Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

La aplicación del saber médico. Hipertensión y daño cognitivo

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Introduction: High blood pressure (HBP) is the leading cause of death from cardiovascular disease. Despite the advances, the percentage of undiagnosed and untreated hypertensive patients is 58.4%. The evaluation of cognitive damage in HBP focuses on preventing stroke, while functional damage is ignored. This inadequate management may be multifactorial. The objective was to analyze the opinions that doctors have about the relationship between high blood pressure and cognitive damage. Methodology: Observational, descriptive, cross-sectional study developed in the period between August 2020 and August 2023. Analysis of data obtained from a self-administered, anonymous and voluntary questionnaire. Revealing information on the professional profile, knowledge of HBP, its link with cognitive impairment (CD), diagnosis and treatment. Results: 222 professionals were included, 215 (96.8%) agree with the existence of a link between HBP and other cardiovascular risk factors in CD, and 218 (98.1%) acknowledge assisting patients at risk of suffering from CD. The CD evaluation is carried out in selected cases by 132 (59.4%) participants and 59 (26.7%) always do it. Of those who perform evaluation, 103 (54%) use the Mini Mental State Examination (MMSE), 10 (5.2%) use the Montreal Cognitive Assessment (MoCA) and 9 (4.7%) use the Clock Drawing Test. Regarding the decrease in blood pressure in elderly patients and the link with risk of CD: 54 (24.3%) do not recognize risk and 65 (29.2%) recognize a moderate-high risk. In reference to the implication of the treatment of cardiovascular disease and CD: 217 (97.7%) recognized a beneficial effect. Discussion: Given the recognition of the link between HBP and CD, it would be expected that CD would be investigated in the vast majority, however only 26.7% always evaluate it. There is no consensus on the method, the MMSE being the most used, with a low application of the MoCA test and/or Clock Drawing Test, the latter being the ones that evaluate executive function, mostly altered in CD linked to HBP. Although the treatment of cardiovascular disease is recognized as beneficial with respect to CD, the control of HBP in older adults is considered risky. A diagnosis is made of a situation where a disparity is evident between what one recognizes as knowing and what one claims to do. Conclusions: The role of vascular disease in functional brain damage is recognized, considering it necessary to know the cognitive status of patients, however there is a low application of screening tests that evaluate executive function. In this context, a gap between medical knowledge and practice is shown.

Introdução: A hipertensão arterial (HA) é a principal causa de morte por doenças cardiovasculares. Apesar dos avanços, o percentual de hipertensos não diagnosticados e não tratados é de 58,4%. A avaliação do dano cognitivo na hipertensão concentra-se na prevenção do acidente vascular cerebral, enquanto o dano funcional é ignorado. Esse manejo inadequado pode ser multifatorial. É objetivo fue analisar a opinião dos médicos sobre a relação entre hipertensão arterial e danos cognitivos. Metodologia: Estudo observacional, descritivo, transversal desenvolvido no período entre agosto de 2020 e agosto de 2023. Análise de dados obtidos a partir de questionário autoaplicável, anônimo e voluntário. Revelar informações sobre o perfil profissional, conhecimento sobre a HA, sua ligação com o comprometimento cognitivo (DC), diagnóstico e tratamento. Resultados: Foram incluídos 222 profissionais, 215 (96,8%) concordam com a existência de ligação entre hipertensão e outros fatores de risco cardiovascular na DC e 218 (98,1%) reconhecem ajudar pacientes com risco de sofrer de D.C. A avaliação da DC é realizada em casos selecionados por 132 (59,4%) participantes e 59 (26,7%) a fazem sempre. Dos que realizam avaliação, 103 (54%) utilizam o Mini Exame do Estado Mental (MEEM), 10 (5,2%) utilizam a Avaliação Cognitiva de Montreal (MoCA) e 9 (4,7%) utilizam o Clock Drawing Test. Em relação à diminuição da pressão arterial em pacientes idosos e a ligação com o risco de DC: 54 (24,3%) não reconhecem risco e 65 (29,2%) reconhecem risco moderado-alto. Em referência à implicação do tratamento de doenças cardiovasculares e DC: 217 (97,7%) reconheceram o efeito benéfico. Discussão: Dado o reconhecimento da ligação entre hipertensão e DC, seria de esperar que a DC fosse investigada na grande maioria, no entanto apenas 26,7% sempre a avaliam. Não há consenso sobre o método, sendo o MEEM o mais utilizado, com baixa aplicação do teste MoCA e/ou Clock Drawing Test, sendo estes últimos os que avaliam a função executiva, majoritariamente alterada nos DC vinculados à HA. Embora o tratamento das doenças cardiovasculares seja reconhecido como benéfico em relação à DC, o controle da HA em idosos é considerado arriscado. É feito um diagnóstico de uma situação em que é evidente uma disparidade entre o que se reconhece como saber e o que se afirma fazer. Conclusões: O papel da doença vascular no dano cerebral funcional é reconhecido, considerando-se necessário conhecer o estado cognitivo dos pacientes, porém há baixa aplicação de testes de triagem que avaliam a função executiva. Nesse contexto, evidencia-se uma lacuna entre o conhecimento e a prática médica.

Dexmedetomidine for Postoperative Delirium Prevention in the Older Adult: An Integrative Review.

The brain and cognition are particularly vulnerable to anesthetic and surgical insults, with postoperative delirium being the most common postoperative complication in patients aged ≥ 65 years. The body releases psychoactive proinflammatory cytokines in response to surgical trauma, including interleukin-1ß, interleukin-6, and tumor necrosis factor-α. This promotes a porous blood-brain barrier, promoting postoperative cognitive dysfunction. Aging adults lose brain volume, cerebrospinal fluid, and dendritic synapses, thereby increasing neurologic stress and vulnerability to these surgical changes. Anesthetic technique influences the process, necessitating the importance of educated certified registered nurse anesthetists. Dexmedetomidine, a nonspecific α2-adrenergic receptor agonist, exhibits anti-inflammatory properties that counteract the proinflammatory mechanisms initiated by surgical insult. Additionally, dexmedetomidine mimics natural sleep pathways and reduces opioid dosing requirements, promoting cognitive preservation. While further research is required to establish an association with long-term effects, current literature indicates that dexmedetomidine may reduce postoperative delirium and cognitive dysfunction in older adults through various dosing regimens. This journal course reviews the pathophysiology of postoperative neurocognitive dysfunction and delirium, dexmedetomidine as an adjunct to mitigate these pathologic changes, and the current literature on dexmedetomidine's impact on postoperative delirium in older adults.

Acupuncture improves spatial learning and memory impairment caused by herpes simplex virus type-1 in rats through the p38 MAPK/CREB pathway.

BACKGROUND: Acupuncture can improve herpes simplex encephalitis (HSE), but the underlying mechanism is not clear. Therefore, we evaluated the cognitive function and apoptosis in hippocampus caused by herpes simplex virus type-1 (HSV-1) in rats after acupuncture and described the molecular mechanism. METHODS: Sprague-Dawley rats were induced into HSE models by HSV-1 infection. After 3 days, they received acupuncture at the acupoints of Xuanzhong (GB39), Baihui (GV20), Shenmen (HT7), Shenting (GV24), and Sanyinjiao (SP6), and/or intraperitoneal injection of the p38 MAPK inhibitor SB203580. Morris water maze test was performed on rats. The hippocampus of rats was obtained, and the expression of apoptosis-related genes in the tissues was detected by qRT-PCR. In addition, apoptosis-related proteins and proteins related to the p38 MAPK/CREB pathway in the tissues was detected by western blot. RESULTS: After HSV-1 induction, the rat's escape latency was increased, the time spent on the platform in the target quadrant and the number of platform crossings significantly decreased. In addition, there was an increase in apoptosis in the hippocampus, accompanied by elevated levels of p-p38 and decreased levels of p-CREB. However, these effects could be improved by acupuncture treatment. Interestingly, SB203580 plays a similar role to acupuncture, and acupuncture could further enhance the impacts of SB203580 on cognitive function and apoptosis in hippocampus in HSE rats. CONCLUSION: Acupuncture improves spatial learning and memory impairment caused by HSV-1 in rats. The functional mechanism of acupuncture may be through the p38 MAPK/CREB pathway.

Interactive effect of diabetes mellitus and subclinical MRI markers of cerebrovascular disease on cognitive decline and incident dementia: a memory-clinic study.

BACKGROUND: Cognitive impairment is an increasingly recognized comorbidity of diabetes, yet the mechanisms underlying this association remain poorly understood. This knowledge gap has contributed to conflicting findings regarding the impact of diabetes on long-term cognitive outcomes in older adults. The presence of cerebrovascular disease (CeVD) may potentially modify this relationship. However, interactive effect between diabetes and subclinical MRI markers of CeVD on cognitive trajectories and incident dementia remains unexplored. METHODS: A total of 654 participants underwent brain MRI at baseline, from whom 614 with at least one follow-up were selected for longitudinal analysis. Cognitive tests were performed annually up to 5 years. CeVD markers of interest were lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), cortical microinfarcts (CMIs), intracranial stenosis (ICS), and cortical infarcts. Blood-based Alzheimer biomarkers, including p-tau181 and p-tau181/Aß42 ratio, were used as indicators of Alzheimer pathology. RESULTS: At baseline, diabetes was associated with lower cognitive performance and higher burden of CeVD, but not p-tau181 or p-tau181/Aß42 ratio. Longitudinally, we found an interactive effect of diabetes and WMHs, rather than an independent effect of diabetes, on cognitive decline and dementia risk. Subgroup analyses showed association of diabetes with cognitive outcomes was stronger in participants with high WMHs load but non-significant in those with low WMHs load. Moreover, these associations remained unchanged after adjusting for blood-based Alzheimer biomarkers. CONCLUSIONS: The effect of diabetes on cognitive decline is contingent upon the presence of WMHs and independent of Alzheimer's pathology. This finding raises the possibility of utilizing WMHs as an imaging biomarker to identify diabetic subgroup at greater risk of developing cognitive impairment. Furthermore, therapeutic interventions targeting WMHs may prevent cognitive deterioration in older adults with diabetes.

Lithium-induced cognitive dysfunction assessed over 1-year hospitalisation: A case report.

Introduction: Lithium-induced neurotoxicity is almost always reversible but can cause irreversible neurological sequelae, namely the syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). As there is no definitive treatment for SILENT, caution is required when administering lithium. Reports on the effect of lithium-effectuated neurotoxicity on cognitive function are limited. We report a case in which high cognitive function was lost after lithium overdose and hardly recovered, as evaluated using multiple neuropsychological tests during a 1-year hospitalisation period. Patient presentation: A 52-year-old man on lithium medication with bipolar disorder was admitted to the intensive care unit because of lithium overdose. The patient achieved lucid consciousness after continuous haemodiafiltration. However, he could not move his body as desired or produce appropriate verbal expressions; thus, he was moved to our psychiatric ward, where his treatment continued. Management and outcome: After several months, the patient was diagnosed with SILENT owing to persistent motor and cognitive dysfunctions. Multiple neuropsychological tests were performed, and cognitive function was evaluated. The Neurobehavioural Cognitive Status Examination showed a worsening trend, and the full intelligence quotient of the Wechsler Adult Intelligence Scale-Third Edition was in the mild intellectual disability range. Conclusion: This is a clear case of cognitive dysfunction due to SILENT and is difficult to treat. Thus, it is crucial to prevent the onset of SILENT. Contribution: This report is valuable because it is one of the few to track changes in cognitive function over time in a patient with SILENT using objective measures over 1 year of hospitalisation.

MEF2C Alleviates Postoperative Cognitive Dysfunction by Repressing Ferroptosis.

BACKGROUND: Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as a potential etiology for postoperative cognitive dysfunction (POCD). Myocyte-specific enhancer factor 2C (MEF2C), a transcription factor expressed in various brain cell types, has been implicated in cognitive disorders. This study sought to ascertain whether MEF2C governs postoperative cognitive capacity by affecting ferroptosis. METHODS: Transcriptomic analysis of public data was used to identify MEF2C as a candidate differentially expressed gene in the hippocampus of POCD mice. The POCD mouse model was established via aseptic laparotomy under isoflurane anesthesia after treatment with recombinant adeno-associated virus 9 (AAV9)-mediated overexpression of MEF2C and/or the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Cognitive performance, Nissl staining, and ferroptosis-related parameters were assessed. Dual-luciferase reporter gene assays and chromatin immunoprecipitation assays were implemented to elucidate the mechanism by which MEF2C transcriptionally activates GPX4. RESULTS: MEF2C mRNA and protein levels decreased in the mouse hippocampus following anesthesia and surgery. MEF2C overexpression ameliorated postoperative memory decline, hindered lipid peroxidation and iron accumulation, and enhanced antioxidant capacity, which were reversed by RSL3. Additionally, MEF2C was found to directly bind to the Gpx4 promoter and activate its transcription. CONCLUSIONS: Our findings suggest that MEF2C may be a promising therapeutic target for POCD through its negative modulation of ferroptosis.

Postoperative delirium: A tragedy for elderly cancer patients.

In this editorial, we comment on the article by Hu et al entitled "Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique". We wanted to draw attention to the general features of postoperative delirium (POD) as well as the areas where there are uncertainties and contradictions. POD can be defined as acute neurocognitive dysfunction that occurs in the first week after surgery. It is a severe postoperative complication, especially for elderly oncology patients. Although the underlying pathophysiological mechanism is not fully understood, various neuroinflammatory mechanisms and neurotransmitters are thought to be involved. Various assessment scales and diagnostic methods have been proposed for the early diagnosis of POD. As delirium is considered a preventable clinical entity in about half of the cases, various early prediction models developed with the support of machine learning have recently become a hot scientific topic. Unfortunately, a model with high sensitivity and specificity for the prediction of POD has not yet been reported. This situation reveals that all health personnel who provide health care services to elderly patients should approach patients with a high level of awareness in the perioperative period regarding POD.

Association of sleep quality with cognitive dysfunction in middle-aged and elderly adults: a cross-sectional study in China.

Objectives: Sleep is an indispensable part of human health, which can help us to restore physical strength, enhance immunity and maintain nervous system stability. The relationship between sleep quality and cognitive dysfunction is unclear, especially at the community population level. This study aims to explore the association between sleep quality and cognitive dysfunction. Methods: A total of 5,224 community residents were enrolled in this cross-sectional study. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Sleep quality was assessed by the multidimensional sleep questionnaire. Multivariate logistic regression was used to analyze the association between sleep quality and cognitive dysfunction. The adjusted models took into account relevant demographic, clinical, and sleep variables. Results: A total of 3,106 participants were enrolled in this study, of whom 463 (15%) had cognitive dysfunction. Total sleep duration, staying up, sleep latency, number of awakenings, and history of sleep medications were associated with cognitive dysfunction in unadjusted models, and these effects were consistent after adjustment. First, those who slept 6-7.9 h per day (OR = 0.57, 95% CI 0.40 to 0.80, p = 0.001) had a lower risk for cognitive dysfunction compared to those who slept less than 6 h per day. Second, participants who stayed up more than 10 times over the 3 months (OR = 1.90, 95% CI 1.20 to 3.00, p = 0.006) were more likely to suffer cognitive dysfunction than those who never stayed up. Third, we also found that participants with sleep latencies of 16-30 min were less likely to experience cognitive dysfunction than those with sleep latencies of less than 16 min after adjusting confounders (OR = 0.33, 95% CI 0.23 to 0.47, p < 0.001). Fourth, participants who woke up once (OR = 1.65, 95% CI 1.19 to 2.30, p = 0.003) and three or more times (OR = 2.34, 95% CI 1.25 to 4.36, p = 0.008) after falling asleep had a higher risk than those who did not wake up at night. Last, participants taking sleep medication (OR = 2.97, 95% CI 1.19 to 7.45, p = 0.020) were more vulnerable to cognitive dysfunction, relative to participants without taking any medications. Conclusion: Our results suggest that after adjustment for potential confounding variables, poor sleep quality is associated with cognitive dysfunction.

Investigating the relationship between cognitive impairment and brain white matter tracts using diffusion tensor imaging in patients with prolactinoma.

BACKGROUND: Cognitive impairment is known to occur in patients with prolactinoma, but the underlying mechanism is unclear. OBJECTIVE: To evaluate cognitive function in patients with prolactinoma and to investigate the basis of possible cognitive impairment in brain white matter changes using diffusion tensor imaging (DTI). METHODS: 37 consecutive patients with prolactinoma and 37 healthy controls of similar age, sex, and education were enrolled in the study. Hormone levels were determined in all participants, comprehensive neuropsychological testing was performed, and DTI was used to reconstruct and evaluate white matter tracts. RESULTS: In patients with prolactinoma, short- and long-term visual and verbal memory, attention, concentration, and executive and language functions were impaired compared to the healthy group. When comparing the DTI results, lower fractional anisotropy (FA) values were found in the patients' right uncinate fasciculus (R-UF), indicating neuronal damage. After applying the Bonferroni correction, the two groups had no significant difference in 42 tracts (p > 0.0012 for all). A positive correlation was found between poor FA scores on the R-UF and low scores on long-term memory, category and letter fluency tests. In addition, patients with hypoprolactinemia had the worst short-term memory scores, while normoprolactinemia had the best scores. Also, the poorer R-UF FA values were found in the patients with hypoprolactinemia and the highest in those with normoprolactinemia. CONCLUSION: This study is the first to investigate reasons for cognitive dysfunction in patients with prolactinoma by DTI. No significant structural changes were found in brain tracts of patients with prolactinoma. Still, there may be a link between potential damage in the R-UF and cognitive dysfunction, and further research is needed. In addition, the results showed that the development of hypoprolactinemia is associated with cognitive dysfunction and emphasized that overtreatment should be avoided.

Mendelian Randomization Analysis to Assess Whether Magnetic Resonance Imaging Signs of Cerebral Small Vessel Disease Can Cause Cognitive Decline and Dementia.

OBJECTIVE: Cognitive decline and dementia have been linked to cerebral small vessel disease, so we explored using Mendelian randomization whether cerebral small vessel disease visible as 10 neuroimaging signs may cause cognitive decline and dementia. METHODS: We analyzed publicly available data from genome-wide association studies using two-sample Mendelian randomization involving inverse variance weighting, weighted median, MR-Egger, and MR-PRESSO approaches. RESULTS: Mendelian randomization suggested that cognitive decline can be caused by lacunar stroke (inverse variance weighting, ß = -0.012, 95% CI -0.024 to -0.001, P = 0.033). Furthermore, an elevated burden of white matter hyperintensities was associated with an increased risk of Dementia due to Parkinson's disease (inverse variance weighting, OR 2.035, 95% CI 1.105 to 3.745, P = 0.023). Notably, no significant associations were observed between neuroimaging markers of Cerebral Small Vessel Disease and other types of dementia. CONCLUSION: This Mendelian randomization study provides evidence that lacunar stroke and white matter lesions can cause cognitive decline, and that white matter hyperintensity may increase risk of dementia due to Parkinson's disease. These results underscore the need for further investigations into the neurocognitive effects of cerebral small vessel disease.

Gut Microbiota and Probiotics in Perioperative Management: A Narrative Review.

The human gut is the abode of several complex and diverse microbes. It is a fact that the human brain is interconnected with the spinal cord and sense organs; however, there is also a possibility of a connection between the brain and the gut microbiome. The human gut can be altered in various ways, the principal method being the intake of prebiotics, probiotics and synbiotics. Can this alteration in the gut microbiome be clinically utilised in the perioperative period? We conducted a literature search related to this topic using databases and search engines (Medical Literature Analysis and Retrieval System Online {MEDLINE}, Embase, Scopus, PubMed and Google Scholar). The search revealed some preclinical and clinical studies in animals and humans that demonstrate the alteration of the gut microbiome with the use of anxiolysis, probiotics/prebiotics and other perioperative factors including opioids, anaesthetics and perioperative stress. The significant effects of this alteration have been seen on preoperative anxiety and postoperative delirium/cognitive dysfunction/pain. These effects are described in this narrative review, which opens up newer vistas for high-quality research related to the gut microbiome, gut-brain axis, the related signaling pathways and their clinical application in the perioperative period.

Highlighting the Neuropsychological Consequences of COVID-19: Evidence From a Narrative Review.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2, although largely affecting the respiratory system, commonly presents with numerous clinical symptoms from other systems. COVID-19 has been associated with both acute and persistent neurological abnormalities in a substantial proportion of patients. Notably, post-COVID-19 neuropsychological abnormalities have garnered attention, highlighting a high prevalence of neurocognitive issues in affected individuals. This narrative review synthesizes current knowledge on the neuropsychological impact of COVID-19, drawing insights from an extensive online search of published literature conducted in the PubMed (MEDLINE) and Scopus databases. The findings underscore significant neuropsychological effects of COVID-19 observed at both individual and societal levels during the ongoing pandemic. Neuropsychological deficits such as memory difficulties, attention problems, and executive dysfunction, alongside physical symptoms like headaches and fatigue were commonly reported. Additionally, psychological challenges, including fear, anxiety, and depression, emerged as prevalent issues arising from the uncertainties surrounding the situation, social isolation, and employment insecurities. The identified neuropsychological manifestations of COVID-19 can significantly impede normal cognitive and emotional functioning, potentially resulting in decreased productivity and an overall decline in mental health and quality of life. Early identification of signs indicative of neurological or psychological decline becomes imperative, offering a crucial opportunity to mitigate the risk of long-term neuropsychological dysfunction through the development of targeted interventions.

Association between frailty index and cognitive dysfunction in older adults: insights from the 2011-2014 NHANES data.

Background: As the population ages, the occurrence of cognitive decline and dementia is continuously increasing. Frailty is a prevalent problem among older adults. Epidemiologic studies have shown a comorbidity between frailty and cognitive impairment. However, their relationship remains unclear. The frailty index is an important indicator for measuring frailty. This study aims to investigate the relationship between frailty index and cognitive dysfunction in older adults aged 60 years and older in the United States from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Methods: Community-dwelling older adults aged 60 years or older from 2011 to 2014 were extracted from the NHANES database. The frailty index was calculated using the formula: frailty index = total number of deficits present/total number of deficits measured. The Animal Fluency (AF), the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's disease Delayed Recall (CERAD-DR), and Word Learning (CERAD-WL) were used to evaluate cognitive dysfunction. Firstly, weighted logistic regression analysis was used to explore the relationship between frailty index and cognitive dysfunction. Secondly, the influence of covariates on the frailty index was evaluated by subgroup analysis and interaction. Finally, the non-linear relationship is discussed by using the restricted cubic spline regression model. Results: Our study included a total of 2,574 patients, weighted logistic regression analysis, after adjusting for all covariates, showed that the frailty index was associated with every test score. The interaction showed that covariates had no significant effect on this association in AF. The association between the frailty index and AF in the restricted cubic spline regression model is non-linear. As the frailty index increased, the risk of AF reduction increased, suggesting a higher risk of cognitive dysfunction. Conclusion: In general, a high frailty index appears to be associated with an increased risk of cognitive dysfunction in the elderly. Consequently, protecting against cognitive decline necessitates making geriatric frailty prevention and treatment top priorities.

The Combination of Presurgical Cortical Gray Matter Volumetry and Cerebral Perfusion Improves the Efficacy of Predicting Postoperative Cognitive Impairment of Elderly Patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. MATERIALS AND METHODS: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. RESULTS: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. CONCLUSIONS: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.

Cortical activation and functional connectivity during a verbal fluency task in patients with chronic insomnia: A multi-channel NIRS study.

BACKGROUND: Patients with chronic insomnia exhibit varying degrees of cognitive dysfunction. Functional connectivity of different brain regions contributes to the understanding of underlying cognitive processes in the cerebral cortex. However, this has not yet been studied in patients with chronic insomnia. This study aimed to elucidate the differences between brain activity patterns in patients with chronic insomnia and healthy controls (HCs) using a verbal fluency task (VFT). METHODS: We recruited 84 patients with chronic insomnia and 81 HCs. Oxy-haemoglobin (Oxy-Hb) concentrations in the brains of the participants were monitored using functional near-infrared spectroscopy (fNIRS) while performing the VFT. RESULTS: During the task period, no significant difference was observed between the VFT results of the two groups; patients with chronic insomnia showed significantly less cortical activation in haemodynamic responses of oxy-Hb at channels and brain regions mainly located in the prefrontal cortex compared to HCs (FDR-corrected p < 0.05). Moreover, the average channel-to-channel connectivity strength of patients in the chronic insomnia group was lower than that of those in the HC group (t = -6.717, p < 0.001). CONCLUSION: Our study provides neurological evidence for the dynamic detection of executive function in patients with chronic insomnia. Compared to HCs, patients with chronic insomnia exhibit weaker levels of brain activity and reduced task-related functional connectivity.

The mechanisms, hallmarks, and therapies for brain aging and age-related dementia.

Age-related cognitive decline and dementia are significant manifestations of brain aging. As the elderly population grows rapidly, the health and socio-economic impacts of cognitive dysfunction have become increasingly significant. Although clinical treatment of dementia has faced considerable challenges over the past few decades, with limited breakthroughs in slowing its progression, there has been substantial progress in understanding the molecular mechanisms and hallmarks of age-related dementia (ARD). This progress brings new hope for the intervention and treatment of this disease. In this review, we categorize the latest findings in ARD biomarkers into four stages based on disease progression: healthy brain, pre-clinical, mild cognitive impairment, and dementia. We then systematically summarize the most promising therapeutic approaches to prevent or slow ARD at four levels: genome and epigenome, organelle, cell, and organ and organism. We emphasize the importance of early prevention and detection, along with the implementation of combined treatments as multimodal intervention strategies, to address brain aging and ARD in the future.

Tryptophan-rich diet and its effects on Htr7+ Tregs in alleviating neuroinflammation and cognitive impairment induced by lipopolysaccharide.

BACKGROUND: Neuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer's, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role. METHODS: Mice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1-/-) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7. RESULTS: In this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1-/- mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment. CONCLUSIONS: Our research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

Cognitive impairment of medicated patients with remitted depression and low anticholinergic activity.

BACKGROUND: A recent meta-analysis has found that patients who have achieved remission of major depressive disorder (MDD) show cognitive dysfunction. Moreover, anticholinergic activity levels are associated with cognitive dysfunction, although the extent of these effects is unclear. Therefore, we measured serum anticholinergic activity (SAA) in blood samples of patients with remitted MDD and examined its relationship with cognitive function. METHODS: We recruited 49 patients with remitted MDD following treatment and 165 healthy subjects. Subjects completed the Stroop test and the logical memory (LM) and visual reproduction (VR) subtests from the Wechsler Memory Scale-Revised. We compared cognitive function scores among those with SAA below the limit of quantification (SAA [-]), those with SAA above the limit of quantification (SAA [+]), and healthy controls. RESULTS: The SAA (+) group scored significantly lower (p < 0.001) than the healthy control group on all tests, and the VR score of the SAA (-) group was significantly lower than that of the healthy control group (p = 0.024). LM scores in the SAA (+) group were significantly lower than that of the SAA (-) group (p = 0.033). Multiple regression analysis revealed a significant effect of SAA on the LM score (p = 0.015). LIMITATIONS: Our study was a cross-sectional analysis of a small number of patients. CONCLUSIONS: Our results support previous findings that the anticholinergic effect of antidepressants adversely affects cognitive function. Additionally, the cognitive impairment observed may persist because of MDD.

Vascular Impairment, Muscle Atrophy, and Cognitive Decline: Critical Age-Related Conditions.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the muscle mass reduction seen in sarcopenia and the decline in neuronal function characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient outcomes. This study emphasizes the complex interplay between vascular dysfunction, muscle degeneration, and cognitive decline, highlighting the necessity for multidisciplinary treatment approaches. Advances in this domain promise improved diagnostic accuracy, more effective therapeutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.