Circulating Phosphorylated Tau Proteins Linked to Postoperative Delirium

A recent study found that two Alzheimer’s disease biomarkers that circulate in the blood may be used to predict the incidence and severity of postoperative delirium.

Delirium is an acute change in cognition and attention, which may include alterations in consciousness and disorganized thinking. While delirium may affect any age group, it is most common in older patients, especially those with preexisting cognitive impairment. Patients with delirium after surgery recover more slowly than those without delirium and, as a result, have increased length of stay and hospital costs. The measured incidence of postoperative delirium varies with the type of surgery, the urgency of surgery, and the type and sensitivity of the delirium assessment. While generally considered a short-term condition, delirium can persist for months and is associated with poor cognitive and functional outcomes beyond the immediate postoperative period.

Image: Phosphorylation (yellow) of tau proteins (red-orange) by kinases (violet) leads to the formation of Alzheimer’s disease biomarkers that are also associated with postoperative delirium (Photo courtesy of 123rf.com)

Previous clinical studies have demonstrated a strong association between Alzheimer’s disease and delirium. On this basis, investigators at Harvard University’s Massachusetts General Hospital (Boston, USA) and colleagues at the biotechnology company NanoMosaic (Woburn, MA, USA) sought to determine whether Alzheimer’s disease biomarkers in the blood were associated with postoperative delirium.

For this study, the investigators used NonoMosaic’s nanoneedle technology to measure preoperative levels of the phosphorylated tau proteins Tau-PT217 and Tau-PT181 in plasma samples obtained from 139 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy. Presence and severity of postoperative delirium were assessed in the patients.

Results revealed that of the 139 participants, 18 (13%) developed postoperative delirium. The patients who developed postoperative delirium were found to have higher preoperative plasma concentrations of Tau-PT217 and Tau-PT181 than those who did not. Preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were independently associated with postoperative delirium after adjusting for age, education, and preoperative mental state. Overall, Tau-PT217 was a stronger indicator of postoperative delirium than was Tau-PT181.

“These outcomes help diagnosis of postoperative delirium; identify intermediate outcomes that could facilitate clinical studies; and elucidate the insight into potential mechanisms of postoperative delirium, ultimately leading to better and safer postoperative outcomes in patients,” said senior author Dr. Zhongcong Xie, professor of anesthesia at Harvard Medical School. “These data also suggest that tau phosphorylation, contributes, at least partly, to the development of postoperative delirium.”

The study was published in the July 6, 2022, online edition of the journal Annals of Surgery.

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