The Impact of Surgery and Anesthesia on Post-Operative Cognitive Decline and Alzheimer's Disease Development: Biomarkers and Preventive Strategies

Kapila, Ayush K; Watts, Helena; Wang, Tianlong; Ma, Ding

doi:10.3233/jad-132258

Cited by 75 publications

(51 citation statements)

References 141 publications

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“…Dementia is caused by a variety of diseases and injuries, such as Alzheimer's disease (AD), Parkinson's diseases, multiple sclerosis, and stroke [1,2] . Recently, surgery and anesthesia have been proposed to increase the incidence of AD [3,4] . Surgical procedures and administration of anesthesia are associated with a transient or permanent decline in cognitive function, termed postoperative cognitive dysfunction (POCD).…”

Section: Introductionmentioning

confidence: 99%

Duration-dependent regulation of autophagy by isoflurane exposure in aged rats

et al. 2015

Neurosci. Bull.

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Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer's disease (AD). Furthermore, it is also well accepted that some i nhalation anesthetics, such as isoflurane, may cause ADlike neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocampal autophagy in aged rats. Aged Sprague-Dawley rats (20 months old) were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze (4 trials/day for 5 consecutive days). Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B (LC3B), as well as p62, an indicator of autophagic fl ux, were quantifi ed by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3B-II, and p62 at 24 h post-anesthesia between the 1-h isoflurane-exposed rats and their controls (P >0.05). Four-hour exposure to isofl urane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 postanesthesia and less time spent in the target quadrant than sham-exposed animals (P <0.05). These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isofl urane (P <0.01 and P <0.05). Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isofl urane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease w ithin 12-24 h post-anesthesia (P <0.05). Hippocampal p62 p eaked at 6 h but subsequently resolved. These results from our pilot in vivo study support a durationdependent relationship between 1.5% isoflurane exposure, and s patial cognitive function as well as hippocampal phagophore formation.

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Section: Introductionmentioning

confidence: 99%

Duration-dependent regulation of autophagy by isoflurane exposure in aged rats

et al. 2015

Neurosci. Bull.

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“…The deterioration and impairment of central cholinergic system is not only related to normal aging (33), but also to neurodegenerative diseases such as AD (20). Cholinesterase inhibitors have been shown to improve cognitive function (20). Several clinical studies showed that drugs with anti-cholinergic effects had negative effects on the cognitive function of patients (33)(34)(35).…”

Section: Mechanismsmentioning

confidence: 99%

“…Cholinergic pathway participates in various cognitive processes including short-term memory, learning and attention (33). The deterioration and impairment of central cholinergic system is not only related to normal aging (33), but also to neurodegenerative diseases such as AD (20). Cholinesterase inhibitors have been shown to improve cognitive function (20).…”

Section: Mechanismsmentioning

confidence: 99%

“…Many studies investigating the mechanisms and biomarkers of POCD have resorted to the same ones of AD. Review articles of POCD tended to discuss them together when introducing the mechanisms and intervention of the mentioned diseases (20,36). Recently, studies have focused on trying to find biomarkers that can predict POCD before surgery (23,37,38).…”

Section: Mechanismsmentioning

confidence: 99%

“…The possible mechanisms of POCD investigated included platelet activation (17), oxidative stress (18), cholinergic function impairment (19,20), impairment of synaptic integrity (2,21), similar mechanisms of Alzheimer's disease (AD) such as beta-amyloid accumulation (22,23) and tau phosphorylation (24), and immune response and inflammation related mechanisms such as the bone marrow-derived macrophages recruitment in hippocampal area (25) and the recent popular surgery-induced neuroinflammation (12,26,27) (Table 2).…”

Section: Mechanismsmentioning

confidence: 99%

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Difficulties in Understanding Postoperative Cognitive Dysfunction

An¹,

Yu²

2017

J Anesth Perioper Med

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Aim of review:Firstly brought up by Bedford in 1955, postoperative cognitive dysfunction (POCD) has been given increasing attention due to the increase of the elderly population. Although many researches have been conducted on POCD, the understanding of this clinical syndrome is still limited. There are currently many disputes regarding almost every aspects of POCD, even the term itself has not been included in the MeSH Database. This review aims to discuss the major disputes about POCD that hinder research consistency and provide possible perspectives for future research. Method: Recent articles and literatures about POCD were searched and reviewed. First, basic knowledge of POCD, including characteristics and incidence, risk factors, mechanisms, prevention and intervention are introduced. Second, the major obstacles of investigating POCD are discussed. Then two major problems are proposed: 1) Does the POCD in patients really start postoperatively? 2) Is POCD only related to old age? Finally, the never-ending argument regarding the role of anesthesia on POCD is discussed. Recent findings: Recent researches regarding POCD focused on the surgery-related neuroinflammation mechanism, and efforts have been made to find some biomarkers of POCD. In terms of POCD, there are many fundamental concepts and in urgent need of consensus. First, unifying the terms used among studies will benefit the communication of knowledge. Second, questions like whether POCD should be defined as a general cognitive decline that include other forms such as postoperative delirium, or they should be considered as separate unique illnesses, and whether or not young patients should be included when POCD is discussed, need to be answered. Only after answering these questions, will the study of POCD be less disputable. Third but not the least, efforts should be made trying to make "golden-standard" in regard of the testing methods of POCD both clinically and pre-clinically. Summary: Although lots of researches have been conducted on POCD, the understanding of this clinical syndrome is still very limited. There are currently many disputes regarding almost every aspect of POCD. It's time for clinicians and scholars to strike some fundamental consensus for the better investigation of POCD. How to find a way to increase the rigor of experimental design is an important question that still seeks answers.

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Plasma Biomarkers of Tau and Neurodegeneration During Major Cardiac and Noncardiac Surgery

et al. 2021

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Major surgery is often complicated by postoperative neurocognitive disorder. Affected patients exhibit problems with memory and executive function, similar to deficits seen in Alzheimer disease (AD). 1,2 A critical question is whether surgery can exacerbate or unmask latent pathophysiology underlying the development of AD. 2 Plasma biomarkers of neuronal damage including total tau and neurofilament light chain (NfL) suggest that surgery can trigger injury. 3 Unlike total tau and NfL levels that increase in different brain disorders, the plasma level of tau protein phosphorylated at threonine residue 181 (pTau181) is relatively specific and predictive of AD. 4 Whether major surgery triggers increases in plasma pTau181 is unknown.Lowest core temperature, °C 35.5 (35.0-35.9) 28.1 (28.0-35.3) Cardiopulmonary bypass duration, min NA 183 (63-512) Circulatory arrest NA 3 Yes, 3 no Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); NA, not applicable.

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The Impact of Surgery and Anesthesia on Post-Operative Cognitive Decline and Alzheimer's Disease Development: Biomarkers and Preventive Strategies

Cited by 75 publications

References 141 publications

Duration-dependent regulation of autophagy by isoflurane exposure in aged rats

Duration-dependent regulation of autophagy by isoflurane exposure in aged rats

Difficulties in Understanding Postoperative Cognitive Dysfunction

Plasma Biomarkers of Tau and Neurodegeneration During Major Cardiac and Noncardiac Surgery

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