Impact of inhalational anesthetics on neurodegeneration in Alzheimer’s disease: current evidence and potential implications

Alzheimer’s disease is the most common form of dementia, primarily affecting the elderly population. It is a progressive neurodegenerative disease with key pathogenesis hallmarks being amyloid-beta plaque accumulation, and neurofibrillary tangles of tau protein. With an increasingly aging population and rising numbers of surgical procedures, growing interest has been directed towards the potential impact of inhalational anesthetics, particularly isoflurane, sevoflurane and desflurane, in contributing to the neurodegenerative process. Evidence supporting anesthetic-related modulation of Alzheimer’s disease pathways is derived predominantly from in vitro and animal models, with comparatively limited and heterogeneous human biomarker and clinical data. This review will explore the various mechanisms by which these volatile anesthetics contribute to the pathogenesis of neurodegeneration in the context of AD. This includes upregulation of beta-secretase 1 resulting in the formation of amyloid-beta oligomers and inhibition of tau dephosphorylation. While certain studies point towards a neuroprotective effect of these anesthetics, the evidence remains inconsistent. Collectively, these findings support perioperative strategies focused on maintenance of normothermia, optimization of oxygenation, and judicious anesthetic exposure as practical measures to mitigate vulnerability in at-risk populations.