# Relationships between local and global mechanisms of sleep apnea, Alzheimer's disease biomarkers, and memory impairment in cognitively asymptomatic older adults

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $127,254

## Abstract

Project Summary/Abstract
Epidemiologic evidence has established obstructive sleep apnea (OSA) as a risk factor for Alzheimer’s disease
(AD). However, the mechanisms of this increase in AD risk remain unclear. Three potentially AD-relevant clinical
features of OSA include severity of hypoxemia, global sleep fragmentation, and local deficits in memory-relevant
sleep oscillations, i.e. slow waves and sleep spindles. These clinical features of OSA have been independently
linked to amyloid and tau burden and accumulation, medial temporal lobe (MTL) degeneration, and MTL-
dependent memory impairment—all hallmark biomarkers of AD. However, it remains unclear how each of these
features relate to AD pathophysiology or MTL-dependent memory decline in patients with OSA. The overarching
research objective of this proposal is to address these unknowns. The proposed specific aims are to determine
whether distinct global and local OSA features are associated with 1) cortical amyloid burden, 2) MTL tau burden,
and 3) degeneration of specific MTL brain circuits supporting multiple forms of memory known to depend on
sleep and be vulnerable to AD pathophysiology. The proposed aims will be supported by leveraging existing
resources, and collecting high density electroencephalography (hdEEG, 256 channels) sleep recordings in
cognitively normal older adults (60-85 years) undergoing positron emission tomography (PET) to assess amyloid
and tau burden, as well as ultrahigh resolution magnetic resonance imaging (uhr-MRI) of MTL structure. The
proposed study will therefore capitalize on an opportunity to examine how OSA relates to AD pathological
burden, MTL structure and function, and memory in an unprecedented level of detail and breadth. This is
congruent with both my short and long-term career goals. Specifically, I plan to generate research proposals
seeking funding to uncover the impact of distinct forms of sleep disturbance on circuit and molecular mechanisms
of AD pathogenesis in humans. This will support my efforts to establish a clinical research program evaluating i)
the contribution of sleep disturbance to the onset and progression of various forms of neurodegenerative disease
across clinical stages, ii) the utility of sleep-based biomarkers to predict dementia onset and aid differential
diagnosis between dementias, and iii) the utility of targeted sleep-based interventions to arrest cognitive decline
associated with AD and related dementias. This research proposal and my long-term career goals are supported
by my training plan overseen by my mentoring team which includes experts in hdEEG, uhr-MRI, MTL-dependent
memory circuit function, PET methods in the context of aging and AD—including amyloid and tau PET, clinical
aspects of sleep disorders, geriatric psychiatry, and neurodegenerative disease, and clinical trial design and
implementation in the context of sleep disorders and AD. The proposed training plan includes structured
mentoring on each of these topic...

## Key facts

- **NIH application ID:** 10388218
- **Project number:** 5K01AG068353-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** BRYCE A. MANDER
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $127,254
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388218

## Citation

> US National Institutes of Health, RePORTER application 10388218, Relationships between local and global mechanisms of sleep apnea, Alzheimer's disease biomarkers, and memory impairment in cognitively asymptomatic older adults (5K01AG068353-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10388218. Licensed CC0.

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