Abstract
Background: Postoperative cognitive dysfunction (POCD) following anesthesia and surgery is a common and severe complication, especially in elderly patients. A pre-existing cognitive impairment may impart susceptibility to further cognitive dysfunction; the mechanism remains unclear. We hypothesized that the specific impacts of anesthesia and surgery on individuals with preclinical Alzheimer’s disease (AD) may render them more susceptible to an increase in the risk of cognitive impairment. The aim of this study was to compare the cognitive impairment between normal adult mice and those with preclinical AD after propofol anesthesia and surgery.Methods: We performed abdominal surgery in cognitively pre-symptomatic, 5-month-old male mice with sporadic AD (apolipoprotein E4 allele, ApoE4-KI) and age-matched (C57BL/6J) controls. Propofol anesthesia (170 mg/kg) was induced via retro-orbital injection over 2 h. Morris water maze (MWM) and Y-maze tests were conducted 2 days before and 2, 4, and 7 days after surgery. The mean escape latencies and spontaneous alternation percentages were the major outcomes. Neuronal apoptosis in hippocampal sections was evaluated using the terminal dUTP nick-end labeling (TUNEL) assay. Hippocampal amyloid beta (Aβ) levels were assessed via quantitative immunohistochemistry (IHC).Results: The control mice exhibited increased mean escape latencies of MWM at postoperative 2 and 4, but not at day 7; ApoE4-KI mice exhibited such increases at postoperative days 2, 4 and 7. Significant differences between ApoE4-KI and control mice in terms of the mean escape latencies were evident at days 2 and 7 (both P < 0.05). However, performance on a non-hippocampal memory tasks (Y-maze test) did not differ. More TUNEL-positive neurons were evident in the hippocampal CA3 region of ApoE4-KI mice at postoperative days 2 and 4, but not at day 7 compared to the control group (both P < 0.05). IHC revealed significantly elevated Aβ deposition in the hippocampal CA3 region of ApoE4-KI mice at postoperative days 4 and 7 compared to control mice (both P < 0.05).Conclusions: Propofol anesthesia followed by surgery induced persistent changes in cognition, and pathological hippocampal changes in pre-symptomatic, but vulnerable AD mice. It would be appropriate to explore whether preclinical AD patients are more vulnerable to POCD development.
Highlights
Post-operative cognitive dysfunction (POCD) after anesthesia and surgery is a common severe complication, especially in elderly patients
Two-way analysis of variance (ANOVA) revealed a significant effect of time. ‡P < 0.01, †P < 0.05, two-way ANOVA and the Tukey HSD post hoc test
We found that hippocampal cognitive function was more impaired in mice with preclinical Alzheimer’s disease (AD) than in control mice after propofol anesthesia and surgery
Summary
Post-operative cognitive dysfunction (POCD) after anesthesia and surgery is a common severe complication, especially in elderly patients. POCD is characterized by a loss of attention, memory impairment, and personality changes that persist for months or years (Qiao et al, 2015). The 1-week and 3-month incidences of POCD in surgical patients aged over 60 years are 25.8–41.4% and 9.9–12.7% respectively (Moller et al, 1998; Monk et al, 2008). POCD has been associated with various adverse outcomes, including impaired recovery and increased morbidity and mortality (Saczynski et al, 2012). Postoperative cognitive dysfunction (POCD) following anesthesia and surgery is a common and severe complication, especially in elderly patients. We hypothesized that the specific impacts of anesthesia and surgery on individuals with preclinical Alzheimer’s disease (AD) may render them more susceptible to an increase in the risk of cognitive impairment. The aim of this study was to compare the cognitive impairment between normal adult mice and those with preclinical AD after propofol anesthesia and surgery
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