# Blood DNA Methylation Biomarkers of Alzheimer’s Disease and Postoperative Neurocognitive Disorder

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $249,590

## Abstract

Abstract
The most common complication to affect older adults after surgery is the development of a perioperative
neurocognitive disorder. Up to 30% of patients over 60 develop postoperative cognitive dysfunction (POCD),
also termed neurocognitive dysfunction (postoperative) (NCD), within 6 weeks after a surgical procedure.
POCD/NCD is characterized by impairment of memory, attention, learning, concentration and/or executive
function on psychometric testing. Patients with POCD/NCD may experience persistent cognitive dysfunction over
7 years after surgery, greater loss of independence, leaving the labor market, higher health care costs, and
increased morbidity and mortality. The etiology and pathogenesis of POCD/NCD are poorly understood. At
present, no biomarkers of susceptibility to POCD/NCD are available for use before surgery, or for guiding
diagnosis and management of POCD/NCD. Mild cognitive impairment and late onset Alzheimer's disease are
risk factors for cognitive decline after surgery suggesting overlapping pathophysiology. Recently, we reported
over 450 differentially methylated positions in DNA from blood samples that distinguish persons with Alzheimer's
disease from cognitively healthy persons matched for age and sex. Patterns of DNA methylation regulate gene
expression by coordinating the influence of environmental factors and genetic coding sequences. Accordingly,
in this application we will test whether blood samples acquired before surgery provide DNA methylation
biomarkers of Alzheimer's disease that distinguish patients who are at risk for POCD/NCD after surgery from
those who are not (Specific Aim 1). As well, we will test blood samples acquired 6 weeks after surgery for
biomarkers of Alzheimer's disease that are differentially methylated from baseline levels before surgery in
patients with and without POCD/NCD (Specific Aim 2). Our technical innovation is the use of the Illumina Infinium
MethylationEPIC BeadChip to classify DNA methylation status at over 850,000 candidate cytosine loci in
longitudinal blood samples from patients with and without POCD/NCD. These data will provide new predictors
of susceptibility to POCD/NCD for the diagnosis, prognosis, and care of patients with POCD/NCD. In turn,
differentially methylated positions at previously unknown loci and pathways will support a more complete
understanding of heritable and acquired mechanisms that underlie POCD/NCD with potential to identify novel
therapeutic targets.

## Key facts

- **NIH application ID:** 10447364
- **Project number:** 1R21AG077633-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Reid Spencer Alisch
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,590
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447364

## Citation

> US National Institutes of Health, RePORTER application 10447364, Blood DNA Methylation Biomarkers of Alzheimer’s Disease and Postoperative Neurocognitive Disorder (1R21AG077633-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10447364. Licensed CC0.

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