Anesthesia, surgery, illness and Alzheimer's disease

https://doi.org/10.1016/j.pnpbp.2012.06.011Get rights and content

Abstract

Patients and their families have, for many decades, detected subtle changes in cognition subsequent to surgery, and only recently has this been subjected to scientific scrutiny. Through a combination of retrospective human studies, small prospective biomarker studies, and experiments in animals, it is now clear that durable consequences of both anesthesia and surgery occur, and that these intersect with the normal processes of aging, and the abnormal processes of chronic neurodegeneration. It is highly likely that inflammatory cascades are at the heart of this intersection, and if confirmed, this suggests a therapeutic strategy to mitigate enhanced neuropathology in vulnerable surgical patients.

Highlights

► Major surgery and illness are associated with poor cognitive outcomes in the elderly. ► Anesthesia plays a smaller role than the surgery/illness itself. ► The surgical effect is likely due to peripheral and neuroinflammation. ► Therapy might include reducing inflammatory response to surgery and illness.

Introduction

Sporadic, or late onset, Alzheimer disease, is the most common form of dementia, and is thought to be due to an interaction between specific susceptibility genes and environmental factors. But the environmental factors are poorly understood, exemplified by the recent National Institutes of Health consensus statement that “…firm conclusions cannot be drawn about the association of any modifiable risk factor with cognitive decline or Alzheimer's disease” (Daviglus et al., 2010). Nevertheless, due to the very common complaint of cognitive decline from patients and families following major illness or surgery, there has been recent focus on these environmental factors as enhancing the neuropathology when in the setting of genetic vulnerabilities. The purpose of this brief review is to review the literature to date on surgery and major illness (primarily sepsis) as risk factors for both the timing and prevalence of Alzheimer's dementia.

Section snippets

Human studies

Anecdotes describing post-operative cognitive decline (POCD) have been around for many decades. It was first characterized by Bedford (1955), and then more carefully by Moller, Johnson, Monk and others in the last decade (Johnson et al., 2002, Moller et al., 1998, Monk et al., 2008). Although strict definitions and diagnostic criteria have not been agreed on (Crosby and Culley, 2011, Evered et al., 2011), POCD seems to be a largely time-limited cognitive syndrome in the days to weeks following

Major illness

It has long been assumed that major illness has a deleterious and perhaps prolonged effect on cognition, and perhaps may be a risk factor for dementia. A recent review of the subject concluded that “…neurocognitive sequelae following critical illness are common, may be permanent, and are associated with impairments in daily function” (Hopkins and Jackson, 2006). Two recent human studies have looked more closely at the issue, using similar designs but different patient datasets. Avidan et al.

Neuroinflammation

There have been many proposed mechanisms for the linkage between cognition and the above discussed medical and surgical conditions, but the most obvious, and also most studied, is the inflammatory response, both systemic and focal. The involvement of neuroinflammation in the smoldering pathogenesis of neurodegenerative disorders, now established, was initially suspected because of the salutary effects of chronic non-steroidal anti-inflammatory drug (NSAID) usage, but more recently through

Conclusion

Major illness and surgery have both been associated with an enhancement in the pathogenesis of chronic neurodegenerative diseases, such as Alzheimer's disease, and in some cases, worsening of the cognitive outcome of this pathogenesis. Anesthesia or anesthetics, although implicated mechanistically in both in vitro and animal studies, appear to play a smaller role than surgery, although their potential to modulate the inflammatory response remains understudied. The surgical effect, like that of

Acknowledgments

This work was supported in part by NIH AG031742 and the Austin Lamont Endowment.

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