# Biological signatures of neurodegeneration and aging associated with delirium in older adults following hip fracture surgery

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $161,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Delirium is a life-threatening acute disturbance in mental status affecting more than 2.6 million hospitalized
adults in the United States annually. Delirium is associated with many poor clinical outcomes, including decline
in physical function, new or accelerated cognitive impairment, and death. Delirium is significantly more
common in older adults, and those with mild cognitive impairment (MCI), Alzheimer's Disease, or Alzheimer's
Disease Related Dementias (AD/ADRD). While delirium prevention efforts are critically important, they fail to
prevent approximately 60% of cases. Insufficient knowledge of the underlying pathophysiology of delirium
dramatically hinders advances in personalized delirium risk assessment, prevention, and impedes the
development of delirium treatments, which do not currently exist. The complex association between delirium,
cognitive impairment, and advanced age is largely established by epidemiologic studies rather than the
identification of biological markers. There is growing evidence for plasma biomarkers, such as tau
phosphorylated at two sites (pTau181, pTau217) and neurofilament light chain (NfL), to distinguish healthy
controls from those with AD, which is an important innovation from cerebrospinal fluid testing. While advanced
age is a major risk factor for both delirium and AD/ADRD, this is based on chronological age – the number of
years alive. However, aging is increasingly understood to be driven by biological mechanisms that are more or
less advanced in different individuals. This biological age can be distinguished from chronological age, and the
difference between biological and chronologic age is “age acceleration,” which is associated with increased
risk of chronic disease, including AD. One specific mechanism of biological aging is the accumulation of
senescent cells in a state of cell cycle arrest that is associated with increased risk of chronic disease. This
proposal is the first application of plasma pTau181, pTau217 and signatures of biological aging (age
acceleration, cellular senescence) in delirious patients. The goal of this project is to identify whether elevated
preoperative measures of pTau181, pTau217, NfL, and age acceleration in blood, and intraoperative measures
of senescent cell burden in tissue, are associated with postoperative delirium in 100 older adults undergoing
hip fracture surgery in order to advance our understanding of the pathologic drivers of delirium. We will also
quantify whether these biomarkers are affected by external stressors (e.g., hip fracture surgery with
anesthesia). This project will shed light on the pathological basis for the observed association between
delirium, neurodegeneration and aging, and lay the foundation for my development as an early-stage clinician-
investigator at the intersection of neurology and geriatrics. Findings from this study will provide the basis for a
future career development award application to investigate ho...

## Key facts

- **NIH application ID:** 10302138
- **Project number:** 1R03AG074035-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Sara Catherine LaHue
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,500
- **Award type:** 1
- **Project period:** 2021-07-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302138

## Citation

> US National Institutes of Health, RePORTER application 10302138, Biological signatures of neurodegeneration and aging associated with delirium in older adults following hip fracture surgery (1R03AG074035-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10302138. Licensed CC0.

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