vigilance, a
lumbar puncture (LP) synchronized to their circadian rhythm (by actigraphy). Subjects will be tested in 3
conditions across different nights separated by at least 2 weeks: 1) CPAP held at the therapeutic value
throughout 2) CPAP withdrawn exclusively in SWS and 3) CPAP withdrawn exclusively in SWS with
simultaneous addition of suppleme...

## Key facts

- **NIH application ID:** 10160731
- **Project number:** 5R01AG056682-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** ANDREW W VARGA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $696,482
- **Award type:** 5
- **Project period:** 2017-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160731

## Citation

> US National Institutes of Health, RePORTER application 10160731, Role of slow waves and sleep apnea in memory and risk for Alzheimer disease (5R01AG056682-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10160731. Licensed CC0.

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