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Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania

Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania roderic.eckenhoff@uphs.upenn.edu. Disclosure: No conflicts. Background: Durable post-operative cognitive decline in older people. Positive odds ratio for Alzheimer disease and prior surgery.

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Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania

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  1. Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania roderic.eckenhoff@uphs.upenn.edu Disclosure: No conflicts • Background: • Durable post-operative cognitive decline in older people. • Positive odds ratio for Alzheimer disease and prior surgery. • Biophysical basis for enhanced protein oligomerization. Hypothesis:Inhaled anesthetics promote aggregation and toxicity of disease-associated peptides, and thereby accelerate the onset of neurodegenerative disorders, like Alzheimers. • Methods: • In vitro protein studies – Aβ.1-40 and Aβ1-42 . • Cell culture models – exogenous and endogenous. • Transgenic animal models of enhanced Aβ expression.

  2. Isolated proteins Anesthesiology 2004;101:703 Current Alzheimer Research 2007 (in press)

  3. † # * * LDH release, % change from control * * † # * Cell Culture Anesthesiology 2004;101:703

  4. WT Tg C H I C H I Animals: Tg2576

  5. Impact of Prior Anesthesia History on ADSilber & Rosenbaum analysis of Bohnen papers P=0.11 one sided P=0.08 one sided

  6. Conclusions: • Inhaled anesthetics accelerate aggregation of Aβ. Halo>Iso • Inhaled anesthetics stabilize the toxic Aβ oligomer. • Aβ plus anesthetic is more cytotoxic than either alone. • Inhaled anesthetics enhance plaque in transgenic mouse brain. • Isoflurane causes learning/memory impairment in old WT mice. • Future directions: • Rank-order effects for all these actions. • Effects at pre-symptomatic stage. • Large epidemiologic studies. • Biomarker studies.

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