Inhaled General Anesthetics in Alzheimer's Disease Progression: Divergent Effects, Underlying Mechanisms, and Future Perspectives.

Alzheimer's disease (AD) is a devastating, age-related neurodegenerative disorder characterized by progressive cognitive decline, neuronal loss, and hallmark pathologies like β-amyloid (Aβ) deposition and tau hyperphosphorylation. With global aging, more AD patients or high-risk individuals undergo perioperative care, exposing them to inhaled anesthetics such as isoflurane and sevoflurane. Preclinical and clinical evidence on these agents' effects on AD pathogenesis remains conflicting, ranging from exacerbating pathology to neuroprotection, highlighting the critical need to clarify the context-dependent effects and mechanisms driving these outcomes. This review synthesizes how inhaled anesthetics interact with core AD pathologies, highlighting the widely used inhaled anesthetics on AD progression, molecular targets, and exposure parameters. Furthermore, we discuss emerging neuroprotective interventions (e.g., antioxidants, trehalose) that mitigate neuronal damage. These findings inform personalized perioperative strategies for AD-susceptible populations, aiming to reduce iatrogenic risks and improve long-term neurological outcomes.