Neuroinflammatory challenges compromise neuronal function in the aging brain: Postoperative cognitive delirium and Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that targets memory and cognition, and is the most common form of dementia among the elderly. Although AD itself has been extensively studied, very little is known about early-stage preclinical events and/or mechanisms that may underlie AD pathogenesis. Since the majority of AD cases are sporadic in nature, advancing age remains the greatest known risk factor for AD. However, additional environmental and epigenetic factors are thought to accompany increasing age to play a significant role in the pathogenesis of AD. Postoperative cognitive delirium (POD) is a behavioral syndrome that primarily occurs in elderly patients following a surgical procedure or injury and is characterized by disruptions in cognition. Individuals that experience POD are at an increased risk for developing dementia and AD compared to normal aging individuals. One way in which cognitive function is affected in cases of POD is through activation of the inflammatory cascade following surgery or injury. There is compelling evidence that immune challenges (surgery and/or injury) associated with POD trigger the release of pro-inflammatory cytokines into both the periphery and central nervous system. Thus, it is possible that cognitive impairments following an inflammatory episode may lead to more severe forms of dementia and AD pathogenesis. Here we will discuss the inflammation associated with POD, and highlight the advantages of using POD as a model to study inflammation-evoked cognitive impairment. We will explore the possibility that advancing age and immune challenges may provide mechanistic evidence correlating early life POD with AD. We will review and propose neural mechanisms by which cognitive impairments occur in cases of POD, and discuss how POD may augment the onset of AD.