Relationship between Surgery under General Anesthesia and the Development of Dementia: A Systematic Review and Meta-Analysis

Lee, Je Jin; Choi, Geun Joo; Kang, Hyun; Baek, Chong Wha; Jung, Yong Hun; Shin, Hwa Yong; Park, Yong‐Hee; Woo, Young Cheol

doi:10.1155/2020/3234013

Cited by 25 publications

(23 citation statements)

References 72 publications

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“…On the other hand, it has been reported that a spike of tau hyperphosphorylation happens after brain injury 76 and general anesthesia 77 , due likely to acutely diminished phosphatase activities 78 , 79 . Whether this transient tau hyperphosphorylation is related to the positive association between dementia and traumatic brain injury 13 or exposure to general anesthesia 80 remains an open question. Animal studies may provide a clue as to whether R-(−)-apomorphine can be used to neutralize hyperphosphorylated tau following brain injury or general anesthesia exposure, thus reducing the likelihood of AD and ADRD after recovery.…”

Section: Discussionmentioning

confidence: 99%

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Liu

Dexheimer

Sui

et al. 2020

Sci Rep

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The neurodegenerative Alzheimer’s disease (AD) affects more than 30 million people worldwide. There is thus far no cure or prevention for AD. Aggregation of hyperphosphorylated tau in the brain correlates with the cognitive decline of patients of AD and other neurodegenerative tauopathies. Intracerebral injection of tau aggregates isolated from tauopathy brains causes similar pathology in the recipient mice, demonstrating the pathogenic role of abnormally phosphorylated tau. Compounds controlling the aggregation of hyperphosphorylated tau therefore are probable modulators for the disease. Here we report the use of recombinant hyperphosphorylated tau (p-tau) to identify potential tauopathy therapeutics and risk factors. Hyperphosphorylation renders tau prone to aggregate and to impair cell viability. Taking advantage of these two characters of p-tau, we performed a screen of a 1280-compound library, and tested a selective group of prescription drugs in p-tau aggregation and cytotoxicity assays. R-(−)-apomorphine and raloxifene were found to be p-tau aggregation inhibitors that protected p-tau-treated cells. In contrast, a subset of benzodiazepines exacerbated p-tau cytotoxicity apparently via enhancing p-tau aggregation. R-(−)apomorphine and raloxifene have been shown to improve cognition in animals or in humans, whereas benzodiazepines were linked to increased risks of dementia. Our results demonstrate the feasibility and potential of using hyperphosphorylated tau-based assays for AD drug discovery and risk factor identification.

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Section: Discussionmentioning

confidence: 99%

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Liu

Dexheimer

Sui

et al. 2020

Sci Rep

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“…Nationwide population-based cohort studies found significant associations between GA and dementia [17,27]. However, previous meta-analyses yielded conflicting results [28][29][30]. One meta-analysis reported a significant positive association between GA and AD [30], but others found only weak or no links [28,29].…”

Section: Introductionmentioning

confidence: 99%

“…However, previous meta-analyses yielded conflicting results [28][29][30]. One meta-analysis reported a significant positive association between GA and AD [30], but others found only weak or no links [28,29]. Thus, any association between anesthesia and dementia remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Study of the Association between General Anesthesia and Increased Risk of Developing Dementia

Sohn

Lee

et al. 2021

JPM

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The association between exposure to general anesthesia (GA) and the risk of dementia is still undetermined. To investigate a possible link to the development of dementia in older people who have undergone GA, we analyzed nationwide representative cohort sample data from the Korean National Health Insurance Service. The study cohort comprised patients over 55 years of age who had undergone GA between January 2003 and December 2004 and consisted of 3100 patients who had undergone GA and 12,400 comparison subjects who had not received anesthesia. After the nine-year follow-up period, we found the overall incidence of dementia was higher in the patients who had undergone GA than in the comparison group (10.5 vs. 8.8 per 1000 person-years), with the risk being greater for women (adjusted HR of 1.44; 95% CI, 1.19–1.75) and those with comorbidities (adjusted HR of 1.39; 95% CI, 1.18–1.64). Patients who underwent GA showed higher risks for Alzheimer’s disease and vascular dementia (adjusted HR of 1.52; 95% CI, 1.27–1.82 and 1.64; 95% CI, 1.15–2.33, respectively). This longitudinal study using a sample cohort based on a nationwide population sample demonstrated a significant positive association between GA and dementia, including Alzheimer’s disease and vascular dementia.

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“…Some studies suggest a possible link between anesthesia and AD in humans [ 31 , 32 ], while more recent ones do not [ 33 , 34 ]. Also, as stated by Lee et al it is nearly impossible to discriminate the influence of general anesthesia from the effect of surgery itself on the development of AD [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Neurotoxicity of different amyloid beta subspecies in mice and their interaction with isoflurane anaesthesia

et al. 2020

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Background The aim of this study was to assess different amyloid beta subspecies’ effects on behaviour and cognition in mice and their interaction with isoflurane anaesthesia. Methods After governmental approval, cannulas were implanted in the lateral cerebral ventricle. After 14 days the mice were randomly intracerebroventricularly injected with Aβ 1–40 (Aβ40), Aβ 1–42 (Aβ42), 3NTyr10-Aβ (Aβ nitro), AβpE3-42 (Aβ pyro), or phosphate buffered saline. Four days after the injection, 30 mice (6 animals per subgroup) underwent general anaesthesia with isoflurane. A “sham” anaesthetic procedure was performed in another 30 mice (6 animals per subgroup, 10 subgroups in total). During the next eight consecutive days a blinded assessor evaluated behavioural and cognitive performance using the modified hole-board test. Following the testing we investigated 2 brains per subgroup for insoluble amyloid deposits using methoxy staining. We used western blotting in 4 brains per subgroup for analysis of tumour-necrosis factor alpha, caspase 3, glutamate receptors NR2B, and mGlu5. Data were analysed using general linear modelling and analysis of variance. Results Aβ pyro improved overall cognitive performance (p = 0.038). This cognitive improvement was reversed by isoflurane anaesthesia (p = 0.007), presumably mediated by decreased exploratory behaviour (p = 0.022 and p = 0.037). Injection of Aβ42 was associated with increased anxiety (p = 0.079). Explorative analysis on a limited number of brains did not reveal insoluble amyloid deposits or differences in the expression of tumour-necrosis factor alpha, NR2B, mGlu5, or caspase 3. Conclusions Testing cognitive performance after intracerebroventricular injection of different amyloid beta subspecies revealed that Aβ pyro might be less harmful, which was reversed by isoflurane anaesthesia. There is minor evidence for Aβ42-mediated neurotoxicity. Preliminary molecular analysis of biomarkers did not clarify pathophysiological mechanisms.

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Relationship between Surgery under General Anesthesia and the Development of Dementia: A Systematic Review and Meta-Analysis

Cited by 25 publications

References 72 publications

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Longitudinal Study of the Association between General Anesthesia and Increased Risk of Developing Dementia

Neurotoxicity of different amyloid beta subspecies in mice and their interaction with isoflurane anaesthesia

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