Preoperative cerebrospinal fluid β-Amyloid/Tau ratio and postoperative delirium

Authors

  • Zhongcong Xie,

    Corresponding author
    1. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
    • Correspondence

      Zhongcong Xie, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129. Tel: 617-724-9308; Fax: 617-643-9277; E-mail: zxie@mgh.harvard.edu

    Search for more papers by this author
  • Celeste A. Swain,

    1. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
    Search for more papers by this author
  • Sarah A. P. Ward,

    1. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
    Search for more papers by this author
  • Hui Zheng,

    1. MGH Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
  • Yuanlin Dong,

    1. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
    Search for more papers by this author
  • Neelakantan Sunder,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
  • Dennis W. Burke,

    1. Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
  • Diana Escobar,

    1. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
    Search for more papers by this author
  • Yiying Zhang,

    1. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
    Search for more papers by this author
  • Edward R. Marcantonio

    1. Divisions of General Medicine and Primary Care and Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author

Abstract

Objective

The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) β-amyloid protein (Aβ) and high CSF Tau levels are associated with Alzheimer's disease. We, therefore, assessed whether lower preoperative CSF Aβ/Tau ratio was associated with higher incidence and greater severity of postoperative delirium.

Methods

One hundred and fifty-three participants (71 ± 5 years, 53% men) who had total hip/knee replacement under spinal anesthesia were enrolled. CSF was obtained during initiation of spinal anesthesia. The incidence and severity of postoperative delirium were determined by Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS) on postoperative day 1 and 2. Aβ40, Aβ42, and Tau levels in the CSF were measured by enzyme-linked immunosorbent assay. The relationships among these variables were determined, adjusting for age and gender.

Results

Participants in the lowest quartile of preoperative CSF Aβ40/Tau and Aβ42/Tau ratio had higher incidence (32% vs. 17%, P = 0.0482) and greater symptom severity of postoperative delirium (Aβ40/Tau ratio: 4 vs. 3, P = 0.034; Aβ42/Tau ratio: 4 vs. 3, P = 0.062, the median of the highest MDAS score) as compared to the combination of the rest of the quartiles. The preoperative CSF Aβ40/Tau or Aβ42/Tau ratio was inversely associated with MDAS score (Aβ40/Tau ratio: −0.12 ± 0.05, P = 0.014, adj. −0.12 ± 0.05, P = 0.018; Aβ42/Tau ratio: −0.65 ± 0.26, P = 0.013, adj. −0.62 ± 0.27, P = 0.022).

Interpretation

Lower CSF Aβ/Tau ratio could be associated with postoperative delirium, pending confirmation of our preliminary results in further studies. These findings suggest potential roles of Aβ and/or Tau in postoperative delirium neuropathogenesis.

Ancillary