Anesthesia and the risk of dementia in the elderly (2023)

La Presse Médicale, Volume 47, Issue 4, Part 2, 2018, pp. e73-e81

The brain is both the orchestrator as well as the target of the innate immune system's response to the aseptic trauma of surgery. When trauma-induced inflammation is not appropriately regulated persistent neuro-inflammation interferes with the synaptic plasticity that underlies the learning and memory aspects of cognition. The complications that ensue, include postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) at two poles of a constellation that is now termed perioperative neurocognitive disorders. While the relationship of acute POD to the more indolent POCD is not completely understood both can be further complicated by earlier-onset of dementia and higher mortality. How and why these disorders occur is the focus of this report. The innate immune system response to peripheral trauma signals to the brain through a regulated cascade of cellular and molecular actors producing a teleological defense mechanism, “sickness behavior,” to curtail further injury and initiate repair. Sickness behavior, including disordered cognition, is terminated by neural and humoral pathways that restore homeostasis and launch the organism on a path to good health. With so many “moving parts” the innate immune system is vulnerable in clinical settings that include advanced age and lifestyle-induced diseases such as “unhealthy” obesity and the inevitable insulin resistance. Under these conditions, inflammation may become exaggerated and long-lived. Consideration is provided how to identify the high-risk surgical patient and both pharmacological (including biological compounds) and non-pharmacological strategies to customize care.

Journal of Clinical Anesthesia, Volume 67, 2020, Article 110038

La Presse Médicale, Volume 47, Issue 4, Part 2, 2018, pp. e65-e72

Cognition is essential to all aspects of our everyday life. Although we take our cognitive function for granted, the perioperative period is prone to several aggressions that might impair it. Postoperative cognitive dysfunction, has been the aim of many studies recently, and was shown to be very common with an incidence that can reach 40%, yielding not only impairment in cognition, but also longer hospital stays, higher costs and greater mortality. While several studies have revealed some of the mechanisms contributing to postoperative cognitive dysfunction, the search for the perfect instrument to screen and measure cognitive (dys)function has proven more elusive. The present paper aims to review several cognitive evaluation methods, discussing their advantages and disadvantages as well as their potential clinical applications in evaluating the dynamics of the recovery of cognitive function after anesthesia and surgery. The current availability of easy to use computerized tests might provide the tools necessary to identify patients at risk, and promptly provide them with the adequate course of action.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 47, 2013, pp. 128-134

In view of multiple prospective investigations reporting an incidence of 10% or greater in elderly patients after cardiac and non-cardiac procedures, it is surprising that no families, twins or even individual cases have been reported with persistent post-operative cognitive dysfunction (POCD) or post-operative dementia (POD) that is otherwise unexplained. As POCD and POD research has shifted in recent years from surgical and anesthetic variables to predictors of intrinsic, patient-specific susceptibility, a number of markers based on DNA sequence variation have been investigated. Nevertheless, no heritable, genomic indices of persistent POCD or post-operative dementia lasting 3months or longer after surgery have been identified to date. The present manuscript surveys challenges confronting the search for markers of heritable vulnerability to POCD and POD, and proposes steps forward to be taken now, including the addition of surgical and anesthetic descriptors to ongoing longitudinal dementia protocols and randomized clinical trials (RCTs) comprising serial psychometric testing, and a fresh focus on phenotypes and genotypes shared between outliers with “extreme” POCD and POD traits.

La Presse Médicale, Volume 47, Issue 4, Part 2, 2018, pp. e43-e44

European Journal of Pharmacology, Volume 741, 2014, pp. 150-155

To investigate the effects of dobutamine hydrochloride on early postoperative cognitive dysfunction (POCD) and plasma tumor necrosis factor (TNF)-α concentration in patients undergoing hip arthroplasty, 124 patients undergoing unilateral total hip arthroplasty, aged 70–92 years old, were randomly assigned to four groups (n=31) as follows: a control group of patients receiving only saline (intravenous infusion, i.v.); and groups receiving 2, 4, or 6μgkg⁻¹min⁻¹ (i.v.) of dobutamine hydrochloride. Cognitive functions were assessed on the day before surgery (T1), and the 1st day (T2), 3rd day (T3), and 7th day (T4) postsurgery using the Mini Mental State Examination (MMSE). The plasma TNF-α protein level was determined 10min before anesthesia (Ta), and 10min (Tb), 30min (Tc), and 60min (Td) after anesthesia by an enzyme-linked immunosorbent assay. Cognitive disorder was observed within the first 3 days after hip arthroplastic surgery, and it had recovered 7 days after the operation in the control group of patients. Administration of 2 or 4μgkg⁻¹min⁻¹ dobutamine hydrochloride was able to reverse the early POCD. Simultaneously, an increase of plasma TNF-α levels 30min after anesthesia was observed (41.34±9.61 vs. 27.75±5.45), which was significantly suppressed by the administration of low-dose dobutamine hydrochloride (29.23±7.32 vs. 41.34±9.61) but not by high-dose dobutamine hydrochloride (45.9±12.11 vs. 41.34±9.61). Together, our data indicated that the plasma concentration of TNFα was engaged in the effect of dobutamine hydrochloride on POCD.