Effect of intranasal insulin on perioperative cognitive function in older adults: a randomized, placebo-controlled, double-blind clinical trial

Age and Ageing, Journal Year: 2024, Volume and Issue: 53(9)

Published: Aug. 31, 2024

Abstract Background Postoperative cognitive impairment are common neural complications in older surgical patients and exacerbate the burden of medical care on families society. Methods A total 140 who were scheduled for elective orthopaedic surgery or pancreatic with general anaesthesia randomly assigned to Group S I a 1:1 allocation. Patients received intranasal administration 400 μL normal saline 40 IU/400 insulin, respectively, once daily from 5 minutes before induction until 3 days postoperatively. Perioperative function was assessed using Mini-Mental State Examination (MMSE) Montreal Cognitive Assessment-Basic (MoCA-B) at 1 day after postoperative delirium (POD) incidence 3-minute Diagnostic Interview CAM (3D-CAM) 1–3. Serum levels interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), S100-β C-reactive protein (CRP) measured first surgery. Results Insulin treatment significantly increased MMSE MoCA-B scores group than (P < 0.001, P = respectively), decreased POD within 3-day period (10.9% vs 26.6%, 0.024), inhibited IL-6 compared 0.034, 0.044, respectively). Conclusions Intranasal insulin is thus suggested as potential therapy improve cognition undergoing However, more standardized multi-centre, large-sample study needed further validate these results.

Language: Английский

---

Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide

Microbiome, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 8, 2023

Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated neurological diseases; however, mechanisms by which microbiota regulates gastrointestinal and cognitive function incompletely understood.Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, immunofluorescence staining were employed to discern impacts of surgery on profiles, barriers, serum brain. Interventions in mice included fecal transplantation, anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid palmitic amide administration.Surgery-induced impairment occurs predominantly aged mice, surgery-induced alterations composition profile exacerbate barrier disruption mice. These adverse effects can be mitigated transferring from young donors or bolstering using Lactobacillus, acid. Moreover, profiles restored transplanting feces surgical improving neuropathology function, these coincide increased permeability. Metabolomic screening identified metabolites mouse after surgery, especially increase amide. Palmitic levels brain decreased Oral exacerbates neuropathological changes mice.Gut a key mechanism leading cognition dysfunction, disrupts metabolic abnormalities, resulting neuroinflammation dendritic spine loss. Intestinal damage high level old may cause incidence PND elderly. Preoperative regulation restoration benefit preventing PND. Video Abstract.

Language: Английский

---

Effects of regional cerebral oxygen saturation monitoring on postoperative cognitive dysfunction in older patients: a systematic review and meta-analysis

BMC Geriatrics, Journal Year: 2023, Volume and Issue: 23(1)

Published: March 6, 2023

Postoperative cognitive dysfunction (POCD) is common after surgery and anesthesia, particularly in older patients. It has been reported that regional cerebral oxygen saturation (rSO2) monitoring potentially influences the occurrence of POCD. However, its role prevention POCD remains controversial Additionally, quality evidence on this topic still relatively poor.The electronic databases PubMed, EMBASE, Web Science, Cochrane Library were systematically searched using indicated keywords from their inception to June 10, 2022. We limited our meta-analysis randomized controlled trials (RCTs) assessed effects rSO2 Methodological risk bias assessed. The primary outcome was incidence during hospitalization. secondary outcomes postoperative complications length hospital stay (LOS). Odds ratios (OR) 95% confidence intervals (CI) calculated determine complications. standardized mean difference (SMD) instead raw CI for LOS.Six RCTs, involving 377 patients, included meta-analysis. ranges 17 89%, with an overall prevalence 47% pooled analysis. Our results demonstrated rSO2-guided intervention could reduce patients undergoing non-cardiac (OR, 0.44; CI, 0.25 0.79; P = 0.006) rather than cardiac 0.69; 0.32 1.52; 0.36). Intraoperative also associated a significantly shorter LOS (SMD, -0.93; -1.75 -0.11; 0.03). Neither cardiovascular 1.12; 0.40 3.17; 0.83) nor surgical 0.78; 0.35 1.75; 0.54) affected by use monitoring.The lower surgery. This may have potential prevent high-risk populations. Further large RCTs are warranted support these preliminary findings.

Language: Английский

---

Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial

Journal of Clinical Anesthesia, Journal Year: 2023, Volume and Issue: 86, P. 111068 - 111068

Published: Feb. 1, 2023

To assess the impact of intraoperative dexmedetomidine on long-term outcomes older patients following major noncardiac surgery mainly for cancer.A follow-up enrolled in a randomized trial.The initial trial was performed tertiary care hospital Beijing, China.Patients aged 60 years or who were scheduled surgery.Participants to receive either (a loading dose 0.6 μg/kg over 10 min, followed by continuous infusion 0.5 μg/kg/h until 1 h before end surgery) placebo during anesthesia.The primary endpoint overall survival. Secondary endpoints included recurrence-free survival and event-free Cox proportional hazard models used adjust predefined confounding factors. Propensity score matching employed sensitive analysis.Among 620 trial, 619 analysis (mean age 69 years, 40% female, 77% oncological surgery). The median duration 42 months (interquartile range 41 45). Overall did not differ between two groups: there 49/309 (15.9%) deaths with versus 63/310 (20.3%) (adjusted ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free improved (68/309 [22.0%] events 98/310 [31.6%] placebo; adjusted HR 0.67, 0.49-0.92, 0.012). Event-free also (120/309 [38.8%] 145/310 [46.8%] 0.61-1.00, 0.047). Results similar after propensity-score subgroup cancer patients.In having cancer, improve but associated survivals.

Language: Английский

---

Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer’s Disease (Type 3 Diabetes)

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 95(4), P. 1301 - 1337

Published: Sept. 12, 2023

Malignant brain aging corresponds to accelerated age-related declines in functions eventually derailing the self-sustaining forces that govern independent vitality. establishes path toward dementing neurodegeneration, including Alzheimer's disease (AD). The full spectrum of AD includes progressive dysfunction neurons, oligodendrocytes, astrocytes, microglia, and microvascular systems, is mechanistically driven by insulin insulin-like growth factor (IGF) deficiencies resistances with accompanying deficits energy balance, increased cellular stress, inflammation, impaired perfusion, mimicking core features diabetes mellitus. underlying pathophysiological derangements result mitochondrial dysfunction, abnormal protein aggregation, oxidative endoplasmic reticulum aberrant autophagy, post-translational modification proteins, all which are signature both dysregulated insulin/IGF-1-mechanistic target rapamycin (mTOR) signaling. This article connects dots from benign malignant neurodegeneration reviewing salient pathologies associated initially adaptive later dysfunctional mTOR signaling brain. Effective therapeutic preventive measures must be two-pronged designed 1) address complex shifting impairments through re-purpose effective anti-diabetes therapeutics brain, 2) minimize impact extrinsic mediators transitions, e.g., inflammatory states, obesity, systemic resistance diseases, repeated bouts general anesthesia, minimizing exposures or implementing neuroprotective measures.

Language: Английский

---

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Nov. 29, 2023

Cognitive impairments, such as learning and memory deficits, may occur in susceptible populations including the elderly patients who are chronically ill or have experienced stressful events, surgery, infection, trauma. Accumulating lines of evidence suggested that peripheral inflammation featured by recruitment immune cells release pro-inflammatory cytokines be activated during aging these conditions, participating system-brain communication. Lots progress has been achieved deciphering core bridging mechanism connecting cognitive which helpful developing early diagnosis, prognosis evaluation, prevention methods based on blood circulation system sampling intervention. In this review, we summarized evolving prevalence inflammation-associated neurocognitive impairments discussed research advances underlying mechanisms. We also highlighted treatment strategies against dysfunction.

Language: Английский

---

Oral administration of ellagic acid mitigates perioperative neurocognitive disorders, hippocampal oxidative stress, and neuroinflammation in aged mice by restoring IGF-1 signaling

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 30, 2024

Abstract This study investigates the potential of ellagic acid (EA), a phytochemical with antioxidant and anti-inflammatory properties, in managing perioperative neurocognitive disorders (PND). PND, which represents spectrum cognitive impairments often faced by elderly patients, is principally linked to surgical anesthesia procedures, heavily impacted oxidative stress hippocampus microglia-induced neuroinflammation. Employing an aged mice model subjected abdominal surgery, we delve into EA's ability counteract postoperative cerebral inflammation engaging Insulin-like growth factor-1 (IGF-1) pathway. Our findings revealed that administering EA orally notably alleviated post-surgical decline older mice, fact was manifested improved performance during maze tests. enhancement behavioral EA-treated corresponded rejuvenation IGF-1 signaling, decrease markers (like MDA carbonylated protein), increase activity enzymes such as SOD CAT. Alongside these, observed microglia-driven neuroinflammation hippocampus, thus underscoring roles EA. Interestingly, when given conjunction IGF1R inhibitor, these benefits were annulled, accentuating pivotal role pathway plays neuroprotective Hence, could serve potent candidate for safeguarding against PND patients curbing through activation

Language: Английский

---

Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: March 26, 2024

With the aging of population, health elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in patients following general anesthesia or surgery. It characterized by decline that may persist for weeks, months, even longer. Electroacupuncture (EA), novel therapy combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as therapeutic intervention preventing and treating POCD, particularly patients. Although beneficial effects EA on POCD have been explored preclinical clinical studies, reliability limited methodological shortcomings, underlying mechanisms remain largely unexplored. Therefore, we synthesized existing evidence proposed biological neuroinflammation, oxidative stress, autophagy, microbiota-gut-brain axis, epigenetic modification. This review summarizes recent advances provides theoretical foundation, explores molecular prevention offers basis conducting relevant trials.

Language: Английский

---

Effects of nonintubated thoracoscopic surgery on postoperative neurocognitive function: a randomized controlled trial

European Journal of Cardio-Thoracic Surgery, Journal Year: 2024, Volume and Issue: 65(1)

Published: Jan. 1, 2024

Abstract OBJECTIVES Postoperative neurocognitive disorder following thoracoscopic surgery with general anaesthesia may be linked to reduced intraoperative cerebral oxygenation and perioperative inflammation, which can potentially exacerbated by mechanical ventilation. However, nonintubated surgery, utilizes regional maintains spontaneous breathing, provides a unique model for studying the potential benefits of avoiding This approach allows investigation into impact on profiles, inflammatory responses oxygen levels. METHODS In total, 110 patients undergoing were randomly equally assigned intubated group group. Regional was monitored during surgery. Serum neuroinflammatory biomarkers, including interleukin-6 glial fibrillary acidic protein, measured at baseline (before surgery) 24 h after complication severity compared using Comprehensive Complication Index. The primary outcome changes in test score, assessed baseline, 6 months RESULTS Patients had higher scores (69.9 ± 10.5 vs 65.3 11.8; P = 0.03) (70.6 6.7 65.4 8.1; < 0.01) significantly over time one-lung ventilation (P 0.03). revealed postoperative serum level (group interaction, 0.04) trend towards protein 0.11). Furthermore, lower Index (9.0 8.2 6.1 7.1; 0.05). CONCLUSIONS Nonintubated associated improved recovery, more stable oxygenation, ameliorated inflammation attenuated severity.

Language: Английский

---

The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: May 1, 2024

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery patients, leads to prolonged hospital stay, reduced quality life, increased medical costs, even higher mortality. There no definite effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve function reduce incidence Therefore, our studies summarize current interventions from aspects training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain sleep improvement, music therapy, environment, multimodal combination Interventions, provide more data clinical application research.

Language: Английский

---