Advances in research on the pathogenesis and signaling pathways associated with postoperative delirium (Review)
- Authors:
- Published online on: June 3, 2025 https://doi.org/10.3892/mmr.2025.13585
- Article Number: 220
-
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
Introduction
Surgery is a fundamental approach to disease treatment and prevention, carrying out a vital role in enhancing the quality of life of patients and driving economic growth. The continuous advancements in surgical and anesthetic techniques have led to a steady increase in global surgical procedures, with annual operations now at >300 million (1). However, this growing surgical volume also brings heightened concerns regarding postoperative complications, making their prevention, management and prognosis key priorities for medical professionals. Among these, perioperative neurocognitive disorders are among the most prevalent neurological complications (2), with an incidence rate of 50% (3), adversely affecting both short-term recovery and long-term health, particularly in elderly patients (4). With the aging Chinese population, the number of elderly individuals undergoing anesthesia and surgery is steadily increasing. Currently, elderly patients account for more than 30% of all surgical cases in China (5), which has further intensified concerns about perioperative neurocognitive disorders and highlighted the necessity for effective management strategies.
In 2018, the Perioperative Cognition Nomenclature Working Group, composed of multidisciplinary experts, redefined delirium as an acute and transient brain dysfunction characterized by attention deficits, memory impairment, fluctuations in consciousness levels, disorganized thinking, sleep cycle disturbances and mood disorders (6). Among its various subtypes, postoperative delirium (POD) is specifically defined as an acute episode that meets the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th edition criteria for delirium and occurs within 1 week after surgery or before hospital discharge (7). POD exhibits a time-related pattern, with its occurrence mainly observed between postoperative days 1 and 3 (6). Notably, identifying and diagnosing POD in clinical practice is challenging for several reasons. First, 50% of POD cases present as low-activity types, characterized by quietness, silence, slow movements, drowsiness and reduced interaction. These atypical clinical symptoms are often overlooked by healthcare staff. Second, the lack of formal assessment strategies exacerbates the difficulty in diagnosis. The DSM is considered the gold standard for diagnosing POD, but its clinical application is limited by resource and time constraints (8). As a result, clinicians may opt for shorter assessment tools, such as the Intensive Care Unit Confusion Assessment Method (9) or the Nursing Delirium Screening Scale (10), although this often comes at the cost of sensitivity (11–13). Prioritizing high specificity over sensitivity can lead to a subset of patients with delirium being missed. While POD is difficult to recognize and diagnose, its consequences are severe, encompassing increased complication rates, impaired postoperative recovery, prolonged hospital stays, heightened healthcare costs, greater risk of hospital readmission and elevated mortality (14). Furthermore, accumulating evidence suggests that POD, as a hallmark of acute postoperative cognitive dysfunction, serves as a precursor to long-term cognitive impairment (15–17). Specifically, POD has been associated with persistent brain dysfunction, including progressive cognitive decline and an increased risk of dementia. These findings underscore the need for early identification and effective management strategies to mitigate the long-term impact of POD on cognitive health.
By contrast, postoperative cognitive decline (POCD) typically emerges at the end of the first postoperative week and does not affect the level of consciousness of the patient. This distinction was highlighted by Glumac et al (18), who demonstrated that POCD and POD present temporally and clinically distinct phenomena. Differentiating between the two is key as they differ in onset, pathophysiology, clinical course, prognosis, and management approaches. POD is characterized by an acute onset, fluctuating course, and potential reversibility with prompt intervention, whereas POCD presents more insidiously, may persist for weeks or months, and currently lacks standardized treatment protocols. Failure to distinguish between them may result in misdiagnosis, inappropriate management, and inaccurate interpretation of clinical or research findings. Therefore, the aim of the present review was to summarize advances in understanding the pathogenesis and signaling pathways of POD, and to explore current strategies for its prevention and treatment.
Literature search
The present review was conducted to summarize the current evidence on the pathogenesis, signaling pathways and strategies for the prevention and treatment of POD. A comprehensive literature search was carried out using the PubMed database (pubmed.ncbi.nlm.nih.gov/) for studies published up to January 2025. The search strategy included the following key words: ‘Postoperative delirium’, ‘POD’, ‘cognition disorders’, ‘pathogenesis’, ‘signal transduction’, ‘prevention’ and ‘treatment’. Boolean operators (AND and OR) were used to refine the search. Only articles published in English were considered. Both clinical studies and animal studies were included if they contributed to understanding the mechanisms or management of POD. The initial search and selection of studies were independently conducted by three authors (RHB, LL and XMD). The final list of included studies was reviewed and approved by WQL.
Pathogenesis of POD
The occurrence of POD results from multiple interacting factors and is influenced by preoperative, intraoperative and postoperative conditions. Despite extensive research, the underlying mechanisms of POD remain incompletely understood. Numerous studies suggest that its pathogenesis may involve neurodegenerative changes, neuroinflammation, sleep disturbances, neurotransmitter imbalances, β-amyloid (Aβ) deposition and excessive tau protein phosphorylation (19–22). In addition to these mechanisms, emerging evidence indicates that gut microbiota can regulate cognitive function via the microbiota-gut-brain axis (23). Furthermore, sensory impairments, including deficits in vision, hearing and olfaction, have also been associated with postoperative neurocognitive disorders (24,25). Notably, these mechanisms intersect, interact and collectively contribute to the development of POD (Fig. 1).
Degenerative changes in brain structure and function
Brains are highly energy-demanding organs that require sufficient energy to sustain normal functional activities (26). A decline in brain metabolism has been implicated in the development of POD (27). Specifically, during delirium episodes, cortical glucose metabolism is markedly reduced, with partial recovery observed as delirium symptoms subside. In support of this, Caplan et al (28) observed increased anaerobic metabolism in the brains of patients with delirium, characterized by elevated cerebrospinal fluid lactate levels and decreased neuron-specific enolase concentrations, suggesting metabolic stress. Furthermore, with aging, pathological and physiological changes occur in cerebral blood vessels, leading to impaired brain perfusion and vascular reactivity (29,30). Multiple studies have demonstrated that reduced cerebral perfusion may contribute to cognitive and learning impairments. For instance, using computed tomography, Yokota et al (31) and Aa et al (32) identified notably decreased cerebral perfusion in patients with delirium, which returned to normal following symptom resolution. Consistently, numerous studies have confirmed that individuals with preoperative cognitive impairment or diminished cognitive reserve, such as those with dementia or mild cognitive impairment, are at a higher risk of developing POD after surgery (33–35).
Neuroinflammation
Neuroinflammation is a key characteristic of all neurological complications (20). Surgical procedures cause extensive tissue damage, ischemia-reperfusion injury and hypoperfusion due to pronounced blood loss. These factors collectively lead to the excessive release of inflammatory mediators, triggering a systemic inflammatory response that impairs multiple organ functions, including those of the brain (36,37). One major consequence of this inflammatory cascade is the disruption of the blood-brain barrier (BBB). The excessive release of C-reactive protein and pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, damages endothelial cells, reduces the expression of tight junction proteins and increases BBB permeability (38). As a result, peripheral inflammatory mediators infiltrate the brain parenchyma, further enhancing the activation of microglia and astrocytes. Once activated, microglia perpetuate neuroinflammation by producing nitric oxide, which leads to DNA deamination and neuronal apoptosis, as well as the production of reactive oxygen species, which causes lipid peroxidation (30,37,39). These processes collectively contribute to neuronal and synaptic dysfunction, ultimately promoting the development of POD. In addition to direct neuronal damage, surgery-induced neuroinflammation negatively impacts neuroplasticity; it downregulates brain-derived neurotrophic factor (BDNF) and its receptors, inhibiting downstream signaling pathways essential for neurogenesis, synaptogenesis, learning and memory (36). Moreover, a study has revealed that surgical stress disrupts hippocampal iron homeostasis, leading to iron accumulation. This iron overload exacerbates oxidative stress, intensifies neuroinflammation and further impairs cognitive function (40). Supporting this inflammatory hypothesis, a study by Glumac et al (41) demonstrated that preoperative corticosteroid administration effectively attenuates the systemic inflammatory response and improves postoperative cognitive outcomes, highlighting inflammation as a key factor in the pathogenesis of POD.
Accumulation of Aβ and tau hyperphosphorylation
Extracellular Aβ plaques, tau hyperphosphorylation and neurofibrillary tangles (NFTs) formed by tau aggregation are major pathological hallmarks of neurodegenerative diseases, particularly Alzheimer's disease (AD) (42). Studies suggest that POD shares a similar pathological basis with AD (43,44). Aβ protein readily aggregates in brain tissue, forming highly toxic oligomers that induce neuronal death and synaptic damage. Moreover, Aβ oligomers disrupt central nervous system insulin signaling, thereby interfering with brain energy metabolism and further exacerbating neurodegeneration (45). Tau protein, a microtubule-associated protein, plays a key role in microtubule assembly, stabilization and axonal transport; it is essential for regulating neuronal growth, development and signal transmission (42,44). However, surgery and anesthesia have been revealed to induce tau hyperphosphorylation, leading to structural and functional abnormalities (46,47). Hyperphosphorylated tau proteins further aggregate and precipitate, forming NFTs, which are sensitive biomarkers of axonal injury in the central nervous system (48,49). Notably, elevated levels of NFTs in cerebrospinal fluid and blood have been associated with POD (50). Aβ and abnormally phosphorylated tau proteins act synergistically to influence the onset and progression of POD. Aβ oligomers promote tau phosphorylation by increasing GSK-3β activity. Additionally, both of them collectively activate microglia and astrocytes, triggering the release of various inflammatory cytokines (51–53). These inflammatory mediators further accelerate tau hyperphosphorylation and Aβ oligomerization, ultimately leading to neuronal damage and the development of POD.
Sleep disorder
Sleep is key for neurodevelopment and the maintenance of brain function. Studies suggest that perioperative sleep disturbances are associated with the occurrence of POD (54–56). Various perioperative factors, including trauma, anesthesia, stress, pain and inflammation, can disrupt the sleep-wake regulatory system and circadian rhythm, further contributing to postoperative neurocognitive dysfunction. Multiple studies have demonstrated that patients with delirium exhibit a pronounced reduction in the rapid eye movement phase of sleep, increased sleep fragmentation and heightened wakefulness (57–59). Sleep disturbances lead to hyperactivation of the hypothalamic-pituitary-adrenal axis, resulting in excessive cortisol secretion. Elevated cortisol levels inhibit neuronal glucose uptake, making neurons metabolically vulnerable to oxidative stress. This process contributes to neuronal loss, alterations in dendritic spine density and changes in synaptic number, morphology and function, ultimately leading to cognitive impairment (56,60,61). Additionally, sleep deprivation increases the release of inflammatory cytokines, activates microglia and exacerbates neuroinflammatory responses (62,63). Fultz et al (64) further revealed that disruptions in the sleep-wake cycle dysregulate aquaporin-4 expression levels, impairing the glymphatic system and hindering cerebrospinal fluid clearance of Aβ protein. These pathological changes suggest that disturbances in the sleep-wake cycle contribute to POD development through multiple interrelated pathways. Notably, in patients of postoperative cardiac surgery, sleep deprivation consistently precedes the onset of delirium. Furthermore, patients in the ICU experiencing sleep deprivation are markedly more likely to develop delirium compared with those with adequate sleep (65).
Olfactory-brain association mechanism
Olfactory signals are transmitted via the olfactory filaments, olfactory bulb and olfactory tract to the primary olfactory cortex, from where they further project to brain regions, including the insula, hypothalamus and hippocampus (66). Notably, certain olfactory centers and the hippocampus exhibit synchronized electrophysiological activity and directly participate in memory processes, highlighting the functional interplay between olfaction and cognition (67). Emerging evidence suggests that anesthesia and surgery can impair both olfactory and cognitive functions. Zhang et al (24) revealed that anesthesia and surgery lead to deficits in olfaction and cognition in mice, while olfactory stimulation reverses these effects by restoring the expression of olfactory marker protein 13 and growth-associated protein 43, and by preventing the reduction of hippocampal synaptic markers postsynaptic density protein (PSD)-95 and synaptophysin. Clinical studies further support this finding. Kamath et al (68) discovered that preoperative olfactory dysfunction is associated with both the incidence and severity of POD, suggesting that olfactory assessment could serve as a valuable preoperative screening tool for identifying high-risk patients with POD. Similarly, in the study by Yang et al (69), 14 out of 21 (66.67%) patients with preoperative olfactory dysfunction exhibited postoperative cognitive dysfunction, providing additional evidence of the association between olfactory function and cognitive performance. Mechanistically, research has indicated that olfactory and cognitive processing centers share overlapping neural pathways, with the cholinergic system carrying out a central role in both olfactory transmission and cognitive function. Dopamine and acetylcholine serve as key neurotransmitters regulating both cognition and olfaction. Given these interconnections, olfactory impairment may contribute to the development of POD by disrupting shared neurochemical and neural circuits (70,71).
Gut microbiota dysbiosis
Previous studies have revealed that alterations in gut microbiota are associated with abnormal cognitive behaviors. The gut microbiota carries out a key role in regulating neural functions in the brain through multiple pathways, including immune modulation and neuroendocrine regulation, thereby influencing cognitive processes (72–74). Anesthesia and surgery induce gut microbiota dysbiosis, which is primarily characterized by a notable reduction in microbial abundance and diversity, particularly with aging (75). This dysbiosis exacerbates systemic inflammation, increases gut permeability and subsequently compromises the integrity of the BBB, ultimately leading to disruptions in brain immune homeostasis. Furthermore, gut microbiota can produce Aβ protein, which, despite having a different primary structure from brain-derived Aβ, shares a highly similar tertiary structure. This structural similarity suggests that gut microbiota dysbiosis may contribute to the abnormal deposition of Aβ and tau proteins, potentially triggering cross-immune reactions and excessive activation of pro-inflammatory signaling pathways in the brain (76). In addition to its role in protein aggregation, gut microbiota dysbiosis also alters neurotransmitter levels, including γ-aminobutyric acid, 5-hydroxytryptamine, dopamine and acetylcholine, thereby affecting central nervous system function (74,77). Notably, disruptions in gut microbiota composition can induce neuropsychiatric symptoms such as anxiety and depression, which may accelerate cognitive decline by further impairing neural function (78,79).
Electroencephalography (EEG) burst suppression hypothesis
EEG burst suppression is a common neurophysiological phenomenon observed during clinical anesthesia, characterized by alternating high-amplitude burst activity and periods of isoelectric suppression on EEG. Notably, the occurrence of POD is associated with the depth of general anesthesia, as excessive anesthetic depth increases the likelihood of EEG burst suppression, which in turn elevates the risk of POD (80). Clinical studies have demonstrated this association (81–83). In a study of spinal fixation surgery under total intravenous anesthesia, 78 patients (69.6%) exhibited intraoperative burst suppression (BS), while 10 patients (8.9%) developed POD. All cases of POD occurred in patients who experienced intraoperative BS, and prolonged BS duration was observed in these individuals (84). Further research has indicated a quantitative relationship between BS duration and risk of POD, with each additional minute of intraoperative BS doubling the likelihood of developing POD. Given this evidence, intraoperative BS has been proposed as a potential predictor of POD, highlighting the importance of anesthetic depth monitoring to mitigate the risk of POD (85).
Genetic susceptibility
In recent years, the genetic hypothesis of delirium susceptibility has emerged as a promising research direction. Studies have identified associations between POD and several genetic factors, including APOE4, the dopamine transporter gene SCL6A3, the dopamine receptor 2 gene, the glucocorticoid receptor, the melatonin receptor and mitochondrial DNA haplotypes (86–88). Additionally, two long intergenic non-coding RNA genes with potential functional implications have been revealed, further expanding the understanding of the genetic basis of POD (89).
POD-related signaling pathways
Given the multifaceted pathogenesis of POD, numerous interconnected signaling pathways are implicated, including the Wnt/β-catenin, PI3K/AKT, BDNF/tropomyosin receptor kinase B (TrkB), toll-like receptor (TLR) and NF-κB pathways (90) (Fig. 2).
Wnt/β-catenin signaling pathway
The Wnt signaling pathway consists of one canonical and two non-canonical pathways, which enhance synaptic plasticity, promote neuronal survival and regulate cell death, thereby carrying out a key role in brain function (91). Notably, studies have revealed that the canonical Wnt/β-catenin pathway is involved in the pathogenesis of POD. In a study on Sprague-Dawley rats, exposure to 3% sevoflurane for 6 h resulted in cognitive impairment, downregulation of β-catenin and phosphorylated GSK-3β in the hippocampus, increased levels of TNF-α and IL-1, and structural damage to hippocampal neurons. These findings suggest that sevoflurane suppresses Wnt/β-catenin signaling, activates inflammatory responses and induces hippocampal injury, ultimately contributing to POD development (92). Notably, this damage was reversed upon exogenous administration of lithium chloride, an activator of the Wnt/β-catenin pathway. Further supporting the role of Wnt/β-catenin signaling in POD, a study on endothelial cells have shown that exposure to 3% sevoflurane for 6 h downregulates Wnt/β-catenin activity, leading to reduced Annexin A1 expression, disruption of the BBB and subsequent POD onset (93). Similarly, in transgenic mice, overexpression of DKK-1 inhibits the Wnt/β-catenin pathway, promoting excessive tau protein phosphorylation and cognitive impairment. Conversely, activation of the Wnt/β-catenin pathway suppresses inflammatory responses and improves cognitive function, suggesting its potential as a therapeutic target for POD prevention and treatment (94).
PI3K/AKT signaling pathway
Key roles are conducted by the PI3K/AKT signaling pathway, including cell growth, proliferation, differentiation and apoptosis. PI3K functions as a key intracellular signaling molecule, while AKT serves as its primary downstream protein kinase. Upon activation, PI3K further phosphorylates AKT, which in turn further phosphorylates key downstream targets, including GSK-3β, mTOR, endothelial nitric oxide synthase, FoxO3a and NF-κB, thereby regulating physiological processes such as cell growth, proliferation, cell cycle progression and glucose metabolism (95,96).
PI3K/AKT/GSK-3β
GSK-3 is a key substrate of AKT and exists in two isoforms in the brain: GSK-3α and GSK-3β. Among them, GSK-3β is widely expressed in the central nervous system and is implicated in the pathological mechanisms underlying cognitive decline in neurodegenerative diseases (96). GSK-3β is a key kinase responsible for tau phosphorylation. Both animal and clinical studies have demonstrated a positive association between the abnormal upregulation of GSK-3β, tau phosphorylation and the accumulation of toxic tau aggregates (97–99). Notably, increased levels of GSK-3β and phosphorylated tau have been observed in rodent brain tissues following anesthesia and surgery, further supporting its role in postoperative neurocognitive impairment. Beyond tau pathology, GSK-3β activation has been revealed to contribute to Aβ formation and accumulation in the brain by regulating amyloid precursor protein cleavage (51). Additionally, it can induce Aβ pathology by disrupting insulin signaling pathways (100). Studies have proposed a feedback loop between Aβ and GSK-3β activation, where sustained interactions in specific pathways may exacerbate tau hyperphosphorylation and neurotoxicity (101–103). GSK-3β is also involved in neuroinflammation. The activation of GSK-3β promotes the production of IL-1, IL-6 and TNF-α, activates the JNK, STAT3/5, and NF-κB signaling pathways, and regulates microglial migration, contributing to inflammatory responses in the brain (104). Furthermore, GSK-3β has been implicated in the suppression of adult hippocampal neurogenesis. The excessive activation of GSK-3β impairs long-term potentiation and enhances N-methyl-D-aspartate receptor-dependent long-term depression, thereby disrupting synaptic plasticity, memory formation and neurogenesis. These mechanisms collectively suggest that GSK-3β overactivation may play a key role in the pathogenesis of POD (51).
PI3K/AKT/mTOR
mTOR is an atypical serine/threonine kinase that plays a key role in cell growth, proliferation, protein synthesis and autophagy. As a major downstream target of the PI3K/AKT signaling pathway, mTOR serves as the principal negative regulator of autophagy, a process essential for cell survival, development, division and homeostasis (105). Autophagy has a dual role in neural function. First, it facilitates the clearance and degradation of Aβ protein. In both cellular and animal models, autophagy activators, such as mTOR inhibitors, have been revealed to reduce tau hyperphosphorylation and the misfolding of other aggregated proteins by promoting the autophagic degradation of NFTs and Aβ plaques (106). Secondly, autophagy is involved in synaptic plasticity and neurotransmission, highlighting its broader role in cognitive function.
Gao et al (107) demonstrated that anesthesia and surgery impair reference memory while inducing mTOR activation, as evidenced by increased levels of phosphorylated mTOR and decreased expression of autophagy-related proteins such as Beclin-1 and LC3-II. Additionally, neuronal and synaptic plasticity-associated proteins (such as Synaptophysin and PSD-95) were downregulated. Notably, pretreatment with rapamycin suppressed mTOR activation, restored autophagy and reversed anesthesia/surgery-induced learning and memory deficits. Despite its beneficial roles, excessive autophagy can be detrimental, as it may disrupt normal organelle function, leading to cellular dysfunction or cell death. The PI3K/AKT/mTOR signaling pathway exerts bidirectional effects on neuronal cells, where both overactivation and inhibition can contribute to cognitive decline (96,108). Pharmacological modulation of this pathway has demonstrated promise in protecting cognitive function. Dexmedetomidine and esketamine activate the PI3K/AKT/mTOR pathway, alleviating neuroinflammatory responses in brain tissue, inhibiting neuronal apoptosis and ultimately preserving postoperative cognitive function (109,110).
The PI3K/AKT signaling pathway has been extensively studied in neurological diseases, with numerous associated pathways being explored. In addition to those previously discussed, other pathways, such as PI3K/AKT/Nrf2, PI3K/AKT/CREB and PI3K/AKT/MAPK, have been identified. These interconnected pathways regulate a range of neurophysiological and pathological processes, including mitochondrial function restoration, abnormal protein clearance, cerebrovascular regeneration and synaptic plasticity enhancement (111–113).
BDNF/TrkB signaling pathway
BDNF is the most abundant neurotrophic factor in the brain, playing a key role in regions responsible for learning, memory and higher cognitive functions, such as the hippocampus, cerebral cortex and basal forebrain (114). Dysregulation of BDNF and its downstream pathways may lead to abnormal neuronal differentiation, synaptic loss and cognitive dysfunction, suggesting that the BDNF/TrkB signaling pathway may be involved in the pathogenesis of POD. Qiu et al (115) demonstrated that anesthesia and surgery induce microglial activation, IL-1β release and BDNF downregulation in the hippocampus, resulting in hippocampus-dependent cognitive impairment in aged mice. Subsequent studies have also reported a notable reduction in total TrkB expression (114,116,117). Similarly, Fan et al (118) revealed that surgery reduces BDNF expression and neurogenesis while also decreasing phosphorylated/activated TrkB and ERK expression. However, this study observed no significant impact on total TrkB expression levels. This discrepancy may be attributed to differences in surgical procedures, mouse age and tissue collection time points. In addition to its role in neurogenesis, the BDNF/TrkB pathway is also key for synaptic plasticity and neuronal growth. Notably, the BDNF/proBDNF ratio carries out a key role in regulating synaptic plasticity (119). Jia et al (117) revealed that exposure to 3% sevoflurane markedly inhibited the proliferation of neural stem cells, immature neurons and newly formed neurons, which was accompanied by reduced BDNF and TrkB protein expression. Furthermore, studies have suggested that the BDNF/TrkB signaling pathway is involved in Aβ aggregation and tau protein phosphorylation (119–121). Activation of this pathway has been revealed to reduce tau phosphorylation levels and enhance learning and memory abilities, highlighting its potential as a therapeutic target for neurodegenerative diseases and POD.
TLR signaling pathway
TLR signaling involves at least two distinct pathways: The MyD88-dependent and MyD88-independent pathways (122). The MyD88-dependent pathway is the primary TLR signaling cascade, transmitting signals through two major activation routes: The MAPK and NF-κB pathways. Both pathways regulate the transcription of inflammatory factors, leading to excessive cytokine release, which ultimately affects the central nervous system and contributes to cognitive dysfunction (123). Among the TLR family, TLR4 is highly expressed in microglial cells and serves as a key receptor for microglial activation and function (122). Lu et al (124) subjected rats to tibial fracture surgery and observed increased expression of S100A8 and S100A9, along with hippocampal TLR4/MyD88 activation. This pro-inflammatory response was associated with the onset of POD. Similarly, in aged rats undergoing splenectomy, TLR4 activation was detected, accompanied by elevated levels of inflammatory mediators such as IL-6 and IL-1β, which triggered central neuroinflammation (125). Beyond TLR4, other TLR family members have also been implicated in surgery-induced neuroinflammation and cognitive dysfunction. Lin et al (126) conducted anesthesia and surgery on both TLR2-knockout and wild-type mice, assessing their learning and memory abilities. The findings suggested that TLR2 contributes to surgery-induced neuroinflammation and cognitive impairment. A study by Yang et al (127) demonstrated that inhibition of the TLR2/TLR4 signaling pathway suppresses hippocampal neuroinflammatory cytokines and alleviates postoperative cognitive dysfunction in rats. Chen et al (128) revealed that extracellular RNAs-TLR3 carries out a role in learning and memory deficits following nephrectomy in mice. Additionally, a recent study indicated that TLR7 is involved in anesthesia- and surgery-induced cognitive dysfunction (129). Collectively, these findings suggest that TLR signaling pathways carry out a key role in the development of POD, highlighting their potential as therapeutic targets for intervention.
MAPK signaling pathway
The MAPK signaling pathway mediates specific biological functions such as cell proliferation, differentiation and survival, encompassing the p38 MAPK pathway, the JNK pathway and the ERK pathway (130).
p38 MAPK pathway
p38 MAPK, also known as a stress-activated protein kinase, regulates key cellular processes, including cell proliferation, differentiation, survival and stress-induced apoptosis. Evidence suggests that its dysregulation carries out a key role in cognitive impairment and neuroinflammation (131). Lv et al (132) demonstrated that mice subjected to exploratory laparotomy exhibited cognitive deficits, with both pathological analysis and western blotting results consistently demonstrating increased phosphorylated (p)-p38 expression. Similarly, Song et al (131) conducted a study on neonates exposed to sevoflurane and found a time-dependent upregulation of p-p38 and p-p65, as well as the p-p38/p38 and p-p65/p65 ratios. Beyond its involvement in neuroinflammatory responses, p38 MAPK directly modulates GSK-3β activity, leading to increased GSK-3β kinase function, which in turn promotes tau hyperphosphorylation and impairs synaptic plasticity (133). Studies have demonstrated that activation of the p38 MAPK signaling pathway contributes to the onset of POD (131–133). Conversely, inhibition of p-p38 expression has been revealed to mitigate POD symptoms (134).
JNK pathway
The JNK pathway has a key role in transmitting extracellular signals to the nucleus and is involved in various biological processes, including cytokine regulation and inhibition of protein synthesis (135). JNK is classified into three isoforms: JNK1, JNK2 and JNK3. Among them, JNK3 is highly expressed and activated in the brain tissue and cerebrospinal fluid of patients with delirium, with a notable association with the rate of cognitive decline (136). In a study by Li et al (137), exposure to isoflurane led to increased expression of p-JNK and p-c-Jun, suggesting that JNK pathway activation contributes to isoflurane-induced neuroapoptosis in the developing brain. Similarly, Bi et al (138) revealed that sevoflurane activates the JNK/c-Jun/AP-1 signaling pathway, which in turn upregulates the apoptotic factor connexin 43, leading to neuronal apoptosis. Yang et al (139) noted that JNK signaling may have a key role in the reduced survival rate of fetal neural stem cells induced by sevoflurane. Notably, inhibition of the JNK pathway has been revealed to mitigate neuronal apoptosis and exert neuroprotective effects (140).
ERK pathway
ERK is a key regulator of pro-inflammatory microglial activation, and its signaling pathway carries out a key role in reducing oxidative stress and exerting neuroprotective effects in POD (141). The ERK phosphorylation status is associated with anesthesia-induced neurotoxicity. Yufune et al (142) observed that oxidative stress-mediated inhibition of ERK phosphorylation serves as a fundamental mechanism underlying sevoflurane-induced neurotoxicity. Numerous studies have demonstrated that anesthetics such as sevoflurane, ketamine and propofol suppress the ERK1/2 signaling pathway, leading to neuronal apoptosis in the developing brain (143–145). Conversely, certain studies have confirmed that restoring ERK phosphorylation can counteract anesthetic-induced neuronal apoptosis (143–146). Lithium, N-stearoyl-L-tyrosine, the phosphodiesterase-4 inhibitor, roflumilast, and electroacupuncture pretreatment have all been demonstrated to attenuate anesthetic-induced neuronal apoptosis and improve cognitive function by upregulating ERK signaling. Several studies have underscored the key role of the ERK signaling pathway in neuronal growth, survival and synaptic plasticity (147,148).
NF-κB signaling pathway
NF-κB is a transcription factor that has a key role in various physiological processes, including the immune response, cell proliferation and growth, synaptic plasticity and cell survival. NF-κB activation may also be associated with neuroinflammation and cognitive impairment, particularly in the context of surgery and anesthesia. Surgical procedures and anesthetic exposure trigger the release of endogenous factors such as high mobility group box 1 and TNF-α, which activate NF-κB translocation into the nucleus. This activation promotes the transcription of target genes, leading to the release of inflammatory mediators and inducing a neuroinflammatory response (149,150). Additionally, key contributors to neuroinflammation, including neutrophils, macrophages, T cells and glial cells, further amplify this inflammatory cascade via NF-κB signaling (149). Notably, activation of the NF-κB signaling pathway has been observed in various animal models of POD, reinforcing its role in postoperative neuroinflammation. Liu et al (151) observed a marked increase in p-NF-κB and p65 levels following exploratory laparotomy in mice, which was accompanied by a reduction in the BBB-associated proteins, zonula occludens protein-1, occludin and claudin-5, in the hippocampus. These findings indicate that NF-κB activation compromises BBB integrity, thereby contributing to POD pathogenesis. NF-κB activation is also associated with various forms of neuronal death. Li et al (152) and Wang et al (153) demonstrated that surgery and anesthesia induce neuronal apoptosis via NF-κB signaling activation, while Dai et al (154) reported that repeated sevoflurane exposure in neonatal mice leads to NF-κB-mediated neuronal pyroptosis. This process disrupts neuronal architecture and connectivity, ultimately impairing cognitive function. Given its key role in neuroinflammation and neuronal damage, targeting NF-κB signaling inhibition may serve as a promising therapeutic approach for POD treatment (155,156).
In addition to the aforementioned pathways, several other signaling cascades have been implicated in the pathogenesis of POD, including the NLRP3 inflammasome, JAK/STAT, Notch and AMP-activated protein kinase pathways (157). Rather than acting in isolation, these pathways engage in extensive crosstalk and dynamic interactions, collectively shaping the onset and progression of POD. For instance, activation of the Wnt/β-catenin pathway enhances PI3K/AKT signaling, which in turn upregulates the BDNF/TrkB pathway which is key for promoting neuronal survival, synaptic plasticity and overall neuroprotection (158). Conversely, pro-inflammatory signaling routes such as TLR and NF-κB may antagonize these protective mechanisms. TLR activation facilitates NF-κB nuclear translocation and the induction of pro-inflammatory cytokines, thereby compromising BBB integrity and suppressing the BDNF expression levels, both of which impair synaptic function (159). Moreover, dysregulated PI3K/AKT signaling may further amplify NF-κB activity, while NF-κB can also be activated downstream of MAPK signaling, establishing a positive feedback loop that exacerbates neuroinflammation (160). These antagonistic interactions between neuroprotective and inflammatory pathways reflect a dynamic imbalance in signal transduction, which may underlie the molecular pathology of POD. A deeper understanding of the interactions among these signaling pathways may provide a theoretical basis for elucidating the molecular mechanisms of POD and for developing multi-target therapeutic strategies.
Prevention and management of POD
Although the incidence of POD is high, studies indicate that up to 40% of cases are preventable and the majority of patients experience recovery once the underlying causative factors are addressed (161,162). Therefore, early prediction, identification and diagnosis in clinical practice, combined with timely and effective interventions, are essential for reducing the incidence of POD, particularly in elderly patients.
Several studies support the use of non-pharmacological approaches for the prevention of POD (69,163–176). Among these, cognitive training is a particularly effective intervention that enhances preoperative cognitive reserve and has been demonstrated to reduce the incidence of POD in elderly patients (163–165). With technological advancements, more accessible computer-based cognitive training programs have emerged, further facilitating their clinical application. In addition to cognitive training, regular physical exercise has been shown to markedly reduce the risk of delirium (166–168). This protective effect is potentially mediated by mechanisms such as increased skeletal muscle mass, elevated BDNF levels, enhanced angiogenesis and improved cerebral blood flow. Sleep regulation is another key component of POD prevention. Non-pharmacological strategies to improve sleep quality, such as using earplugs and eye masks, dimming lights and reducing nighttime nursing activities, have been demonstrated to decrease both the incidence and severity of POD (169,170). Similarly, multisensory stimulation, including music therapy, olfactory training and environmental enrichment, has been revealed to reduce the risk of POD in elderly patients (69,171–173),. Multicomponent interventions, such as Hospital Elder Life Program (HELP), are regarded as the most effective strategy for delirium prevention (174–176). A meta-analysis involving 3,605 patients with delirium demonstrated that HELP-based interventions reduce the likelihood of delirium by 53% (177). Additionally, several other approaches have demonstrated efficacy in preventing and managing POD. These include transcutaneous acupoint electrical stimulation, non-invasive brain stimulation, comprehensive geriatric assessment and delirium-specialized hospital units (178). These interventions provide diverse strategies for addressing POD and may contribute to improved patient outcomes (Table I).
At present, the prevention of POD in China primarily relies on pharmacological interventions; however, reliable supporting evidence remains limited (179–194). Previous studies have suggested that antipsychotic drugs are the first-line treatment for POD due to their sedative, antiemetic, anxiolytic and sleep-improving properties, but they may also lead to considerable extrapyramidal side effects (179–181). The role of benzodiazepines in POD has been debated. While they were once considered an independent risk factor, recent studies have revealed no clear association between benzodiazepine use and increased POD risk (182,183). Moreover, some short-acting benzodiazepines, such as remimazolam and midazolam, may even reduce the incidence of POD (184). Dexmedetomidine is a first-line agent for preventing POD and ICU delirium, offering sedative, analgesic, anxiolytic, sympatholytic and cardiovascular stabilizing effects (185–187). Additionally, randomized controlled trials (RCTs) have demonstrated the potential benefits of esketamine (188–190), melatonin (191,192), NSAIDs (193,194) and glucocorticoids (195,196) in improving POD outcomes. In recent years, intranasal insulin administration has emerged as a potential strategy for reducing POD incidence (56,197). However, the effects of pharmacological interventions on POD remain controversial. A standardized protocol for drug timing and dosage has yet to be established, necessitating further validation through multicenter, large-sample, high-quality clinical trials (Table II).
Anesthesia and surgery serve a key role in the development of POD, and appropriate perioperative anesthesia management can help mitigate this risk (198–209). Regional blockade combined with general anesthesia has been shown to attenuate endocrine and surgical stress responses, reduce opioid consumption and improve postoperative pain control, making it an effective strategy for POD prevention (198–200). Maintaining an optimal depth of anesthesia through intraoperative EEG and bispectral index monitoring can help prevent burst suppression and minimize anesthetic exposure, thereby potentially reducing the incidence of POD (83,201). Additionally, adopting lung-protective ventilation strategies (202,203), optimizing blood pressure regulation (204,205) and monitoring regional cerebral oxygen saturation (206) can enhance cerebral blood flow, improve brain perfusion and ensure adequate oxygenation, further lowering the risk of POD. Other effective perioperative anesthesia management strategies for POD prevention include temperature monitoring, multimodal analgesia and goal-directed fluid therapy (207–209). However, current research on anesthesia management remains largely focused on single-modality interventions. There is an urgent need to explore comprehensive, multimodal approaches and to develop standardized clinical anesthesia management pathways to optimize POD prevention and patient outcomes (Table III).
Limitations
The present review has several limitations. First, it primarily focuses on studies published in the English language, with data limited to a specific academic database. While this database is comprehensive, it may have overlooked relevant studies published in other languages or those not included in the searched database. Second, due to limited data on some interventions, the present review includes several retrospective studies, which may be subject to recall bias and other confounding factors. Additionally, some interventions showed contradictory results, and more large-scale RCTs with standardized methods may be needed for further validation. Another limitation is that the studies included in the present review focus on specific populations, which may limit the applicability of the findings to other patient groups. Moreover, different studies employed various diagnostic criteria and assessment methods, which could impact the consistency and reliability of the results.
Summary
With the widespread adoption of enhanced recovery after surgery protocols and the growing demand for perioperative comfort care, there has been increasing attention on postoperative complications. POD is one of the most common and concerning complications, but its pathogenesis remains unclear, and effective preventive and therapeutic strategies are still lacking. The present review provides a comprehensive and innovative analysis of the mechanisms underlying POD, including the associated signaling pathways, while summarizing preventive and therapeutic strategies across three key areas: Pharmacological interventions, non-pharmacological interventions and anesthesia management.
However, several key issues need to be addressed in future research. First, robust preclinical models are needed to effectively replicate human postoperative POD conditions, enabling further exploration of the mechanisms that trigger POD and its downstream effects. Understanding how various interventions influence these processes is essential for developing more targeted and effective treatments. Second, standardized inclusion criteria and diagnostic methods must be established to enhance the comparability of therapeutic efficacy and ensure the consistency and reliability of research findings. Furthermore, the potential role of neuroimaging and biomarkers in diagnosing POD should be thoroughly investigated. Third, although some interventions have demonstrated promising results, controversies remain regarding their effectiveness. To resolve these uncertainties, large-scale, multicenter RCTs are required to validate their efficacy. Additionally, clinical practice should integrate multimodal interventions that combine pharmacological treatments with non-pharmacological approaches, rather than focusing exclusively on pharmacological interventions or single-treatment strategies. In summary, closing these research gaps will enhance the understanding of POD and facilitate the development of more effective strategies for its prevention and management.
Acknowledgements
Not applicable.
Funding
The present review was funded by the Major Project of the General Hospital of Western Theater Command (grant no. 2021-XZYG-A10), the Youth Incubation Project of the General Hospital of Western Theater Command (grant no. 2021-XZYG-C25) and the Clinical Independent Innovation Project of the General Hospital of Western Theater Command (grant no. 2024-YGLC-B12).
Availability of data and materials
Not applicable.
Authors' contributions
WQL designed the study and wrote the manuscript. QS and JZZ created the figures using BioRender (https://www.biorender.com/). RHB, LL and XMD conducted the literature search. QQH and GG revised the manuscript. All authors read and approved the final version of the manuscript. Data authentication is not applicable.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
|
Feng H, Zhang Z, Lyu W, Kong X, Li J, Zhou H and Wei P: The effects of appropriate perioperative exercise on perioperative neurocognitive disorders: A narrative review. Mol Neurobiol. 61:4663–4676. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Tang X, Li J, Yang B, Lei C and Dong H: Efficacy of sleep interventions on postoperative delirium: A systematic review and meta-analysis of randomiszed controlled trials. APS. 1:292023. View Article : Google Scholar | |
|
Ishizawa Y: Preoperative cognitive optimization and postoperative cognitive outcomes: A narrative review. Clin Interv Aging. 20:395–402. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Chen M, Liang H, Zhao Y, Liao R, Fang J, Lin L, Tan P, Xu Y, Chen S, Chen H and Wei L: The perioperative frailty index derived from the Chinese hospital information system: A validation study. BMC Geriatr. 24:9572024. View Article : Google Scholar : PubMed/NCBI | |
|
Dilmen OK, Meco BC, Evered LA and Radtke FM: Postoperative neurocognitive disorders: A clinical guide. J Clin Anesth. 92:1113202024. View Article : Google Scholar : PubMed/NCBI | |
|
Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, Oh ES, Crosby G, Berger M and Eckenhoff RG; Nomenclature Consensus Working Group, : Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth. 121:1005–1012. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chinese Society of Geriatric Medicine and Anesthesiology Branch, . Expert Consensus on the Prevention and Treatment of Postoperative Delirium in Elderly Patients. International Journal of Anesthesia and Resuscitation. 44:1–27. 2023. | |
|
Hughes CG, Boncyk CS, Culley DJ, Fleisher LA, Leung JM, McDonagh DL, Gan TJ, McEvoy MD and Miller TE; Perioperative Quality Initiative (POQI) 6 Workgroup, : American society for enhanced recovery and perioperative quality initiative joint consensus statement on postoperative delirium prevention. Anesth Analg. 130:1572–1590. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard GR and Inouye SK: Evaluation of delirium in critically ill patients: Validation of the confusion assessment method for the intensive care unit (CAM-ICU). Crit Care Med. 29:1370–1379. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Gaudreau JD, Gagnon P, Harel F, Tremblay A and Roy MA: Fast, systematic, and continuous delirium assessment in hospitalized patients: The nursing delirium screening scale. J Pain Symptom Manage. 29:368–375. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Hargrave A, Bastiaens J, Bourgeois JA, Neuhaus J, Josephson SA, Chinn J, Lee M, Leung J and Douglas V: Validation of a nurse-based delirium-screening tool for hospitalized patients. Psychosomatics. 58:594–603. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Neufeld KJ, Leoutsakos JS, Sieber FE, Joshi D, Wanamaker BL, Rios-Robles J and Needham DM: Evaluation of two delirium screening tools for detecting post-operative delirium in the elderly. Br J Anaesth. 111:612–618. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Gusmao-Flores D, Salluh JIF, Chalhub RÁ and Quarantini LC: The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: A systematic review and meta-analysis of clinical studies. Crit Care. 16:R1152012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang L, Qiu Y, Zhang Z, Zhao Y and Ding Y: Current perspectives on postoperative cognitive dysfunction in geriatric patients: Insights from clinical practice. Front Med (Lausanne). 11:14666812024. View Article : Google Scholar : PubMed/NCBI | |
|
Sprung J, Roberts RO, Weingarten TN, Cavalcante AN, Knopman DS, Petersen RC, Hanson AC, Schroeder DR and Warner DO: Postoperative delirium in elderly patients is associated with subsequent cognitive impairment. Br J Anaesth. 119:316–323. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Goldberg TE, Chen C, Wang Y, Jung E, Swanson A, Ing C, Garcia PS, Whittington RA and Moitra V: Association of delirium with long-term cognitive decline: A meta-analysis. JAMA Neurol. 77:1373–1381. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Kunicki ZJ, Ngo LH, Marcantonio ER, Tommet D, Feng Y, Fong TG, Schmitt EM, Travison TG, Jones RN and Inouye SK: Six-year cognitive trajectory in older adults following major surgery and delirium. JAMA Intern Med. 183:442–450. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Glumac S, Kardum G and Karanovic N: Postoperative cognitive decline after cardiac surgery: A narrative review of current knowledge in 2019. Med Sci Monit. 25:3262–3270. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Yang AC, Stevens MY, Chen MB, Lee DP, Stähli D, Gate D, Contrepois K, Chen W, Iram T, Zhang L, et al: Physiological blood-brain transport is impaired with age by a shift in transcytosis. Nature. 583:425–430. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Subramaniyan S and Terrando N: Neuroinflammation and perioperative neurocognitive disorders. Anesth Analg. 128:781–788. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Lin X, Tang J, Liu C, Li X, Cao X, Wang B, Dong R, Xu W, Yu X, Wang M and Bi Y: Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing total hip/knee replacement: A prospective cohort study. BMC Anesthesiol. 20:2462020. View Article : Google Scholar : PubMed/NCBI | |
|
Lu J, Liang F, Bai P, Liu C, Xu M, Sun Z, Tian W, Dong Y, Zhang Y, Quan Q, et al: Blood tau-PT217 contributes to the anesthesia/surgery-induced delirium-like behavior in aged mice. Alzheimers Dement. 19:4110–4126. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J and Wesselingh S: From gut dysbiosis to altered brain function and mental illness: Mechanisms and pathways. Mol Psychiatry. 21:738–748. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang C, Han Y, Liu X, Tan H, Dong Y, Zhang Y, Liang F, Zheng H, Crosby G, Culley DJ, et al: Odor enrichment attenuates the anesthesia/surgery-induced cognitive impairment. Ann Surg. 277:e1387–e1396. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Vance DE, Del Bene VA, Kamath V, Frank JS, Billings R, Cho DY, Byun JY, Jacob A, Anderson JN, Visscher K, et al: Does olfactory training improve brain function and cognition? A systematic review. Neuropsychol Rev. 34:1–37. 2023. | |
|
Nogueira-de-Almeida CA, Zotarelli-Filho IJ, Nogueirade-Almeida ME, Souza CG, Kemp VL and Ramos WS: Neuronutrients and central nervous system: A systematic review. Cent Nerv Syst Agents Med Chem. 23:1–12. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Kashyap B, Hanson LR and Frey II WH: Intranasal insulin: a treatment strategy for addiction. Neurotherapeutics. 17:105–115. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Caplan GA, Kvelde T, Lai C, Yap SL, Lin C and Hill MA: Cerebrospinal fluid in long-lasting delirium compared with alzheimer's dementia. J Gerontol A Biol Sci Med Sci. 65:1130–1136. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Safar ME: Arterial aging-hemodynamic changes and therapeutic options. Nat Rev Cardiol. 7:442–449. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Huang QQ, Lei N, Li SN, Wei Y, Yuan LB and Gong G: Progress in intranasal insulin administration and postoperative delirium. J Clin Anesthesiol. 38:101–104. 2022. | |
|
Yokota H, Ogawa S, Kurokawa A and Yamamoto Y: Regional cerebral blood flow in delirium patients. Psychiatry Clin Neurosci. 57:337–339. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Akintola AA, van Opstal AM, Westendorp RG, Postmus I, van der Grond J and van Heemst D: Effect of intranasally administered insulin on cerebral blood flow and perfusion; a randomized experiment in young and older adults. Aging (Albany NY). 9:790–802. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Oh TK and Song IA: Preoperative cognitive function and surgical outcomes under general anesthesia among older patients. J Clin Anesth. 104:1118522025. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang Y, Fang P, Shang Z, Zhu W, Gao S and Liu X: Cognitive training in surgical patients: A systematic review and meta-analysis. APS. 1:182023. View Article : Google Scholar : PubMed/NCBI | |
|
Qiu X, Wang L, Wen X, Meng Q, Qi J, Li C, Yin H, Ling F, Yuhan Q, Zhang W and Zhang Y: Effect of different durations of preoperative computerised cognitive training on postoperative delirium in older patients undergoing cardiac surgery: A study protocol for a prospective, randomised controlled trial. BMJ Open. 14:e0881632024. View Article : Google Scholar : PubMed/NCBI | |
|
Alam A, Hana Z, Jin Z, Suen KC and Ma D: Surgery, neuroinflammation and cognitive impairment. EBioMedicine. 37:547–556. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Brabazon F, Bermudez S, Shaughness M, Khayrullina G and Byrnes KR: The effects of insulin on the inflammatory activity of BV2 microglia. PLoS One. 13:e02018782018. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Wang D, Yin K, Liu Y, Lu H, Zhao H and Xing M: Lycopene attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/NF-B balance in sulfamethoxazole-induced neurotoxicity in grass carp (ctenopharyngodon idella). Fish Shellfish Immunol. 121:322–331. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Lu H, Guo T, Zhang Y, Liu D, Hou L, Ma C and Xing M: Endoplasmic reticulum stress-induced NLRP3 inflammasome activation as a novel mechanism of polystyrene microplastics (PS-MPs)-induced pulmonary inflammation in chickens. J Zhejiang Univ Sci B. 25:233–243. 2024.(In English, Chinese). View Article : Google Scholar : PubMed/NCBI | |
|
Sabolová G, Kočan L, Rabajdová M, Rapčanová S and Vašková J: Association of inflammation, oxidative stress, and deteriorated cognitive functions in patients after cardiac surgery. Vessel Plus. 8:272024. | |
|
Glumac S, Kardum G, Sodic L, Supe-Domic D and Karanovic N: Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial. Eur J Anaesthesiol. 34:776–784. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Sinsky J, Pichlerova K and Hanes J: Tau protein interaction partners and their roles in Alzheimer's disease and other tauopathies. Int J Mol Sci. 22:92072021. View Article : Google Scholar : PubMed/NCBI | |
|
Tao G, Zhang J, Zhang L, Dong Y, Yu B, Crosby G, Culley DJ, Zhang Y and Xie Z: Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3 activation in young mice. Anesthesiology. 121:510–527. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Whittington RA, Bretteville A, Dickler MF and Planel E: Anesthesia and tau pathology. Prog Neuropsychopharmacol Biol Psychiatry. 47:147–155. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Tu S, Okamoto S, Lipton SA and Xu H: Oligomeric a-induced synaptic dysfunction in Alzheimer's disease. Mol Neurodegener. 9:482014. View Article : Google Scholar : PubMed/NCBI | |
|
Liu C, Zhang C, Chen L, Liu X, Wu J, Sun Y, Liu J and Chen C: Lingo1 in the hippocampus contributes to cognitive dysfunction after anesthesia and surgery in aged mice. Int J Biol Sci. 21:595–613. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Peng L, Fang X, Xu F, Liu S, Qian Y, Gong X, Zhao X, Ma Z, Xia T and Gu X: Amelioration of hippocampal insulin resistance reduces tau hyperphosphorylation and cognitive decline induced by isoflurane in mice. Front Aging Neurosci. 13:6865062021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu J, Li C, Yao J, Zhang L, Zhao X, Lv X, Liu Z, Miao C, Wang Y, Jiang H, et al: Clinical biomarkers of perioperative neurocognitive disorder: Initiation and recommendation. Sci China Life Sci. 22:10.1007/s11427–024-2797-x. 2025. | |
|
Wang S, Greene R, Song Y, Chan C, Lindroth H, Khan S, Rios G, Sanders RD and Khan B: Postoperative delirium and its relationship with biomarkers for dementia: A meta-analysis. Int Psychogeriatr. 34:377–390. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Fong TG, Vasunilashorn SM, Ngo L, Libermann TA, Dillon ST, Schmitt EM, Pascual-Leone A, Arnold SE, Jones RN, Marcantonio ER, et al: Association of plasma neurofilament light with postoperative delirium. Ann Neurol. 88:984–994. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lauretti E, Dincer O and Praticò D: Glycogen synthase kinase-3 signaling in Alzheimer's disease. Biochim Biophys Acta Mol Cell Res. 1867:1186642020. View Article : Google Scholar : PubMed/NCBI | |
|
Ahn EH and Park JB: Molecular mechanisms of Alzheimer's disease induced by amyloid- and tau phosphorylation along with RhoA activity: Perspective of RhoA/rho-associated protein kinase inhibitors for neuronal therapy. Cells. 14:892025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang H, Wei W, Zhao M, Ma L, Jiang X, Pei H, Cao Y and Li H: Interaction between A and Tau in the pathogenesis of Alzheimer's disease. Int J Biol Sci. 17:2181–2192. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Y, Zhang X, Jiang M, Zhang Y, Wang C, Sun Y, Shi Z and Wang B: Impact of preoperative sleep disturbances on postoperative delirium in patients with intracranial tumors: A prospective, observational, cohort study. Nat Sci Sleep. 15:1093–1105. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Guo H, Li LH, Lv XH, Su FZ, Chen J, Xiao F, Shi M and Xie YB: Association between preoperative sleep disturbance and postoperative delirium in elderly: A retrospective cohort study. Nat Sci Sleep. 16:389–400. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Huang Q, Wu X, Lei N, Chen X, Yu S, Dai X, Shi Q, Gong G and Shu HF: Effects of intranasal insulin pretreatment on preoperative sleep quality and postoperative delirium in patients undergoing valve replacement for rheumatic heart disease. Nat Sci Sleep. 16:613–623. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Telias I and Wilcox ME: Sleep and circadian rhythm in critical illness. Crit Care. 23:822019. View Article : Google Scholar : PubMed/NCBI | |
|
Lin Y, Xu S, Peng Y, Li S, Huang X and Chen L: Preoperative slow-wave sleep is associated with postoperative delirium after heart valve surgery: A prospective pilot study. J Sleep Res. 32:e139202023. View Article : Google Scholar : PubMed/NCBI | |
|
Dulko E, Jedrusiak M, Osuru HP, Atluri N, Illendula M, Davis EM, Beenhakker MP and Lunardi N: Sleep fragmentation, electroencephalographic slowing, and circadian disarray in a mouse model for intensive care unit delirium. Anesth Analg. 137:209–220. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Li S, Zhou H, Yu Y, Lyu H, Mou T, Shi G, Hu S, Huang M, Hu J and Xu Y: Effect of repetitive transcranial magnetic stimulation on the cognitive impairment induced by sleep deprivation: A randomized trial. Sleep Med. 77:270–278. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Sic A, Cvetkovic K, Manchanda E and Knezevic NN: Neurobiological implications of chronic stress and metabolic dysregulation in inflammatory bowel diseases. Diseases. 12:2202024. View Article : Google Scholar : PubMed/NCBI | |
|
Sugama S and Kakinuma Y: Stress and brain immunity: Microglial homeostasis through hypothalamus-pituitary-adrenal gland axis and sympathetic nervous system. Brain Behav Immun Health. 7:1001112020. View Article : Google Scholar : PubMed/NCBI | |
|
Sharan P and Vellapandian C: Hypothalamic-pituitary-adrenal (HPA) axis: Unveiling the potential mechanisms involved in stress-induced alzheimer's disease and depression. Cureus. 16:e675952024.PubMed/NCBI | |
|
Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR and Lewis LD: Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science. 366:628–631. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Figueroa-Ramos MI, Arroyo-Novoa CM, Lee KA, Padilla G and Puntillo KA: Sleep and delirium in ICU patients: A review of mechanisms and manifestations. Intensive Care Med. 35:781–795. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Han SA, Kim JK, Cho DY, Patel ZM and Rhee CS: The olfactory system: Basic anatomy and physiology for general otorhinolaryngologists. Clin Exp Otorhinolaryngol. 16:308–316. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Marin C, Vilas D, Langdon C, Alobid I, López-Chacón M, Haehner A, Hummel T and Mullol J: Olfactory dysfunction in neurodegenerative diseases. Curr Allergy Asthma Rep. 18:422018. View Article : Google Scholar : PubMed/NCBI | |
|
Kamath V, Yanek LR, Neufeld KJ, Lewis A, Aziz H, Le LM, Tian J, Moghekar A, Hogue CW Jr and Brown CH IV: Poor olfaction prior to cardiac surgery: Association with cognition, plasma neurofilament light, and post-operative delirium. Int J Geriatr Psychiatry. 39:e60662024. View Article : Google Scholar : PubMed/NCBI | |
|
Yang Y, Chen J, Wen Q, Jin G, Liu F, Yu L and He J: Effects of preoperative neoadjuvant chemotherapy on postoperative delirium in patients with gynecological tumor surgery: An observational study. J Cancer Res Clin Oncol. 150:4972024. View Article : Google Scholar : PubMed/NCBI | |
|
Liang H and Wang HR: Research progress on the correlation between olfactory disorders and cognitive impairment based on the olfactory-brain connection pathway. Liaoning J Tradit Chin Med. 52:199–202. 2025.(In Chinese). | |
|
Pasquini J, Brooks DJ and Pavese N: The cholinergic brain in Parkinson's disease. Mov Disord Clin Pract. 8:1012–1026. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Gao Q, Sun TP and Wu GY: Research progress on the pathophysiological mechanisms of postoperative delirium in elderly patients. Med Res Educ. 39:8–13. 2022. | |
|
Mayer EA, Tillisch K and Gupta A: Gut/brain axis and the microbiota. J Clin Invest. 125:926–938. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Chen Y, Xu J and Chen Y: Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders. Nutrients. 13:20992021. View Article : Google Scholar : PubMed/NCBI | |
|
Liufu N, Liu L, Shen S, Jiang Z, Dong Y, Wang Y, Culley D, Crosby G, Cao M, Shen Y, et al: Anesthesia and surgery induce age-dependent changes in behaviors and microbiota. Aging (Albany NY). 12:1965–1986. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lu J, Hou W, Gao S, Zhang Y and Zong Y: The role of gut microbiota-gut-brain axis in perioperative neurocognitive dysfunction. Front Pharmacol. 13:8797452022. View Article : Google Scholar : PubMed/NCBI | |
|
Qu S, Yu Z, Zhou Y, Wang S, Jia M, Chen T and Zhang X: Gut microbiota modulates neurotransmitter and gut-brain signaling. Microbiol Res. 287:1278582024. View Article : Google Scholar : PubMed/NCBI | |
|
Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG and Cowan CSM: The gut microbiota in anxiety and depression-a systematic review. Clin Psychol Rev. 83:1019432021. View Article : Google Scholar : PubMed/NCBI | |
|
Kolobaric A, Andreescu C, Jašarević E, Hong CH, Roh HW, Cheong JY, Kim YK, Shin TS, Kang CS, Kwon CO, et al: Gut microbiome predicts cognitive function and depressive symptoms in late life. Mol Psychiatry. 29:3064–3075. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Ma K and Bebawy JF: Electroencephalographic burst-suppression, perioperative neuroprotection, postoperative cognitive function, and mortality: A focused narrative review of the literature. Anesth Analg. 135:79–90. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Chen YC, Hung IY, Hung KC, Chang YJ, Chu CC, Chen JY, Ho CH and Yu CH: Incidence change of postoperative delirium after implementation of processed electroencephalography monitoring during surgery: A retrospective evaluation study. BMC Anesthesiol. 23:3302023. View Article : Google Scholar : PubMed/NCBI | |
|
Al-Qudah AM, Sivaguru S, Anetakis K, Crammond DJ, Balzer JR, Thirumala PD, Subramaniam K, Sadhasivam S and Shandal V: Role of intraoperative electroencephalography in predicting postoperative delirium in patients undergoing cardiovascular surgeries. Clin Neurophysiol. 164:40–46. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Evered LA, Chan MTV, Han R, Chu MHM, Cheng BP, Scott DA, Pryor KO, Sessler DI, Veselis R, Frampton C, et al: Anaesthetic depth and delirium after major surgery: A randomised clinical trial. Br J Anaesth. 127:704–712. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Lele AV, Furman M, Myers J, Kinney G, Sharma D and Hecker J: Inadvertent burst suppression during total intravenous anesthesia in 112 consecutive patients undergoing spinal instrumentation surgery: A retrospective observational quality improvement project. J Neurosurg Anesthesiol. 34:300–305. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Li RX, Jiang ZS and Gu WD: Research progress on burst suppression during general anesthesia and perioperative neurocognitive dysfunction. Geriatr Med Health Care. 29:833–836. 2023. | |
|
Vasunilashorn SM, Ngo LH, Inouye SK, Fong TG, Jones RN, Dillon ST, Libermann TA, O'Connor M, Arnold SE, Xie Z and Marcantonio ER: Apolipoprotein E genotype and the association between C-reactive protein and postoperative delirium: Importance of gene-protein interactions. Alzheimers Dement. 16:572–580. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Sepulveda E, Adamis D, Franco JG, Meagher D, Aranda S and Vilella E: The complex interaction of genetics and delirium: A systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 271:929–939. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
van Munster BC, Yazdanpanah M, Tanck MWT, de Rooij SE, van de Giessen E, Sijbrands EJ, Zwinderman AH and Korevaar JC: Genetic polymorphisms in the DRD2, DRD3, and SLC6A3 gene in elderly patients with delirium. Am J Med Genet B Neuropsychiatr Genet. 153B:38–45. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Wang SQ and Cao J: Research progress on postoperative delirium in elderly orthopedic patients. Chongqing Med. 52:3182–3187. 2023.(In Chinese). | |
|
Zhang M and Yin Y: Dual roles of anesthetics in postoperative cognitive dysfunction: Regulation of microglial activation through inflammatory signaling pathways. Front Immunol. 14:11023122023. View Article : Google Scholar : PubMed/NCBI | |
|
Chae WJ and Bothwell ALM: Canonical and non-canonical wnt signaling in immune cells. Trends Immunol. 39:830–847. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chang X, Yang WQ, Han CF, Zhao XL and Chen Y: Mechanism of the Wnt/-catenin signaling pathway in sevoflurane-induced postoperative cognitive dysfunction. J Integr Tradit Chin West Med Cardiovasc Dis. 22:75–78. 2024.(In Chinese). | |
|
Hu N, Wang C, Zheng Y, Ao J, Zhang C, Xie K, Li Y, Wang H, Yu Y and Wang G: The role of the wnt/-catenin-annexin A1 pathway in the process of sevoflurane-induced cognitive dysfunction. J Neurochem. 137:240–252. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Killick R, Ribe EM, Al-Shawi R, Malik B, Hooper C, Fernandes C, Dobson R, Nolan PM, Lourdusamy A, Furney S, et al: Clusterin regulates -amyloid toxicity via dickkopf-1-driven induction of the wnt-PCP-JNK pathway. Mol Psychiatry. 19:88–98. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Lu H, Yin K, Su H, Wang D, Zhang Y, Hou L, Li JB, Wang Y and Xing M: Polystyrene microplastics induce autophagy and apoptosis in birds lungs via PTEN/PI3K/AKT/mTOR. Environ Toxicol. 38:78–89. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Zeng GH, Zhu T, Zou L and Zhou J: Research progress on the PI3K/Akt-related signaling pathway in the pathophysiological mechanisms of neural cells. Chin J Pathophysiol. 40:1529–1535. 2024.(In Chinese). | |
|
Ochalek A, Mihalik B, Avci HX, Chandrasekaran A, Téglási A, Bock I, Giudice ML, Táncos Z, Molnár K, László L, et al: Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation. Alzheimers Res Ther. 9:902017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Q, Li S, Li M, Ke D, Wang Q, Yang Y, Liu GP, Wang XC, Liu E and Wang JZ: Human tau accumulation promotes glycogen synthase kinase-3 acetylation and thus upregulates the kinase: A vicious cycle in Alzheimer neurodegeneration. EBioMedicine. 78:1039702022. View Article : Google Scholar : PubMed/NCBI | |
|
Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, et al: Lithium trial in Alzheimer's disease: A randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry. 70:922–931. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Yamamoto N, Ishikuro R, Tanida M, Suzuki K, Ikeda-Matsuo Y and Sobue K: Insulin-signaling pathway regulates the degradation of amyloid-protein via astrocytes. Neuroscience. 385:227–236. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Rekha A, Afzal M, Babu MA, Menon SV, Nathiya D, Supriya S, Mishra SB, Gupta S, Goyal K, Rana M, et al: GSK-3 dysregulation in aging: Implications for tau pathology and Alzheimer's disease progression. Mol Cell Neurosci. 133:1040052025. View Article : Google Scholar : PubMed/NCBI | |
|
Jolivalt CG, Lee CA, Beiswenger KK, Smith JL, Orlov M, Torrance MA and Masliah E: Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: Parallels with Alzheimer's disease and correction by insulin. J Neurosci Res. 86:3265–3274. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Llorens-Martín M, Jurado J, Hernández F and Avila J: GSK-3, a pivotal kinase in alzheimer disease. Front Mol Neurosci. 7:462014.PubMed/NCBI | |
|
Gianferrara T, Cescon E, Grieco I, Spalluto G and Federico S: Glycogen synthase kinase 3 involvement in neuroinflammation and neurodegenerative diseases. Curr Med Chem. 29:4631–4697. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Guo M, Wang Y, Zhao H, Wang D, Yin K, Liu Y, Li B and Xing M: Zinc antagonizes common carp (cyprinus carpio) intestinal arsenic poisoning through PI3K/AKT/mTOR signaling cascade and MAPK pathway. Aquat Toxicol. 240:1059862021. View Article : Google Scholar : PubMed/NCBI | |
|
Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J and Pedraza-Chaverri J: The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 26:2694–2701. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Gao S, Zhang S, Zhou H, Tao X, Ni Y, Pei D, Kang S, Yan W and Lu J: Role of mTOR-regulated autophagy in synaptic plasticity related proteins downregulation and the reference memory deficits induced by anesthesia/surgery in aged mice. Front Aging Neurosci. 13:6285412021. View Article : Google Scholar : PubMed/NCBI | |
|
Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, Eng H, Nair MG, Makvandi P, Geoerger B, et al: PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 22:1382023. View Article : Google Scholar : PubMed/NCBI | |
|
Chen M, Han Y, Que B, Zhou R, Gan J and Dong X: Prophylactic effects of sub-anesthesia ketamine on cognitive decline, neuroinflammation, and oxidative stress in elderly mice. Am J Alzheimers Dis Other Demen. 37:153331752211415312022. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng LL, Tian Y, Tan YW and Wang D: Effect of dexmedetomidine on hippocampal neuronal autophagy in rats with postoperative neurocognitive dysfunction after hepatectomy via the PI3K/Akt/mTOR signaling pathway. West Med. 33:793–798. 8032021. | |
|
Brasil FB, Gobbo RC, de Almeida FJ, Luckachaki MD, Dall'Oglio EL and de Oliveira MR: The signaling pathway PI3K/Akt/Nrf2/HO-1 plays a role in the mitochondrial protection promoted by astaxanthin in the SH-SY5Y cells exposed to hydrogen peroxide. Neurochem Int. 146:1050242021. View Article : Google Scholar : PubMed/NCBI | |
|
Deng Q, Liang JQ, Gao CH, Ge X, Zheng JJ and Zhang QP: Effects of electroacupuncture on the PI3K/Akt/CREB signaling pathway and hippocampal neuronal apoptosis in diabetic cognitive impairment rats. Zhen Ci Yan Jiu. 49:265–273. 2024.(In English, Chinese). PubMed/NCBI | |
|
Ma RJ, Kannan M, Xia Q, Zhang SS, Tu PF, Liu KC and Zhang Y: Kunxian capsule extract inhibits angiogenesis in zebrafish embryos via PI3K/AKT-MAPK-VEGF pathway. Chin J Integr Med. 29:137–145. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Yang YR: Role and mechanism of the BDNF/TrkB signaling pathway in sevoflurane-induced cognitive dysfunction in aged rats. Inner Mongolia Medical University; 2022 | |
|
Qiu LL, Ji MH, Zhang H and Yang JJ, Sun XR, Tang H, Wang J, Liu WX and Yang JJ: NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice. Brain Behav Immun. 51:109–118. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Qiu LL, Pan W, Luo D, Zhang GF, Zhou ZQ, Sun XY, Yang JJ and Ji MH: Dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca2+/calpain might contribute to postoperative cognitive dysfunction in aging mice. J Neuroinflammation. 17:232020. View Article : Google Scholar : PubMed/NCBI | |
|
Jia J, Zhu J, Yang Q, Wang Y, Zhang Z and Chen C: The role of histone acetylation in the sevoflurane-induced inhibition of neurogenesis in the hippocampi of young mice. Neuroscience. 432:73–83. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Fan D, Li J, Zheng B, Hua L and Zuo Z: Enriched environment attenuates surgery-induced impairment of learning, memory, and neurogenesis possibly by preserving BDNF expression. Mol Neurobiol. 53:344–354. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Pisani A, Paciello F, Del Vecchio V, Malesci R, De Corso E, Cantone E and Fetoni AR: The role of BDNF as a biomarker in cognitive and sensory neurodegeneration. J Pers Med. 13:6522023. View Article : Google Scholar : PubMed/NCBI | |
|
Gao L, Zhang Y, Sterling K and Song W: Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential. Transl Neurodegener. 11:42022. View Article : Google Scholar : PubMed/NCBI | |
|
Jiao SS, Shen LL, Zhu C, Bu XL, Liu YH, Liu CH, Yao XQ, Zhang LL, Zhou HD, Walker DG, et al: Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease. Transl Psychiatry. 6:e9072016. View Article : Google Scholar : PubMed/NCBI | |
|
Wu L, Xian X, Xu G, Tan Z, Dong F, Zhang M and Zhang F: Toll-like receptor 4: A promising therapeutic target for Alzheimer's disease. Mediators Inflamm. 2022:79241992022. View Article : Google Scholar : PubMed/NCBI | |
|
Duan T, Du Y, Xing C, Wang HY and Wang RF: Toll-like receptor signaling and its role in cell-mediated immunity. Front Immunol. 13:8127742022. View Article : Google Scholar : PubMed/NCBI | |
|
Lu SM, Yu CJ, Liu YH, Dong HQ, Zhang X, Zhang SS, Hu LQ, Zhang F, Qian YN and Gui B: S100A8 contributes to postoperative cognitive dysfunction in mice undergoing tibial fracture surgery by activating the TLR4/MyD88 pathway. Brain Behav Immun. 44:221–234. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, He H, Li D, Zhu W, Duan K, Le Y, Liao Y and Ou Y: The role of the TLR4 signaling pathway in cognitive deficits following surgery in aged rats. Mol Med Rep. 7:1137–1142. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Lin F, Shan W, Zheng Y, Pan L and Zuo Z: Toll-like receptor 2 activation and upregulation by high mobility group box l contribute to postoperative neuroinflammation and cognitive dysfunction in mice. J Neurochem. 158:328–341. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Yang C, Sun S, Zhang Q, Guo J, Wu T, Liu Y, Yang M, Zhang Y and Peng Y: Exosomes of antler mesenchymal stem cells improve postoperative cognitive dysfunction in cardiopulmonary bypass rats through inhibiting the TLR2/TLR4 signaling pathway. Stem Cells Int. 2020:21345652020. View Article : Google Scholar : PubMed/NCBI | |
|
Chen C, Gao R, Li M, Wang Q, Chen H, Zhang S, Mao X, Behensky A, Zhang Z, Gan L, et al: Extracellular RNAs-TLR3 signaling contributes to cognitive decline in a mouse model of postoperative cognitive dysfunction. Brain Behav Immun. 80:439–451. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Deng L, Gao R, Chen H, Jiao B, Zhang C, Wei L, Yan C, Ye-Lehmann S, Zhu T and Chen C: Let-7b-TLR7 signaling axis contributes to the anesthesia/surgery-induced cognitive impairment. Mol Neurobiol. 61:1818–1832. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Xie XY, Meng Y, Qiao ML, Wang YN and Yao WW: Research progress on traditional Chinese medicine intervention in Alzheimer's disease based on signaling pathways. Chin Med. 19:128–132. 2024.(In Chinese). PubMed/NCBI | |
|
Song H, Xun S, He H, Duan C and Li Q: Compound porcine cerebroside and ganglioside injection (CPCGI) attenuates sevoflurane-induced nerve cell injury by regulating the phosphorylation of p38 MAP kinase (p38MAPK)/nuclear factor kappa B (NF-B) pathway. Med Sci Monit. 26:e9196002020. View Article : Google Scholar : PubMed/NCBI | |
|
Lv JM, Gao YL, Wang LY, Li BD, Shan YL, Wu ZQ, Lu QM, Peng HY, Zhou TT, Li XM and Zhang LM: Inhibition of the P38 MAPK/NLRP3 pathway mitigates cognitive dysfunction and mood alterations in aged mice after abdominal surgery plus sevoflurane. Brain Res Bull. 217:1110592024. View Article : Google Scholar : PubMed/NCBI | |
|
Bikkavilli RK, Feigin ME and Malbon CC: p38 mitogen-activated protein kinase regulates canonical Wnt-catenin signaling by inactivation of GSK3. J Cell Sci. 121:3598–3607. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Chen Y, Li L, Zhang J, Cui H, Wang J, Wang C, Shi M and Fan H: Dexmedetomidine alleviates lipopolysaccharide-induced hippocampal neuronal apoptosis via inhibiting the p38 MAPK/c-myc/CLIC4 signaling pathway in rats. Mol Neurobiol. 58:5533–5547. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Sabapathy K: Role of the JNK pathway in human diseases. Prog Mol Biol Transl Sci. 106:145–169. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Rehfeldt SC, Majolo F, Goettert MI and Laufer S: c-Jun N-Terminal kinase inhibitors as potential leads for new therapeutics for Alzheimer's diseases. Int J Mol Sci. 21:96772020. View Article : Google Scholar | |
|
Li Y, Wang F, Liu C, Zeng M, Han X, Luo T, Jiang W, Xu J and Wang H: JNK pathway may be involved in isoflurane-induced apoptosis in the hippocampi of neonatal rats. Neurosci Lett. 545:17–22. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bi C, Cai Q, Shan Y, Yang F, Sun S, Wu X and Liu H: Sevoflurane induces neurotoxicity in the developing rat hippocampus by upregulating connexin 43 via the JNK/c-Jun/AP-1 pathway. Biomed Pharmacother. 108:1469–1476. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Yang Z, Lv J, Li X, Meng Q, Yang Q, Ma W, Li Y and Ke ZJ: Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase-mediated damage of rat fetal neural stem cells. Sci Rep. 7:463042017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang LY, Tang ZJ and Han YZ: Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane-induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways. Mol Med Rep. 14:3403–3412. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao X, Li S, Gaur U and Zheng W: Artemisinin improved neuronal functions in alzheimer's disease animal model 3×tg mice and neuronal cells via stimulating the ERK/CREB signaling pathway. Aging Dis. 11:801–819. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Yufune S, Satoh Y, Akai R, Yoshinaga Y, Kobayashi Y, Endo S and Kazama T: Suppression of ERK phosphorylation through oxidative stress is involved in the mechanism underlying sevoflurane-induced toxicity in the developing brain. Sci Rep. 6:218592016. View Article : Google Scholar : PubMed/NCBI | |
|
Peng S, Yan HZ, Liu PR, Shi XW, Liu CL, Liu Q and Zhang Y: Phosphodiesterase 4 inhibitor roflumilast protects rat hippocampal neurons from sevoflurane induced injury via modulation of MEK/ERK signaling pathway. Cell Physiol Biochem. 45:2329–2337. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Straiko MMW, Young C, Cattano D, Creeley CE, Wang H, Smith DJ, Johnson SA, Li ES and Olney JW: Lithium protects against anesthesia-induced developmental neuroapoptosis. Anesthesiology. 110:862–868. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wang WY, Yang R, Hu SF, Wang H, Ma ZW and Lu Y: N-stearoyl-L-tyrosine ameliorates sevoflurane induced neuroapoptosis via MEK/ERK1/2 MAPK signaling pathway in the developing brain. Neurosci Lett. 541:167–172. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Huang H, Li Y, Wang X, Zhang Q, Zhao J and Wang Q: Electroacupuncture pretreatment protects against anesthesia/surgery-induced cognitive decline by activating CREB via the ERK/MAPK pathway in the hippocampal CA1 region in aged rats. Aging (Albany NY). 15:11227–11243. 2023.PubMed/NCBI | |
|
Sun Y, Liu WZ, Liu T, Feng X, Yang N and Zhou HF: Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 35:600–604. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Albert-Gascó H, Ros-Bernal F, Castillo-Gómez E and Olucha-Bordonau FE: MAP/ERK signaling in developing cognitive and emotional function and its effect on pathological and neurodegenerative processes. Int J Mol Sci. 21:44712020. View Article : Google Scholar : PubMed/NCBI | |
|
Huang X, Ying J, Yang D, Fang P, Wang X, Zhou B, Zhang L, Fang Y, Yu W, Liu X, et al: The mechanisms of sevoflurane-induced neuroinflammation. Front Aging Neurosci. 13:7177452021. View Article : Google Scholar : PubMed/NCBI | |
|
Yang D, Su J, Chen Y and Chen G: The NF-B pathway: Key players in neurocognitive functions and related disorders. Eur J Pharmacol. 984:1770382024. View Article : Google Scholar : PubMed/NCBI | |
|
Liu P, Gao Q, Guan L, Hu Y, Jiang J, Gao T, Sheng W, Xue X, Qiao H and Li T: Atorvastatin attenuates surgery-induced BBB disruption and cognitive impairment partly by suppressing NF-B pathway and NLRP3 inflammasome activation in aged mice. Acta Biochim Biophys Sin (Shanghai). 53:528–537. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Li ZQ, Rong XY, Liu YJ, Ni C, Tian XS, Mo N, Chui DH and Guo XY: Activation of the canonical nuclear factor-B pathway is involved in isoflurane-induced hippocampal interleukin-1 elevation and the resultant cognitive deficits in aged rats. Biochem Biophys Res Commun. 438:628–634. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Xin Y, Chu T, Liu C and Xu A: Dexmedetomidine attenuates perioperative neurocognitive disorders by suppressing hippocampal neuroinflammation and HMGB1/RAGE/NF-B signaling pathway. Biomed Pharmacother. 150:1130062022. View Article : Google Scholar : PubMed/NCBI | |
|
Dai J, Li X, Wang C, Gu S, Dai L, Zhang J, Fan Y and Wu J: Repeated neonatal sevoflurane induced neurocognitive impairment through NF-B-mediated pyroptosis. J Neuroinflammation. 18:1802021. View Article : Google Scholar : PubMed/NCBI | |
|
Tian Y, Guo S, Wu X, Ma L and Zhao X: Minocycline alleviates sevoflurane-induced cognitive impairment in aged rats. Cell Mol Neurobiol. 35:585–594. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Sun L, Yong Y, Wei P, Wang Y, Li H, Zhou Y, Ruan W, Li X and Song J: Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice. CNS Neurosci Ther. 28:390–400. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Zand H, Morshedzadeh N and Naghashian F: Signaling pathways linking inflammation to insulin resistance. Diabetes Metab Syndr. 11:S307–S309. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Fleming-de-Moraes CD, Rocha MR, Tessmann JW, de Araujo WM and Morgado-Diaz JA: Crosstalk between PI3K/Akt and Wnt/-catenin pathways promote colorectal cancer progression regardless of mutational status. Cancer Biol Ther. 23:1–13. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Muscat SM, Deems NP, Butler MJ, Scaria EA, Bettes MN, Cleary SP, Bockbrader RH, Maier SF and Barrientos RM: Selective TLR4 antagonism prevents and reverses morphine-induced persistent postoperative cognitive dysfunction, dysregulation of synaptic elements, and impaired BDNF signaling in aged male rats. J Neurosci. 43:155–172. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Guo Q, Jin Y, Chen X, Ye X, Shen X, Lin M, Zeng C, Zhou T and Zhang J: NF-B in biology and targeted therapy: New insights and translational implications. Signal Transduct Target Ther. 9:532024. View Article : Google Scholar : PubMed/NCBI | |
|
Rubin FH, Neal K, Fenlon K, Hassan S and Inouye SK: Sustainability and scalability of the hospital elder life program at a community hospital. J Am Geriatr Soc. 59:359–365. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults, . American geriatrics society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc. 63:142–150. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Humeidan ML, Reyes JPC, Mavarez-Martinez A, Roeth C, Nguyen CM, Sheridan E, Zuleta-Alarcon A, Otey A, Abdel-Rasoul M and Bergese SD: Effect of cognitive prehabilitation on the incidence of postoperative delirium among older adults undergoing major noncardiac surgery: The neurobics randomized clinical trial. JAMA Surg. 156:148–156. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang Y, Xie Y, Fang P, Shang Z, Chen L, Zhou J, Yang C, Zhu W, Hao X, Ding J, et al: Cognitive training for reduction of delirium in patients undergoing cardiac surgery: A randomized clinical trial. JAMA Netw Open. 7:e2473612024. View Article : Google Scholar : PubMed/NCBI | |
|
Saleh AJ, Tang GX, Hadi SM, Yan L, Chen MH, Duan KM, Tong J and Ouyang W: Preoperative cognitive intervention reduces cognitive dysfunction in elderly patients after gastrointestinal surgery: A randomized controlled trial. Med Sci Monit. 21:798–805. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Ogawa M, Izawa KP, Satomi-Kobayashi S, Kitamura A, Tsuboi Y, Komaki K, Ono R, Sakai Y, Tanaka H and Okita Y: Preoperative exercise capacity is associated with the prevalence of postoperative delirium in elective cardiac surgery. Aging Clin Exp Res. 30:27–34. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Yanagisawa T, Tatematsu N, Horiuchi M, Migitaka S, Yasuda S, Itatsu K, Kubota T and Sugiura H: Preoperative low physical activity is a predictor of postoperative delirium in patients with gastrointestinal cancer: A retrospective study. Asian Pac J Cancer Prev. 23:1753–1759. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Janssen TL, Steyerberg EW, Langenberg JCM, de Lepper CCHAVH, Wielders D, Seerden TCJ, de Lange DC, Wijsman JH, Ho GH, Gobardhan PD, et al: Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study. PLoS One. 14:e02181522019. View Article : Google Scholar : PubMed/NCBI | |
|
Shorofi SA, Dadashian P, Arbon P and Moosazadeh M: The efficacy of earplugs and eye masks for delirium severity and sleep quality in patients undergoing coronary artery bypass grafting in cardiac intensive care units: A single-blind, randomised controlled trial. Aust Crit Care. 37:74–83. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Kamdar BB, King LM, Collop NA, Sakamuri S, Colantuoni E, Neufeld KJ, Bienvenu OJ, Rowden AM, Touradji P, Brower RG and Needham DM: The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit Care Med. 41:800–809. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kappen PR, Mos MI, Jeekel J, Dirven CMF, Kushner SA, Osse RJ, Coesmans M, Poley MJ, van Schie MS, van der Holt B, et al: Music to prevent deliriUm during neuroSurgerY (MUSYC): A single-centre, prospective randomised controlled trial. BMJ Open. 13:e0699572023. View Article : Google Scholar : PubMed/NCBI | |
|
Han S, Cai Z, Cao L, Li J and Huang L: Effects of Chinese traditional five-element music intervention on postoperative delirium and sleep quality in elderly patients after non-cardiac surgery: A randomized controlled trial. Perioper Med (Lond). 13:472024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu F, Bai Y and Mo L: Effects of enriched environment on perioperative psychological status and cognitive function in patients with esophageal cancer. Chin J Mod Med. 28:96–100. 2018.(In Chinese). | |
|
Inouye SK, Bogardus ST, Charpentier PA, Leo-Summers L, Acampora D, Holford TR and Cooney LM Jr: multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 340:669–676. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Chen CCH, Li HC, Liang JT, Lai IR, Purnomo JDT, Yang YT, Lin BR, Huang J, Yang CY, Tien YW, et al: Effect of a modified hospital elder life program on delirium and length of hospital stay in patients undergoing abdominal surgery: A cluster randomized clinical trial. JAMA Surg. 152:827–834. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang YY, Yue JR, Xie DM, Carter P, Li QL, Gartaganis SL, Chen J and Inouye SK: Effect of the tailored, family-involved hospital elder life program on postoperative delirium and function in older adults: A randomized clinical trial. JAMA Intern Med. 180:17–25. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hshieh TT, Yang T, Gartaganis SL, Yue J and Inouye SK: Hospital elder life program: Systematic review and meta-analysis of effectiveness. Am J Geriatr Psychiatry. 26:1015–1033. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao L, Guo Y, Zhou X, Mao W, Zhu H, Chen L, Liu X, Zhang L, Xie Y and Li L: The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review. Front Neurol. 15:13698212024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE and Zhu SN: Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized controlled trial*. Crit Care Med. 40:731–739. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Hakim SM, Othman AI and Naoum DO: Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: A randomized trial. Anesthesiology. 116:987–997. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
van den Boogaard M, Slooter AJC, Brüggemann RJM, Schoonhoven L, Beishuizen A, Vermeijden JW, Pretorius D, de Koning J, Simons KS, Dennesen PJW, et al: Effect of haloperidol on survival among critically ill adults with a high risk of delirium. JAMA. 319:680–691. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Li H, Liu C, Yang Y, Wu QP, Xu JM, Wang DF, Sun JJ, Mao MM, Lou JS, Liu YH, et al: Effect of intraoperative midazolam on postoperative delirium in older surgical patients: A prospective, multicenter cohort study. Anesthesiology. 142:268–277. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Kim J, Lee S, Yoo BH, Lim YH and Jun IJ: The effects of remimazolam and inhalational anesthetics on the incidence of postoperative hyperactive delirium in geriatric patients undergoing hip or femur surgery under general anesthesia: A retrospective observational study. Medicina (Kaunas). 61:3362025. View Article : Google Scholar : PubMed/NCBI | |
|
Cai YH, Zhong JW, Ma HY, Szmuk P, Wang CY, Wang Z, Zhang XL, Dong LQ and Liu HC: Effect of remimazolam on emergence delirium in children undergoing laparoscopic surgery: A double-blinded randomized trial. Anesthesiology. 141:500–510. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Li S, Li R, Li M, Cui Q, Zhang X, Ma T, Wang D, Zeng M, Li H, Bao Z, et al: Dexmedetomidine administration during brain tumour resection for prevention of postoperative delirium: A randomised trial. Br J Anaesth. 130:e307–e316. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
van Norden J, Spies CD, Borchers F, Mertens M, Kurth J, Heidgen J, Pohrt A and Mueller A: The effect of peri-operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non-cardiac surgical patients: A randomised, double-blind placebo-controlled trial. Anaesthesia. 76:1342–1351. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M and Ma D: Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: A randomised, double-blind, placebo-controlled trial. Lancet. 388:1893–1902. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Liu J, Wang T, Song J and Cao L: Effect of esketamine on postoperative analgesia and postoperative delirium in elderly patients undergoing gastrointestinal surgery. BMC Anesthesiol. 24:462024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang CL, Yan Y, Zhang Y, Bai HL, Zhuang Q, Song NN, Feng CJ, Xie LJ, Wang SY, Li XH, et al: Effects of esketamine combined with dexmedetomidine on postoperative delirium and quality of recovery in elderly patients undergoing thoracoscopic radical lung cancer surgery: A randomized controlled trial. CNS Spectr. 20:1–10. 2024. | |
|
Xiong X, Shao Y, Chen D, Chen B, Lan X and Shi J: Effect of esketamine on postoperative delirium in patients undergoing cardiac valve replacement with cardiopulmonary bypass: A randomized controlled trial. Anesth Analg. 139:743–753. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Fazel MR, Mofidian S, Mahdian M, Akbari H and Razavizadeh MR: The effect of melatonin on prevention of postoperative delirium after lower limb fracture surgery in elderly patients: A randomized double blind clinical trial. Int J Burns Trauma. 12:161–167. 2022.PubMed/NCBI | |
|
Elbakry AEA, El-Desoky IM, Saafan AG and Elsersy HE: The impact of melatonin on postoperative delirium in geriatric patients after colorectal surgery: A randomized placebo-controlled trial. Minerva Anestesiol. 90:509–519. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang JH, Liu T, Bai Y, Chen YQ, Cui YH, Gao XY and Guo JR: The effect of parecoxib sodium on postoperative delirium in elderly patients with hip arthroplasty. Front Pharmacol. 14:9479822023. View Article : Google Scholar : PubMed/NCBI | |
|
Shen L, Chen J, Yang X, Hu J, Gao W, Chai X and Wang D: Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium. Front Psychiatry. 13:8896372022. View Article : Google Scholar : PubMed/NCBI | |
|
Huang JW, Yang YF, Gao XS and Xu ZH: A single preoperative low-dose dexamethasone may reduce the incidence and severity of postoperative delirium in the geriatric intertrochanteric fracture patients with internal fixation surgery: An exploratory analysis of a randomized, placebo-controlled trial. J Orthop Surg Res. 18:4412023. View Article : Google Scholar : PubMed/NCBI | |
|
Xiang XB, Chen H, Wu YL, Wang K, Yue X and Cheng XQ: The effect of preoperative methylprednisolone on postoperative delirium in older patients undergoing gastrointestinal surgery: A randomized, double-blind, placebo-controlled trial. J Gerontol A Biol Sci Med Sci. 77:517–523. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Huang Q, Shi Q, Yi X, Zeng J, Dai X, Lin L, Yang Y, Wu X and Gong G: Effect of repeated intranasal administration of different doses of insulin on postoperative delirium, serum and a protein in elderly patients undergoing radical esophageal cancer surgery. Neuropsychiatr Dis Treat. 19:1017–1026. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Choi HR, Kim S, Song IA and Oh TK: Anesthetic technique and incidence of delirium after total knee or hip arthroplasty: A nationwide cohort study. BMC Anesthesiol. 24:4332024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao L and Qiu D: Ultrasound-guided femoral nerve block reduced the incidence of postoperative delirium after total knee arthroplasty: A double-blind, randomized study. Medicine (Baltimore). 103:e405492024. View Article : Google Scholar : PubMed/NCBI | |
|
Lim EJ, Koh WU, Kim H, Kim HJ, Shon HC and Kim JW: Regional nerve block decreases the incidence of postoperative delirium in elderly hip fracture. J Clin Med. 10:35862021. View Article : Google Scholar : PubMed/NCBI | |
|
Radtke FM, Franck M, Lendner J, Krüger S, Wernecke KD and Spies CD: Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth. 110 (Suppl 1):i98–i105. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Zhu L, Li Y, Yin C, Hou Z and Wang Q: The potential role of lung-protective ventilation in preventing postoperative delirium in elderly patients undergoing prone spinal surgery: A preliminary study. Med Sci Monit. 26:e9265262020.PubMed/NCBI | |
|
Song J, Shao YM, Zhang GH, Fan BQ, Tao WH, Liu XF, Huang XC and Hu XW: Examining the impact of permissibility hypercapnia on postoperative delirium among elderly patients undergoing thoracoscopic-laparoscopic esophagectomy: A single-center investigative study. Shock. 62:319–326. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Xu X, Hu X, Wu Y, Li Y, Zhang Y, Zhang M and Yang Q: Effects of different BP management strategies on postoperative delirium in elderly patients undergoing hip replacement: A single center randomized controlled trial. J Clin Anesth. 62:1097302020. View Article : Google Scholar : PubMed/NCBI | |
|
Brown CH, Neufeld KJ, Tian J, Probert J, LaFlam A, Max L, Hori D, Nomura Y, Mandal K, Brady K, et al: Effect of targeting mean arterial pressure during cardiopulmonary bypass by monitoring cerebral autoregulation on postsurgical delirium among older patients: A nested randomized clinical trial. JAMA Surg. 154:819–826. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Wang JY, Li M, Wang P and Fang P: Goal-directed therapy based on rScO2 monitoring in elderly patients with one-lung ventilation: A randomized trial on perioperative inflammation and postoperative delirium. Trials. 23:6872022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang DD, Li Y, Hu XW, Zhang MC, Xu XM and Tang J: Comparison of restrictive fluid therapy with goal-directed fluid therapy for postoperative delirium in patients undergoing spine surgery: A randomized controlled trial. Perioper Med (Lond). 10:482021. View Article : Google Scholar : PubMed/NCBI | |
|
Wei W, Zheng X, Gu Y, Fu W, Tang C and Yao Y: Effect of general anesthesia with thoracic paravertebral block on postoperative delirium in elderly patients undergoing thoracoscopic lobectomy: A randomized-controlled trial. BMC Anesthesiol. 22:12022. View Article : Google Scholar : PubMed/NCBI | |
|
Mu DL, Zhang DZ, Wang DX, Wang G, Li CJ, Meng ZT, Li YW, Liu C and Li XY: Parecoxib supplementation to morphine analgesia decreases incidence of delirium in elderly patients after hip or knee replacement surgery: A randomized controlled trial. Anesth Analg. 124:1992–2000. 2017. View Article : Google Scholar : PubMed/NCBI |
