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

Zhongcong Xie, Celeste A Swain, Sarah A P Ward, Hui Zheng, Yuanlin Dong, Neelakantan Sunder, Dennis W Burke, Diana Escobar, Yiying Zhang, Edward R Marcantonio, Zhongcong Xie, Celeste A Swain, Sarah A P Ward, Hui Zheng, Yuanlin Dong, Neelakantan Sunder, Dennis W Burke, Diana Escobar, Yiying Zhang, Edward R Marcantonio

Abstract

Objective: The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) βamyloid 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% males) 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% versus 17%, P=0. 0482) and greater symptom severity of postoperative delirium (Aβ40/Tau ratio: 4 versus 3, P=0. 034; Aβ42/Tau ratio: 4 versus 3, P=0. 062, the median of the highest Memorial Delirium Assessment Scale 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 Memorial Delirium Assessment Scale 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.

Keywords: Aβ/Tau ratio; Cerebrospinal fluid; delirium; surgery.

Figures

Figure 1
Figure 1
Flow diagram. The flow diagram shows that 354 participants were initially screened for the studies and finally 153 participants were included in the data analysis.
Figure 2
Figure 2
The postoperative delirium incidence in the first quartile and the combination of the other three quartiles of CSF Aβ40/Tau or Aβ42/Tau ratio. Chi-square test shows that there is a significant difference in the postoperative delirium incidence between the first quartile (red bar) and the combination of the second, third, and fourth quartiles (blue bar) of CSF Aβ40/Tau (A) or Aβ42/Tau ratio (B).
Figure 3
Figure 3
The postoperative delirium severity in the first quartile and the combination of the other three quartiles of CSF Aβ40/Tau or Aβ42/Tau ratio. (A) Mann–Whitney test suggests that there is a significant difference in the highest MDAS score between the first quartile (red bar) and the combination of the second, third, and fourth quartiles (blue bar) of CSF Aβ40/Tau. (B) Mann–Whitney test suggests that there is a borderline difference in the highest MDAS score between the first quartile (red bar) and the combination of the second, third, and fourth quartiles (blue bar) of CSF Aβ42/Tau ratio.

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