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

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.

Tau Phosphorylation and Sevoflurane Anesthesia

“…Several clinical studies failed to provide a link between anesthesia and POCD, obviously because of the difficulty to distinguish between the respective involvement of either anesthesia itself, surgery, perioperative conditions, inflammation, pain, and comorbidities. 8,12,58 For instance, it is clear that sevoflurane increases tau and P-tau levels in the cerebrospinal fluid of surgical patients for at least 48 h and that some surgery, such as coronary artery bypass, also allows for increase in phosphotau, as detected in cerebrospinal fluid. 59,60 Thus, animal studies provide a tool to circumscribe instrumental factors and adapt these findings to clinical practice, at least in the choice of which anesthetic agents to be used.…”

“…2C). Noteworthy was that to avoid any confounding effects related to hypothermia, 12 animal temperature was maintained close to 37°C (37.3°Ϯ 1°C) throughout experiments. Since oxidant injury (e.g., inflammation) can reproduce some changes reported in this first experiment, some control mice were also exposed to 100% oxygen, as done in sevoflurane conditions.…”

“…9,10 Thus, while etiology of POCD remains unclear so far, anesthetic agents might be involved. 11,12 Although halogenated agents are thought to have limited effects on POCD, 13,14 sevoflurane anesthesia has been shown to alter exploratory and anxiety-like behavior in animals with a genetically modified cholinergic system. 15 Interestingly, we recently showed cholinergic deficits in a tau transgenic model 16,17 and recent experimental in vivo studies showed that exposure to different anesthetic agents induces rapid, massive, and transient hyperphosphorylation of tau.…”

Management of cognition as reported in Japanese historical documents and modern anesthesiology research papers

“…With advances in surgical technologies, invasive surgeries are more often performed on a progressively older and sicker population, who are at particular risk for cerebral injury during surgery [17]. Apart from aging or acquired diseases, congenital genetic variations, such as apolipoprotein genotype, have also been reported to affect susceptibility to injury as well as the ability to recover following injury [18,19].…”

Anesthesia, Surgery and Neuroinflammation

“…For example, children having more than 3 surgeries before the age of 3 may be at risk of both behavioral and intellectual compromise later in life (3,4). Furthermore, in the elderly, anesthesia and surgery have been suggested to contribute to the development of delirium and Alzheimer disease (AD), and yet, if true, it is unclear whether anesthesia, or surgical stress itself is the trigger (5,6). But to put this into perspective, the occurrence of POCDS at the extremes of age may be related to particular vulnerabilities associated with development and/or aging.…”