# Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $784,183

## Abstract

Project Summary/Abstract
Delirium is a syndrome of fluctuating changes in alertness and attention that occurs in up to 40% of older
surgical patients (i.e. age >65. Delirium is associated with an increased risk of developing dementia, a
progressive loss of thinking and memory skills that eventually results in an inability to care for oneself and to
live independently. The most common cause of dementia in older Americans is Alzheimer’s disease (AD)
which is associated with a progressive buildup of abnormal deposits in the brain of two proteins, tau and
amyloid beta. Amyloid beta deposits typically develop in the brain for years if not decades before the start of
memory deficits and other AD symptoms. Patients with these early or “pre-clinical” amyloid beta deposits, even
if they appear mentally normal, are often at increased risk of developing delirium after surgery. Here, we will
examine whether these amyloid beta deposits, or other “pre-clinical” changes in brain structure and activity,
predispose patients to show larger than normal brain activity changes in response to anesthetic drugs given
during surgery. The central idea of this proposal is that an altered (or exaggerated) brain activity responses to
anesthetic drugs is a marker of an unhealthy brain, i.e. a brain with signs of “pre-clinical” AD and which is at
increased risk of postoperative delirium. First we will examine whether patients with evidence of brain amyloid
beta pathology (as measured by spinal fluid amyloid beta levels) have altered brain activity responses to
anesthetic drugs. Second, we will use brain imaging to determine whether changes early AD-like changes in
brain structure and connections are associated with altered brain activity responses to anesthetic drugs. Third,
we will determine whether altered brain activity responses to anesthetic drugs are associated with increased
postoperative delirium occurrence and severity. This work will help us understand mechanisms underlying
postoperative delirium and AD and related dementias, and the links between them. Further, this work will
provide a way for anesthesiologists (and surgeons) to use brain activity recording data already in wide use in
American operating rooms to predict which patients are likely to develop postoperative delirium and/or AD,
which could allow these patients to be selected for interventions to prevent these disorders.

## Key facts

- **NIH application ID:** 10521860
- **Project number:** 1R01AG073598-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Miles Berger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $784,183
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10521860

## Citation

> US National Institutes of Health, RePORTER application 10521860, Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention (1R01AG073598-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10521860. Licensed CC0.

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