Iatrogenic Risk Factors for Alzheimer's Disease: Surgery and Anesthesia

Issue title: Anesthetics and Alzheimer's Disease

Guest editors: Pravat K. Mandalx and Vincenzo Fodaley

Article type: Review Article

Authors: Vanderweyde, Tara^a | Bednar, Martin M.^b | Forman, Stuart A.^c | Wolozin, Benjamin^{d; *}

Affiliations: [a] Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA | [b] Neuroscience Research Unit, Pfizer Inc. Groton, CT, USA | [c] Department of Anesthesia Critical Care & Pain Medicine, Massachusetts General Hospital, Boston, MA, USA | [d] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [x] Neurospectroscopy and Neuroimaging Laboratory, National Brain Research Center, Manesar, Gurgaon, India | [y] Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina, Policlinico G. Martino, Messina, Italy

Correspondence: [*] Correspondence to: Benjamin Wolozin, M.D., Ph.D., Professor of Pharmacology and Neurology, Boston University School of Medicine, 72 East Concord St., R-614, Boston, Massachusetts 02118-2526, USA. Tel.: +1 617 414 2652; E-mail: bwolozin@bu.edu.

Abstract: Increasing evidence indicates that patients develop post-operative cognitive decline (POCD) following surgery. POCD is characterized by transient short-term decline in cognitive ability evident in the early post-operative period. This initial decline might be associated with increased risk of a delayed cognitive decline associated with dementia 3 to 5 years post-surgery. In some studies, the conversion rates to dementia are up to 70% in patients who are 65 years or older. The factors responsible for the increased risk of dementia are unclear; however, clinical studies investigating the prevalence of POCD and dementia following surgery do not show an association with the type of anesthesia or duration of surgery. Epidemiological studies from our group support this observation. The adjusted Hazard Ratios for developing dementia (or AD specifically) after prostate or hernia surgery were 0.65 (95% CI, 0.51 to 0.83, prostate) and 0.65 (95% CI, 0.49 to 0.85, hernia) for cohorts of subjects exposed to general anesthesia compared to those exposed only to local anesthesia. Animal studies suggest that prolonged exposure to some volatile-inhalational anesthetics increase production of amyloid-β and vulnerability to neurodegeneration, but these results are weakened by the absence of clinical support. Inflammation and a maladaptive stress response might also contribute to the pathophysiology of this disorder. Future research needs to identify predisposing factors, and then strategies to protect against POCD and subsequent dementia. The field also needs to adopt a more rigorous approach to codifying the frequency and extent of early and delayed post-operative cognitive decline.

Keywords: Alzheimer's disease, amyloid-β protein, anesthetics, coronary artery bypass operation dementia, surgery

DOI: 10.3233/JAD-2010-100843

Journal: Journal of Alzheimer's Disease, vol. 22, no. s3, pp. S91-S104, 2010