# Excessive Sleepiness in Preclinical Alzheimer's Disease

> **NIH NIH R03** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $155,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's Disease (AD) is one of the most devastating neurological disorders, and is reaching epidemic
proportions in the context of an aging U.S. population. Current treatment strategies have minimal impact and
only slow the progression of the disorder once cognitive deficits are established. Thus, there is a clear need to
identify persons at risk for AD pathology during the preclinical phase of the disorder, so that preventative
strategies can be developed. Multiple emerging lines of research suggest excessive daytime sleepiness is a
key precognitive symptom related to the Alzheimer's continuum. However, daytime somnolence is
experienced by a large proportion of the general population, and is a non-specific symptom that can reflect
myriad changes in brain function. To further advance this area of research, this project will clarify how specific
objective measures of sleepiness are associated with AD biomarkers in the preclinical phase of the disorder.
This study will address two Specific Aims and three related hypotheses targeted towards this vital area of
inquiry. First, it will verify specific objective measures of sleepiness that map to increased β-amyloid in brain
regions susceptible to early deposition in preclinical AD. Specifically, it will build on preliminary findings that
suggest infrared pupillometry, a measure of noradrenergic tone in the locus coeruleus, is reflective of
increased β-amyloid burden in the supramarginal gyrus. Additionally, it will test the hypothesis that a specific
measure of daytime somnolence, the mean reaction time during the slowest 10% of responses on the
psychomotor vigilance task, which has been previously connected to activity in the default mode network, will
be associated with β-amyloid deposition in the precuneus/posterior cingulate cortex, a key constituent of this
network. Finally, this investigation will clarify whether phosphorylated and total tau protein in the cerebrospinal
fluid are associated with findings from infrared pupillometry as hypothesized, given the locus coeruleus is the
earliest site of abnormal tau deposition observed in AD. This research will be conducted in 75 well-
characterized middle to older-aged adults participating in Wisconsin Alzheimer's Disease Research Center
studies, and will leverage previously collected neuroimaging and biospecimen data, combined with prospective
assessment of daytime sleepiness, longitudinal sleep-wake patterns, and sleep-related breathing disorders, to
perform robust and well-controlled analyses. Addressing the Specific Aims of this application will have a
sizeable impact on AD and sleep research, by linking measureable sleepiness phenotypes to associated
pathological processes in the brain in preclinical AD. In so doing, this project will advance this vital area of
inquiry in preclinical AD, that may lead to the development of improved screening and preventative therapeutic
strategies for the disease.

## Key facts

- **NIH application ID:** 9897520
- **Project number:** 5R03AG063274-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** David T Plante
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,000
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897520

## Citation

> US National Institutes of Health, RePORTER application 9897520, Excessive Sleepiness in Preclinical Alzheimer's Disease (5R03AG063274-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897520. Licensed CC0.

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