Does major surgery impact the development of Alzheimer’s Disease?

by Adrienne Mueller, PhD
December 1, 2021

After major surgery, patients often exhibit cognitive problems that resemble symptoms of Alzheimer’s Disease. This has caused speculation whether undergoing major surgeries could initiate the development or accelerate the progression of chronic neurocognitive disorders. While detection of clinically latent Alzheimer’s Disease (AD) has traditionally been challenging, recent research indicates that plasma levels of tau protein phosphorylated at residue 181 (pTau181) are highly predictive for developing AD in the future. Therefore, if major surgery triggers the increase of pTau181, significant concerns arise regarding its potential contribution to neurodegenerative disorders including AD.

Undergoing major surgery significantly increases Alzheimer’s Disease-associated pTau181 levels.

A team of Stanford scientists led by first author Igor Feinstein, MD, PhD (Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Perioperative and Pain Medicine) and co-senior authors Michael Greicius, MD, MPH (Department of Neurology and Neurological Sciences) and Martin Angst, MD (Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Perioperative and Pain Medicine) investigated the relationship

between major surgery, and plasma pTau181 and neurofilament light (NfL), a marker of neuronal death. Their pilot study, recently reported in JAMA Neurology, measured pTau181 and NfL in patients undergoing either cardiac surgery requiring cardiopulmonary bypass or hip replacement surgery before, during, and after surgery. For both types of surgeries, all patients exhibited low pre-surgical levels of pTau181, below the threshold associated with the progression to AD. However, pTau181 levels significantly increased over 5-fold in cardiac surgery, and about 2.5-fold in hip surgery. Furthermore, pTau181 spikes were followed by a significant increase of NfL on postoperative days 1 and 2 after cardiac surgery only.

Presence of pTau181 is associated with the aggregation of neurofibrillary tangles, a key component of the pathogenesis of AD. Though the role of neurofibrillary tangles in the disorder is still poorly understood, this study provides evidence that major surgery may contribute to neurodegenerative brain pathology echoing AD. Feinstein et al. stress that larger-scale studies tracking more patients over a longer period of time are critical to link observed biochemical changes to cognitive outcomes and the risk of impacting the development of AD.

Additional Stanford Cardiovascular-Institute-affiliated authors who contributed to this study include Edward N. Wilson, Michelle S. Swarovski, and Katrin I. Andreasson.

Dr. Igor Feinstein

Dr. Martin Angst

Dr. Michael Greicius