Consensus Statement: First International Workshop on Anesthetics and Alzheimer’s Disease

Баранов, Д А; Bickler, Philip E.; Crosby, Gregory; Culley, Deborah J.; Eckenhoff, Maryellen F.; Eckenhoff, Roderic G.; Hogan, Kirk; Jevtović-Todorović, Vesna; Palotás, András; Perouansky, Misha; Planel, Emmanuel; Silverstein, Jeffrey H.; Wei, Huafeng; Whittington, Robert A.; Xie, Zhongcong; Zuo, Zhiyi

doi:10.1213/ane.0b013e318199dc72

Cited by 116 publications

(72 citation statements)

References 33 publications

(34 reference statements)

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“…Few attempts have been made to relate POCD or PreCI to the onset of dementia in the longer term. This is unfortunate because recent animal studies suggest an association between cognitive change after anesthesia and the pathophysiology of AD 10,34 ; however, this link has not been shown in clinical studies. The wealth of data outlining the progression of aMCI to dementia in population studies cannot be applied to PreCI because of the discrepancy in definitions between the two constructs.…”

Section: Discussionmentioning

confidence: 99%

Preexisting Cognitive Impairment and Mild Cognitive Impairment in Subjects Presenting for Total Hip Joint Replacement

et al. 2011

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Background The prevalence of preexisting cognitive impairment (PreCI) is documented before cardiac surgery, but there is less information before noncardiac surgery. In addition, the prevalence of mild cognitive impairment, defined by different cognitive criteria and subjective complaints, and which may progress to Alzheimer disease, is unknown in these subjects. Because anesthesia and surgery have been implicated in Alzheimer disease pathology, we prospectively measured PreCI and mild cognitive impairment in subjects scheduled for total hip joint replacement surgery in an observational study. Methods One hundred fifty-two subjects 60 y of age and older who were scheduled for total hip joint replacement surgery underwent assessment, including neuropsychologic testing, 1 week before surgery. Test results were compared with published norms. PreCI was defined as impairment in two or more of seven cognitive tests, for which impairment in an individual test was defined as ≥ 2 SD below norms for that test. Amnestic mild cognitive impairment (aMCI) was defined as impairment ≥1.5 SD below norms for results of the immediate and/or delayed Auditory Verbal Learning Test plus a subjective complaint. Results Subjects performed worse compared with normative data on five of seven neuropsychologic tests. Thirty (20% [95% CI, 13-26%]) subjects were classified as having PreCI. Thirty-four (22% [95% CI, 16-29%]) were classified as having aMCI. Ten (7%) subjects were classified as having both PreCI and aMCI, representing 33% of the 30 subjects with PreCI. Conclusions The prevalence of aMCI in subjects scheduled for total hip joint replacement surgery is similar to that in the general community. PreCI and aMCI tend to identify different subjects. Because aMCI is known to progress to Alzheimer disease, future studies that track cognition before and after anesthesia and surgery should document the presence or absence of aMCI so that the rate of conversion to Alzheimer disease after anesthesia and surgery can be compared with the rate in the nonsurgical population.

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Section: Discussionmentioning

confidence: 99%

Preexisting Cognitive Impairment and Mild Cognitive Impairment in Subjects Presenting for Total Hip Joint Replacement

et al. 2011

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“…The consensus statement of the First International Workshop on Anesthetics and Alzheimer's Disease 22 concluded that ‘there is sufficient evidence at multiple levels to warrant further and more definitive investigations of the onset and progression of Alzheimer's disease and neurodegeneration after anesthesia and surgery’. We therefore undertook a longitudinal cohort study of cognitive function in patients and controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA), who were followed with frequent cognitive assessments and records of episodes of anaesthesia for surgery.…”

Section: Introductionmentioning

confidence: 99%

Cognitive decline in the elderly after surgery and anaesthesia: results from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort

et al. 2016

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SummaryConcerns have been raised about the effects on cognition of anaesthesia for surgery, especially in elderly people. We recorded cognitive decline in a cohort of 394 people (198 women) with median (IQR) age at recruitment of 72.6 (66.6–77.8) years, of whom 109 had moderate or major surgery during a median (IQR) follow‐up of 4.1 (2.0–7.6) years. Cognitive decline was more rapid in people who on recruitment were: older, p = 0.0003; male, p = 0.027; had worse cognition, p < 0.0001; or carried the ε4 allele of apoliprotein E (APOEε4), p = 0.008; and after an operation if cognitive impairment was already diagnosed, p = 0.0001. Cognitive decline appears to accelerate after surgery in elderly patients diagnosed with cognitive impairment, but not other elderly patients.

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“…This opinion has been emphasized in the fields of both AD and anesthesia research. 4 The commonly used inhalation anesthetic isoflurane has been shown to induce caspase activation and apoptosis, and to increase β-amyloid protein (Aβ) oligomerization and accumulation in vitro and in vivo. [5][6][7][8][9][10][11][12][13] Desflurane, another commonly used inhalation anesthetic, may not induce these detrimental effects in cultured cells.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory

Zhang

Xie

2012

Annals of Neurology

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Objective-There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria-dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined.Methods-We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test.Results-Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript levels of mitochondrial membrane potential and adenosine-5′-triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species.Interpretation-These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria-associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation. 3 Therefore, there is a need to identify anesthetic(s) that will not induce or that will induce to a lesser degree AD neuropathogenesis and cognitive dysfunction. This opinion has been emphasized in the fields of both AD and anesthesia research. 4 The commonly used inhalation anesthetic isoflurane has been shown to induce caspase activation and apoptosis, and to increase β-amyloid protein (Aβ) oligomerization and accumulation in vitro and in vivo. [5][6][7][8][9][10][11][12][13] Desflurane, another commonly used inhalation anesthetic, may not induce these detrimental effects in cultured cells. 13,15,16 Consequently, it is important to further assess in vivo relevance, underlying mechanisms, and functional consequences (eg, learning and memory) of these observations. Therefore, we set out to determine whether isoflurane and desflurane may have different effects on learning and memory function and on mitochondrial function (eg, mitochondrial permeability transition pore [mPTP] opening).Isoflurane, but not desflurane, could induce the caspase activation and apoptosis through the mitochondria-dependent apoptosis pathway. 16 Mitochondrial dysfunction can lead to caspase activation and apoptosis, potentially through opening of mPTP, reductions in mitochond...

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Consensus Statement: First International Workshop on Anesthetics and Alzheimer’s Disease

Cited by 116 publications

References 33 publications

Preexisting Cognitive Impairment and Mild Cognitive Impairment in Subjects Presenting for Total Hip Joint Replacement

Preexisting Cognitive Impairment and Mild Cognitive Impairment in Subjects Presenting for Total Hip Joint Replacement

Cognitive decline in the elderly after surgery and anaesthesia: results from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort

Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory

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