# Sleep Impairment: A Mechanism Explaining Neuropsychiatric Symptoms in Alzheimer's

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $835,917

## Abstract

Project Summary/Abstract: Alzheimer’s disease (AD) and its related neuropathology are linked to a set of
neuropsychiatric symptoms (NPS) that come with marked clinical, personal and real-life burden. However,
the underlying neural mechanisms of NPS are poorly defined, hindering novel treatment approaches. Core
among these NPS are: 1) sleep disturbance, and 2) anxiety. Moreover, both sleep impairment and anxiety
are independently associated with a faster rate of longitudinal cognitive decline, reinforcing a particular
focus on their overlap. However, the possibility that AD pathology, impaired non-rapid eye movement
(NREM) sleep and the NPS feature of anxiety are actually inter-related, representing a novel brain
mechanism explaining why Aβ is associated with increased anxiety, has not been examined. Here, we seek
to test a core mechanistic hypothesis: The impact of Aβ burden on anxiety is orchestrated through beta-
amyloid (Aβ)-related impairment of NREM slow-wave sleep, which in turn, amplifies next-day anxiety
through impaired mPFC-amygdala emotional brain regulation. If supportive, these studies would (i)
advance our basic understanding of how AD-related pathology mechanistically impacts the NPS feature of
anxiety through impairment of NREM sleep, and (ii) establish sleep improvement as a novel modifiable
therapeutic intervention target that may de-escalate anxiety linked with the AD disease state, and potentially
the rate of longitudinal disease/cognitive decline.

## Key facts

- **NIH application ID:** 10272379
- **Project number:** 1R01MH126901-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Matthew P Walker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $835,917
- **Award type:** 1
- **Project period:** 2021-06-18 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10272379

## Citation

> US National Institutes of Health, RePORTER application 10272379, Sleep Impairment: A Mechanism Explaining Neuropsychiatric Symptoms in Alzheimer's (1R01MH126901-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10272379. Licensed CC0.

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