Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 115 - 115

Published: Jan. 7, 2025

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery quality of life. As the aging population grows, rising number patients has made PND an urgent clinical challenge. Despite increasing research efforts, pathophysiological mechanisms underlying remain inadequately characterized, underscoring need for more integrated framework to guide targeted interventions. To better understand molecular therapeutic targets PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches PubMed, Embase, Cochrane Library, Web Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, white matter lesions as central pathophysiology, with particular parallels encephalocele- sepsis-associated impairments. Among these, mediated pathways such NLRP3 inflammasome blood-brain barrier disruption, emerges pivotal driver, triggering cascades exacerbate neuronal injury. Oxidative stress synergistically amplify these effects, while imbalances alterations, including lesions, contribute synaptic decline. Anesthetic agents modulate interconnected pathways, exhibiting both protective detrimental effects. Propofol dexmedetomidine demonstrate neuroprotective properties suppressing neuroinflammation microglial activation, whereas inhalational anesthetics like sevoflurane intensify inflammatory responses. Ketamine, its anti-inflammatory potential, offers promise but requires further evaluation determine long-term safety efficacy. By bridging insights practice, highlights critical role personalized anesthetic strategies mitigating improving patients. It aims inform future decision-making address multifaceted

Language: Английский

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Blood-brain barrier disruption: a culprit of cognitive decline?

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 7, 2024

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also systemic diseases, which seriously influence the quality life and expectancy patients. As highly selective anatomical functional interface between circulation, blood-brain barrier (BBB) plays pivotal role in maintaining homeostasis normal function. The pathogenesis underlying cognitive may vary, nevertheless, accumulating evidences support BBB disruption as most prevalent contributing factor. This mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress excitotoxicity. However, direct evidence showing that causes is scarce, interestingly, manipulation opening alone exert beneficial or detrimental neurological effects. A overview present literature shows close relationship decline, risk factors disruption, well cellular molecular mechanisms disruption. Additionally, we discussed possible leading by potential therapeutic strategies prevent enhance repair. review aims foster more investigations on early diagnosis, effective therapeutics, rapid restoration against would yield better outcomes patients with dysregulated function, although their causative has yet been completely established.

Language: Английский

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Chronic Postsurgical Pain Raises Risk of Dementia

European Journal of Pain, Journal Year: 2025, Volume and Issue: 29(4)

Published: Feb. 21, 2025

ABSTRACT Purpose This study aimed to investigate the association between chronic postsurgical pain (CPSP) and risk of dementia, addressing a significant gap in existing literature highlighting potential implications for clinical practice public health. Patients Methods Utilising data from Taiwan's National Health Insurance Research Database, propensity score‐matched cohort was conducted involving 142,682 patients who underwent major surgery 2004 2018. CPSP defined as prolonged analgesic use post‐surgery, dementia diagnosis tracked until December 31, 2022. Multivariable Cox regression models were employed calculate adjusted hazard ratios (aHRs) versus non‐CPSP groups. Results Before score matching, ( n = 37,438) exhibited higher with aHRs 1.35 (95% CI: 1.30–1.40). After aHR remained elevated at 1.31 1.26–1.37), indicating risk. Subgroup analysis confirmed this across various demographic factors, sensitivity reinforcing robustness findings. Conclusion establishes an independent predictor risk, importance postoperative management mitigating long‐term cognitive outcomes. Approximately 30% post‐CPSP presents opportunity reduction through effective strategies, emphasising need targeted interventions address critical healthcare issue. Significance provides compelling evidence that significantly increases previously underexplored connection decline. By establishing our findings underscore strategies surgical patients, particularly mitigate heightened improve

Language: Английский

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Association between preoperative albumin levels and postoperative delirium in geriatric hip fracture patients

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 14, 2024

Objective This study aims to examine the association between preoperative serum albumin levels and postoperative delirium (POD) in geriatric patients who have undergone hip fracture surgery, with goal of offering novel insights for clinical interventions targeting POD. Methods A retrospective analysis was conducted on medical records underwent surgery a tertiary institution from January 2013 November 2023. The were classified based hypoalbuminemia (defined as level < 35 g/L) threshold. Multivariable logistic regression propensity score matching (PSM) employed calculate adjusted odds ratios (OR) 95% confidence intervals (95% CI) POD eliminate potential confounding factors. Additionally, subgroup performed explore interaction effect. Results cohort included 1,440 patients, an incidence found be 19.1%. In multivariable analysis, had OR 2.99 (95%CI: 2.14–4.18) compared those normal (≥ g/L). Furthermore, significant trend observed across different severity categories, including mild (34.9–30.0 g/L; = 2.71, 95%CI: 1.84–3.99), moderate (29.9–25.0 g/L, 3.44, 1.88–6.28), severe (<25.0 3.97, 1.78–8.86), value p <0.001. Similar results PSM analysis. treating continuous variable, risk increased by 11% CI, 1.08–1.15) each 1 g/L decrease level. Conclusion Low are strongly associated fractures, dose–response relationship exists them.

Language: Английский

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Predilection for Perplexion: Preoperative microstructural damage is linked to postoperative delirium

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Postoperative delirium is the most common postsurgical complication in older adults and associated with an increased risk of long-term cognitive decline Alzheimer's disease (AD) related dementias (ADRD). However, neurological basis this risk- whether postoperative unmasks latent preoperative pathology or leads to AD-relevant after perioperative brain injury-remains unclear. Recent advancements neuroimaging techniques now enable detection subtle features damage that may underlie clinical symptoms. Among these, Neurite Orientation Dispersion Density Imaging (NODDI) can help identify microstructural damage, even absence visible macro-anatomical abnormalities. To investigate potential abnormalities function, we analyzed pre- post-operative diffusion MRI data from 111 patients aged ≥60 years who underwent non-cardiac/non-intracranial surgery. Specifically, investigated variation metrics within posterior cingulate cortex (PCC), a region which prior work has identified glucose metabolism alterations delirious brain, key early accumulation amyloid beta (Aβ) preclinical AD. We also examined relationship PCC NODDI function. Compared did not develop (n=99), found free water (FISO) neurite density index (NDI) decreased orientation dispersion (ODI) dorsal before surgery among those later developed (n=12). These FISO differences remained present at six weeks postoperatively, while these NDI ODI not. Preoperative values were positively attention/concentration performance, independent age, education level, global atrophy. Yet, correlated cerebrospinal fluid Aβ positivity levels. results suggest susceptibility delirium, AD-related (i.e., Aβ) neuropathology. Furthermore, linked deficits attention/concentration, core feature delirium. Our findings highlight vulnerability PCC, default mode network, as neuroanatomic locus explain link between vulnerable surgical patients.

Language: Английский

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Ulinastatin treatment mitigates glycocalyx degradation and associated with lower postoperative delirium risk in patients undergoing cardiac surgery: a multicentre observational study

Critical Care, Journal Year: 2025, Volume and Issue: 29(1)

Published: Jan. 29, 2025

Abstract Background Ulinastatin (UTI), recognized for its anti-inflammatory properties, holds promise patients undergoing cardiac surgery. This study aimed to investigate the relationship between intraoperative UTI administration and incidence of delirium following Methods A retrospective analysis was performed on a cohort 6,522 adult surgery evaluate treatment incident postoperative (POD) in ongoing followed by prospective observational 241 an vitro explore findings potential role preventing ischemia–reperfusion induced glycocalyx degradation. Results Both univariate multivariate logistic regression analyses indicated that associated with significant lower risk POD among patients, finding confirmed through employing propensity score matching. The subsequent further supported these (adjusted Odds Ratio = 0.392, 95% CI: 0.157–0.977, P 0.044). Furthermore, mitigated degradation, as demonstrated study. Conclusions may mitigate potentially lowering offering valuable insights future interventions prevent enhance patient outcomes. Trial registration number ClinicalTrials.gov (No. NCT06268249). Retrospectively registered 4 February 2024.

Language: Английский

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Clinical biomarkers of perioperative neurocognitive disorder: initiation and recommendation

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

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Peripheral blood mononuclear cell transcriptomic trajectories reveal dynamic regulation of inflammatory actors in delirium

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Abstract Delirium is a neurologic syndrome characterized by inattention and cognitive impairment frequently encountered in the medically ill. Peripheral inflammation key trigger of delirium, but patient-specific immune responses associated with delirium development resolution are unknown. This retrospective cohort study prospectively collected biospecimens examines RNA sequencing from peripheral blood mononuclear cells adults hospitalized for COVID-19 to better understand factors (n = 64). Longitudinal transcriptomic analyses highlight persistent dysregulation marked increasing expression trajectories genes linked innate pathways, including complement activation, cytokine production, monocyte/macrophage recruitment. Genes involved adaptive immunity showed declining trajectory over time patients delirium. Although corticosteroid treatment suppressed some aspects hyperactivation, aberrant contributing were exacerbated. was normalization transcripts such as CCL2 markers. Novel associations found related stress granule assembly DUSP2 KLF10 , which mediate T-cell responses. These findings provide insights into accompanying their modulation corticosteroids. Future trials targeting inflammatory may mitigate severe outcomes due COVID19.

Language: Английский

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Lipid Dysregulation and Delirium in Older Adults: A Review of the Current Evidence and Future Directions

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 224, P. 111299 - 111299

Published: March 12, 2025

Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with multifaceted etiology challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk developing delirium. Despite extensive research, single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests correlation between lipid dysregulation development elderly patients, especially This connection has led to proposed treatments targeting dyslipidemia associated neuroinflammatory effects acute-phase review aims synthesize current literature on the relationship older highlighting need further research into specific neurolipidome constituents age-related profile changes, potentially uncovering novel therapeutic strategies

Language: Английский

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Neuroinflammation—A Crucial Factor in the Pathophysiology of Depression—A Comprehensive Review

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 502 - 502

Published: March 30, 2025

Depression is a multifactorial psychiatric condition with complex pathophysiology, increasingly linked to neuroinflammatory processes. The present review explores the role of neuroinflammation in depression, focusing on glial cell activation, cytokine signaling, blood-brain barrier dysfunction, and disruptions neurotransmitter systems. article highlights how inflammatory mediators influence brain regions implicated mood regulation, such as hippocampus, amygdala, prefrontal cortex. further discusses involvement hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, kynurenine pathway, providing mechanistic insights into chronic inflammation may underlie emotional cognitive symptoms depression. bidirectional relationship between depressive emphasized, along peripheral immune responses systemic stress. By integrating molecular, cellular, neuroendocrine perspectives, this supports growing field immunopsychiatry lays foundation for novel diagnostic biomarkers anti-inflammatory treatment approaches Further research holds promise developing more effective personalized interventions individuals suffering from

Language: Английский

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