Preoperative sedentary behavior is neither a risk factor for perioperative neurocognitive disorders nor associated with an increase in peripheral inflammation, a prospective observational cohort study

Abstract

Background Surgical interventions result in a postoperative rise in circulating inflammatory cytokines and high molecular group box protein 1 (HMGB1). Herein, the impact of a sedentary lifestyle and other age-related factors on the development of perioperative neurocognitive disorders (PND) following non-cardiac surgical procedures was assessed in an older (55–75 years-old) surgical population. Methods Prior to surgery, patients were asked questions regarding their sedentary behavior and daily habits. They also passed the Mini Mental State Examination (MMSE) and their blood circulating interleukin 6 (IL-6) and HMGB1 levels were assayed by ELISA. IL-6 and HMGB1 measurements were repeated respectively 6 and 24 h after surgery. MMSE was re-evaluated 6 weeks and whenever possible 3 months after surgery. Results Thirty-eight patients were enrolled in the study from January until July 2019. The study identified self-sufficiency, multilinguism, and overall health score on the geriatric depression scale, as protectors against PND. No other demographic (age, sex), environmental (solitary/non-solitary housing, professional and physical activities, smoking, alcohol drinking), comorbidity (antipsychotic drug uptake, diabetic state) and type of surgery (orthopedic, general, genitourinary) influenced the development of PND. Although some factors (surgery type and age) influenced the surgery-induced rise in the circulating IL-6 levels, they did not impact HMGB1. Conclusion Inflammaging, reflected by the greater increment of surgery-induced IL-6 in patients with advanced age, was present. As trauma-induced release of HMGB1 was not similarly affected by age, we surmise that HMGB1, rather than circulating cytokines, is the key driver of the trauma-induced inflammatory cascade leading to PND. Trial registration Clinicaltrials.gov identifier: NCT03805685.

Isoflurane impairs GluN2B‐containing NMDA receptors trafficking and cognition via decreasing histone acetylation and EphB2 expression in aged hippocampal neurons

“…1,63 In fact, most clinical studies have shown that gender does not influence the development of PND. [64][65][66][67] In addition, basic studies did not consider the factor of gender, and male rats or mice were used. 68,69 In the present study, we used male mice to focus on the factor of age.…”

“…PND is a complicated entity with subjective variability and numerous contributory factors, which are grouped into patient‐, surgical‐ and anaesthesia‐related factors, and for patient factors including age, educational level, mental health and comorbidities 1,63 . In fact, most clinical studies have shown that gender does not influence the development of PND 64–67 . In addition, basic studies did not consider the factor of gender, and male rats or mice were used 68,69 .…”

Early postoperative risk prediction of neurocognitive decline

“…In a previous pilot study on the effects of sedentary behaviour on development of PNDs in 38 surgical patients, mini-mental state examination (MMSE) scores (range 0e30) decreased from (mean [standard deviation]) 25.8 (4.2) at baseline to 23.6 (4.8) at 6 weeks after surgery (P<0.01). 6 An increase in pro-inflammatory markers was concomitantly observed during the first postoperative day; IL-6 levels increased from 31.2 (33.9) at baseline to 290 (277) pg ml À1 after 24 h, and HMGB1 levels increased from 38.9 (85.6) to 91.1 (170) pg ml À1 (P<0.0001). 6 A crucial question raised by this clinical study that evaluated both cognitive and biological assessments of surgical patients is whether or not development of PND, as reflected by a decline in the MMSE, can be predicted at an early juncture.…”

“…6 An increase in pro-inflammatory markers was concomitantly observed during the first postoperative day; IL-6 levels increased from 31.2 (33.9) at baseline to 290 (277) pg ml À1 after 24 h, and HMGB1 levels increased from 38.9 (85.6) to 91.1 (170) pg ml À1 (P<0.0001). 6 A crucial question raised by this clinical study that evaluated both cognitive and biological assessments of surgical patients is whether or not development of PND, as reflected by a decline in the MMSE, can be predicted at an early juncture.…”

Defining the role of Interleukin-6 for the development of perioperative neurocognitive disorders: Evidence from clinical and preclinical studies

“…Key inflammatory processes that were noted in animal models are also present in surgical patients. Shortly after surgical incision, circulating HMGB1 levels begin to rise ( Saxena et al, 2020 ) followed by an increase in pro-inflammatory cytokines ( Hirsch et al, 2016 ; Lammers-Lietz et al, 2022 ), disruption of the BBB ( Danielson et al, 2018 ), infiltration of monocytes into the brain ( Berger et al, 2019 ) and activation of microglia ( Forsberg et al, 2017 ).…”