Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease

Abstract

Purpose Postoperative cognitive decline in the elderly has emerged as a major health concern. In addition, there is a growing interest in the potential relationship between general anesthetic exposure and the onset and progression of Alzheimer’s disease (AD). The available evidence of a possible association between anesthesia, surgery, and long-term cognitive effects, including AD, deserves consideration. In this review, we summarize the evidence for anesthesia-induced neurotoxicity in the elderly, while highlighting the limitations of existing data, and we put the literature into perspective for the clinician. Principal findings A growing body of evidence suggests that general anesthetics may be neurotoxic to both young and aging brains. Much of the evidence originates from in vitro and in vivo studies with cells, rodents, and nonhuman primates. Despite the animal data suggesting a relationship between anesthesia and neurotoxicity in the elderly, a definitive link remains elusive in humans. Conclusions The possible relation between anesthetic neurotoxicity, postoperative cognitive dysfunction, and AD remains elusive. It remains unclear whether postoperative cognitive decline in the elderly is related more to perioperative stress and related medical co-morbidities.

General anesthetics in children: neurotoxic or neuroprotective?

“…It operates in two types of receptors, the Trk, expressed in normal conditions and that promotes proper homeostasis and synaptogenesis and the p75NTR receptor which has a higher binding specificity to the BDNF precursor (pro-BDNF). [19] Consequently, there is an accumulation of pro-BDNF in the synaptic clefts with higher binding to p75 NTR receptors, which leads to caspase-3 activation, decreased formation of dendrites and apoptosis. The inhibition of BDNF formation by the anesthetics (especially propofol and isoflurane) also acts indirectly in the neural cell cytoskeleton, pro- This article is available at: www.intarchmed.com and www.medbrary.com 6 moting the destabilization of the actin, one of its structural components, and reducing its survival.…”

Guidelines for general anaesthesia in the elderly of the Committee on Quality and Safety in Anaesthesia, Polish Society of Anaesthesiology and Intensive Therapy

“…Patients over the age of 65 are at a particularly high risk of postoperative confusion (delirium) and cognitive disorders (PCD -Postoperative Cognitive Dysfunction) [29,30]. The guidelines presented in this paper set out the general rules of anaesthesia in elderly patients.…”

Mechanisms of cytotoxicity induced by the anesthetic isoflurane: the role of inositol 1,4,5-trisphosphate receptors

“…Although these anesthetics are generally considered to be safe in clinical anesthesia, several studies have shown that these agents can cause cell damage, neurodegeneration or postoperative cognitive decline Wang et al, 2009;Wei and Xie, 2009;Zhu et al, 2010;Bittner et al, 2011;Campbell et al, 2011;Zou et al 2011). The common inhalational anesthetic isoflurane induces cytotoxicity in both a concentration-and time-dependent manner in different types of cultured cells.…”