# Preoperative Occult Neurodegeneration and Postoperative Delirium

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $894,502

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Crosby, Gregory J.
ABSTRACT
Delirium is the most common complication of surgery and anesthesia in older patients, afflicting 15-60% of
those having non-cardiac procedures. This is a major clinical problem because nearly 40% of surgical
procedures are performed on older patients and delirium is associated with serious morbidity, including
accelerated decline to dementia. Still, the cause of postoperative delirium is uncertain and its
neuropathogenesis is unknown. Cerebral neurodegenerative pathology characteristic of Alzheimer’s disease
and related disorders is common even in cognitively normal older people, and by the time even mild symptoms
develop is pronounced. We hypothesize that this preexisting burden of occult cerebral neurodegeneration
accounts for enhanced vulnerability to postoperative delirium (Aim 1), augments surgery- and delirium-induced
cerebral injury (Aim 2), and fuels surgery- and delirium-induced inflammation, which aggravates neural injury
and increases neurodegeneration (Aim 3). We will test these hypotheses in a longitudinal prospective
observational study of older surgical patients evaluated preoperatively for cognitive impairment and followed
postoperatively for delirium and longer-term cognitive decline, with neurodegeneration and neural injury
defined by ultrasensitive plasma biomarkers and cerebral MR imaging. This project is innovative because it
addresses the key question of whether surgery and anesthesia produce delirium and persistent cognitive
decline de novo or by unmasking or exacerbating a cerebral precondition and is significant because of the
magnitude of the clinical problems (neurodegenerative disease, delirium), practicality of the approach (blood-
based biomarkers), and potential to improve the outcomes of vulnerable older surgical patients.
OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10367616
- **Project number:** 1R01AG071741-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** GREGORY CROSBY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $894,502
- **Award type:** 1
- **Project period:** 2022-03-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367616

## Citation

> US National Institutes of Health, RePORTER application 10367616, Preoperative Occult Neurodegeneration and Postoperative Delirium (1R01AG071741-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10367616. Licensed CC0.

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