Long-Term Post-Operative Cognitive Decline in the Elderly: The Effects of Anesthesia Type, Apolipoprotein E Genotype, and Clinical Antecedents

Issue title: Anesthetics and Alzheimer's Disease

Guest editors: Pravat K. Mandalx and Vincenzo Fodaley

Article type: Research Article

Authors: Ancelin, Marie-Laure^a | de Roquefeuil, Guilhem^a | Scali, Jacqueline^a | Bonnel, François^b | Adam, Jean-François^c | Cheminal, Jean-Claude^b | Cristol, Jean-Paul^d | Dupuy, Anne-Marie^{a; d} | Carrière, Isabelle^a | Ritchie, Karen^{a; *}

Affiliations: [a] Inserm, Montpellier, France; Univ Montpellier 1, Montpellier 1, Montpellier, France | [b] CHU Montpellier, Service d'Orthopédie 3, Hopital Lapeyronie, Montpellier, France | [c] CHU Montpellier, Service Anesthésie, os et articulations, Hopital Lapeyronie, Montpellier, France | [d] CHU Montpellier, Laboratoire de Biochimie, Hopital Lapeyronie, Montpellier, France | [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: Karen Ritchie, Inserm U888, Hopital La Colombiere, 39, avenue C. Flahault, BP 34493, 34093 Montpellier Cedex 5, France. Tel.: +33 4 99 61 45 60; Fax: +33 4 99 61 45 79; E-mail: [email protected].

Abstract: Cognitive dysfunction in the elderly commonly observed following anesthesia has been attributed to age-related neuronal changes exacerbated by pharmacotoxic effects. However, the extent to which these changes may persist following recovery from surgery is still largely unknown. This study investigates the long-term effects of anesthesia on cognitive functioning after orthopedic surgery in 270 elderly patients over the age of 65 who completed a computerized cognitive battery before and 8 days, 4 and 13 months after surgery. Their performance was compared to those of 310 elderly controls who completed the same neuropsychiatric evaluation at baseline and one-year interval. Multivariate analyses adjusted for socio-demographic variables, depressive symptomatology, vascular pathology as well as baseline cognitive performance. We found early and transient post-operative decline in reaction time and constructional praxis. With regard to long-term changes we observed improvement compared to controls in most verbal tasks (probably due to learning effects). On the other hand, a clear dissociation effect was observed for several areas of visuospatial functioning which persisted up to the 13-month follow-up. This specific pattern of visuospatial deficit was found to be independent of apolipoprotein E genotype and closely resembles what has recently been termed vascular mild cognitive impairment, in turn associated with subtle sub-cortical vascular changes. The observation of only minor differences between persons operated by general and regional anesthesia makes it difficult to attribute these changes directly to the anesthetic agents themselves, suggesting that cognitive dysfunction may be attributable at least in part to peri-operative conditions, notably stress and glucocorticoid exposure.

Keywords: Anesthesia, apolipoprotein E, mild cognitive impairment, post-operative cognitive decline

DOI: 10.3233/JAD-2010-100807

Journal: Journal of Alzheimer's Disease, vol. 22, no. s3, pp. S105-S113, 2010