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Advanced age increases the risk of severe disease from SARS‐CoV‐2 infection, as well as incidence of long COVID and SARS‐CoV‐2 reinfection. We hypothesized that perturbations in the aged antiviral CD8+ T cell response predisposes elderly individuals to severe coronavirus infection, re‐infection, and postinfectious cognitive sequelae. Using MHV‐A59 as a murine model of respiratory coronavirus, we found that aging increased CNS infection and lethality to MHV infection. This was coupled with increased CD8+ T cells within the aged CNS but reduced antigen specificity. Aged animals also displayed a decreased proportion of CD103+ resident memory cells (TRM), which correlated with increased severity of secondary viral challenge. Using a reciprocal adoptive transfer paradigm, data show that not only were fewer aged CD8+ T cells retained within the adult brain post‐infection, but also that adult CD8+ cells expressed lower levels of TRM marker CD103 when in the aged microenvironment. Furthermore, aged animals demonstrated spatial learning impairment following MHV infection, which worsened in both aged and adult animals following secondary viral challenge. Spatial learning impairment was accompanied by increased TUNEL positivity in hippocampal neurons, suggestive of neuronal apoptosis. Additionally, primary cell coculture showed that activated CD8+ T cells induced TUNEL positivity in neurons, independent of antigen‐specificity. Altogether, these results show that non‐antigen specific CD8+ T cells are recruited to the aged brain and cause broad neuronal death without establishing a TRM phenotype that confers lasting protection against a secondary infection. [ABSTRACT FROM AUTHOR]

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1 420 941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. We assessed neurodevelopmental outcomes at age 6 years using the validated Korean Developmental Test, covering 6 major domains, with propensity score-based inverse probability weighting including consideration of covariates sex, birth weight, changes in body weight from birth to 4–6 months of age, head circumference at 4–6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5451 children with rotavirus hospitalization and 310 874 unexposed individuals revealed heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6 year olds. [ABSTRACT FROM AUTHOR]

Background: The Stroop task was used to investigate differences in cognitive function between Long COVID (LC), Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and healthy control subjects. Methods: Subjects viewed four color words or neutral (XXXX) stimuli with the same (congruent) or different color ink (incongruent). Cognitive conflict was inferred from response times for pairings of prestimuli and subsequent stimuli. Overall effects were assessed by univariate analysis with time courses determined for binned response times. Results: LC and ME/CFS had significantly longer response times than controls indicating cognitive dysfunction. Initial response times were ranked LC > ME > HC, and decreased according to power functions. At the end of the task (900s), times were ranked LC = ME > HC. Response times were significantly slower for stimuli following an incongruent prestimulus. Time series for Stroop effect, facilitation, interference, surprise index and practice power law parameters were generally similar in LC, ME/CFS and HC suggesting comparable patterns for recruitment of cognitive resources. The prestimulus data were analyzed and generated positive Stroop and interference effects that were distinct from stimulus effects. Conclusion: LC and ME/CFS have global slowing of response times that cannot be overcome by practice suggesting impaired communications between network nodes during problem solving. Analysis of matched prestimulus – stimulus effects adds a new dimension for understanding cognitive conflict. Brief Summary: Cognitive dysfunction in Long COVID and ME/CFS was demonstrated using the Stroop task which found global slowing of response times and limitations of practice effects. [ABSTRACT FROM AUTHOR]

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children. [ABSTRACT FROM AUTHOR]

This study identified evidence and considerations for allied health clinicians in providing group interventions for people with cognitive impairment. A scoping review was conducted by searching the MEDLINE (Ovid), CINHAL (EBSCOhost), Scopus (Elsevier), Embase (Ovid) and TROVE databases from 2016. Articles of any study design in which group interventions were performed by an allied health professional with participants with cognitive impairment were included. Data on physical, cognitive, psychological, and quality of life measures were extracted from the selected articles. Standardised mean changes (SMC) were calculated. Ten articles were included in the study. No article directly compared group interventions versus one‐to‐one interventions. The results of the meta‐analysis showed significant improvements after the intervention in the physical (SMC = 0.42, P = 0.013), cognitive (SMC = 0.43, P = 0.005), psychological (SMC = 0.14, P = 0.005), and quality of life domains (SMC = 0.28, P = 0.002). This review identified considerations for clinicians when developing group interventions for people with cognitive impairments, including specific participant criteria, increasing support, modifications to intervention difficulty, and environmental considerations. Group intervention for people with cognitive impairments demonstrated moderate effectiveness in improving physical and cognitive domains and a small effect in improving psychological and quality of life domains. Specific considerations are recommended when clinicians provide group interventions for people with cognitive impairments. [ABSTRACT FROM AUTHOR]

Objective(s): This study aimed to investigate the effect of 8-week high-intensity interval training (HIIT) on lactate-induced mitophagy in the hippocampus of rats with type 2 diabetes. Materials and Methods: 28 Wistar male rats were divided into four groups randomly: (i) control (Co), (ii) exercise (EX), (iii) type 2 diabetes (T2D), and (iv) type 2 diabetes + exercise (T2D + Ex). The rats in the T2D and T2D + Ex groups were fed a high-fat diet for two months, then a single dose of STZ (35 mg/kg) was injected to induce diabetes. The EX and T2D + Ex groups performed 4-10 intervals of treadmill running at 80-100% of Vmax. Serum and hippocampal levels of lactate, as well as hippocampal levels of monocarboxylate transported (MCT2), sirtuin1 (SIRT1), forkhead box protein O (FOXO3), light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin, beta-amyloid (Aβ), hyperphosphorylated tau protein (TAU), Malondialdehyde (MDA), and antioxidant enzymes were measured. One-way ANOVA and Tukey post-hoc tests were used to analyze the data. Results: Serum and hippocampal levels of lactate as well as hippocampal levels of MCT2, SIRT1, FOXO3, LC3, PINK1, Parkin, and antioxidant enzymes were higher while hippocampal levels of Aβ, TAU, and MDA were lower in T2D+EX compared to T2D group (P-value<0.05) Conclusion: HIIT could improve mitophagy through Lactate-SIRT1-FOXO3-PINK1/Parkin signaling in the hippocampus of rats with T2D reducing the accumulation of Tau and Aβ, which may reduce the risk of memory impairments. [ABSTRACT FROM AUTHOR]

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). 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. 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). 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. [ABSTRACT FROM AUTHOR]

Background: The "LIfestyle for BRAin health" (LIBRA) index was recently updated with three new modifiable factors: hearing impairment, social contact, and sleep (LIBRA2), but has not yet been validated. Objective: Comparison of the performance of both LIBRA versions in predicting dementia risk. Methods: Longitudinal data from the English Longitudinal Study of Ageing (ELSA) and the Maastricht Aging Study (MAAS) were used. The weighted LIBRA (11/12 factors available) and LIBRA2 (14/15 factors available) scores were calculated, with higher scores representing an unhealthier lifestyle. Dementia diagnoses were based on self- or informant reported physician diagnosis, an informant-based cognitive screening tool, registry data or test data. Cox-proportional hazards regression was used to investigate the association between LIBRA(2) scores and dementia risk. Model fit and predictive accuracy were determined using the Akaike information criterion and Harrell's C index. Results: Over an average follow-up of 8.3 years in ELSA and 17.9 years in MAAS, 346 (4.6%) and 120 (8.5%) individuals developed dementia, respectively. In ELSA, a one-point increase in LIBRA2 was associated with an 8% (1.06–1.11) higher dementia risk (LIBRA: 13%, 1.09–1.16). In MAAS, a one-point increase in LIBRA2 was associated with a 6% (1.01–1.12) higher dementia risk (LIBRA: 8%, 0.99–1.16). In ELSA, LIBRA (Harrell's C = 0.68) and LIBRA2 (Harrell's C = 0.67) performed similarly. In MAAS, LIBRA2 (Harrell's C = 0.62) performed better compared to LIBRA (Harrell's C = 0.52) Conclusions: LIBRA2 is a better model for identifying individuals at increased dementia risk and for public health initiatives aimed at dementia risk reduction. [ABSTRACT FROM AUTHOR]

Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep‐Sev‐stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)‐dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV‐GFAP‐hM4Di‐eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co‐labelling hippocampal neuronal axon terminals with PSD‐95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep‐Sev‐stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep‐Sev‐stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional‐dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep‐Sev‐stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis‐induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

While many studies have demonstrated a relationship between depression and cognitive deficits, most have neglected to include measurements of performance validity. This study examined the relationship between depression and cognition after accounting for noncredible performance. Participants were veterans referred for outpatient clinical evaluation. The first set of regression analyses (N = 187) included age, sex, and education in Model 1, Beck Depression Inventory-2 (BDI-2) added in Model 2, and pass/failure of Test of Memory Malingering (TOMM) added in Model 3 as predictors of 12 neuropsychological test indices. The second set of analyses (N = 559) mirrored the first but with Major Depressive Disorder (MDD) diagnosis in Models 2 and 3. In the first analyses, after including TOMM in the model, only the relationship between BDI-2 and verbal fluency remained significant, but this did not survive a Bonferroni correction. In the second analyses, after including TOMM and Bonferroni correction, MDD diagnosis was a significant predictor only for CVLT-II Short Delay Free Recall. Therefore, the relationship between depression and cognition may not be driven by frank cognitive impairment, but rather by psychological mechanisms, which has implications for addressing depressed individuals' concerns about their cognitive functioning and suggest the value of providing psychoeducation and reassurance. [ABSTRACT FROM AUTHOR]

Continuous nicotine exposure during adolescence can have profound implications on the development and well-being of individuals in this critical stage of life. As the prevalence of nicotine use among adolescents continues to be a significant public health concern, understanding the impact of this addictive substance on young minds and bodies is crucial. We explored the various dimensions of nicotine exposure in adolescents, from its effects on brain development and cognitive function to the social, emotional, and educational consequences. By looking into the complexities of adolescent nicotine addiction, we can better comprehend the challenges faced by this vulnerable population and develop potential strategies for prevention and intervention. [ABSTRACT FROM AUTHOR]

Summary Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, and disease pathologies. However, the dysregulation of the neuroinflammatory response could significantly affect neurons in terms of function and structure, leading to profound health implications. Although tremendous progress has been made in understanding the relationship between neuroinflammatory processes and alterations in neuronal integrity, the specific implications concerning both structure and function have not been extensively covered, with the exception of perspectives on glial activation and neurodegeneration. Thus, this review aims to provide a comprehensive overview of the multifaceted interactions among neurons and key inflammatory players, exploring mechanisms through which inflammation influences neuronal functionality and structural integrity in the CNS. Further, it will discuss how these inflammatory mechanisms lead to impairment in neuronal functions and architecture and highlight the consequences caused by dysregulated neuronal functions, such as cognitive dysfunction and mood disorders. By integrating insights from recent research findings, this review will enhance our understanding of the neuroinflammatory landscape and set the stage for future interventions that could transform current approaches to preserve neuronal integrity and function in CNS‐related inflammatory conditions. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD).A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis.Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (p = 0.006), GSH (p < 0.001), and Aβ1-42 (p = 0.040) were independent predictors of disease stage. Similarly, UA (p = 0.003), GSH (p < 0.001), and Aβ1-42 (p < 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification.Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD. [ABSTRACT FROM AUTHOR]

Cognitive impairment is frequently seen in patients with type 2 diabetes (T2DM), ranging from mild impairment to dementia. However, our knowledge of the specific profiles and risk factors for these different levels of impairment is limited. In this study involving 152 patients with T2DM, cognitive function was assessed using the Montreal Cognitive Assessment test. The Fuzzy C-means clustering algorithm was utilized to group individuals with similar cognitive characteristics. The study evaluated how well clinical parameters could classify characteristics of clusters using the Classification and Regression Trees algorithm. ROC analysis was then used to assess the classification success. Three distinct cognitive clusters were identified. Cluster 1 had the poorest cognitive performance and was characterized by more women, lower education levels, and lower levels of iron, hemoglobin, and creatine. Cluster 3, the amnestic cluster, was distinguished by low TSH levels. The decision tree model highlighted several parameters, including education level, hemoglobin, duration of diabetes mellitus (DM), iron, TSH, gender, family history of diabetes, and microalbumin/creatinine ratio, as significantly affecting the distinction of cognitive clusters. Diabetes-associated cognitive impairment stems from multifaceted pathophysiological mechanisms influenced by complex risk factors, resulting in diverse types of cognitive deficits. [ABSTRACT FROM AUTHOR]

Background: The number of major operations performed in obese patients is expected to increase given the growing prevalence of obesity. Obesity is a risk factor for a range of postoperative complications including perioperative neurocognitive disorders. However, the mechanisms underlying this vulnerability are not well defined. We hypothesize that obese subjects are more vulnerable to general anaesthesia induced neurotoxicity due to reduced levels of adiponectin. This hypothesis was tested using a murine surgical model in obese and adiponectin knockout mice exposed to the volatile anaesthetic agent sevoflurane. Methods: Obese mice were bred by subjecting C57BL/6 mice to a high fat diet. Cognitive function, neuroinflammatory responses and neuronal degeneration were assessed in both obese and lean mice following exposure to 2 h of sevoflurane to confirm sevoflurane-induced neurotoxicity. Thereafter, to confirm the role of adiponectin deficiency in, adiponectin knockout mice were established and exposed to the sevoflurane. Finally, the neuroprotective effects of adiponectin receptor agonist (AdipoRon) were examined. Results: Sevoflurane triggered significant cognitive dysfunction, neuroinflammatory responses and neuronal degeneration in the obese mice while no significant impact was observed in the lean mice. Similar cognitive dysfunction and neuronal degeneration were also observed in the adiponectin knockout mice after sevoflurane exposure. Administration of AdipoRon partially prevented the deleterious effects of sevoflurane in both obese and adiponectin knockout mice. Conclusions: Our findings demonstrate that obese mice are more susceptible to sevoflurane-induced neurotoxicity and cognitive impairment in which adiponectin deficiency is one of the underlying mechanisms. Treatment with adiponectin receptor agonist ameliorates this vulnerability. These findings may have therapeutic implications in reducing the incidence of anaesthesia related neurotoxicity in obese subjects. [ABSTRACT FROM AUTHOR]

Background: The "LIfestyle for BRAin health" (LIBRA) index was recently updated with three new modifiable factors: hearing impairment, social contact, and sleep (LIBRA2), but has not yet been validated. Objective: Comparison of the performance of both LIBRA versions in predicting dementia risk. Methods: Longitudinal data from the English Longitudinal Study of Ageing (ELSA) and the Maastricht Aging Study (MAAS) were used. The weighted LIBRA (11/12 factors available) and LIBRA2 (14/15 factors available) scores were calculated, with higher scores representing an unhealthier lifestyle. Dementia diagnoses were based on self- or informant reported physician diagnosis, an informant-based cognitive screening tool, registry data or test data. Cox-proportional hazards regression was used to investigate the association between LIBRA(2) scores and dementia risk. Model fit and predictive accuracy were determined using the Akaike information criterion and Harrell's C index. Results: Over an average follow-up of 8.3 years in ELSA and 17.9 years in MAAS, 346 (4.6%) and 120 (8.5%) individuals developed dementia, respectively. In ELSA, a one-point increase in LIBRA2 was associated with an 8% (1.06–1.11) higher dementia risk (LIBRA: 13%, 1.09–1.16). In MAAS, a one-point increase in LIBRA2 was associated with a 6% (1.01–1.12) higher dementia risk (LIBRA: 8%, 0.99–1.16). In ELSA, LIBRA (Harrell's C = 0.68) and LIBRA2 (Harrell's C = 0.67) performed similarly. In MAAS, LIBRA2 (Harrell's C = 0.62) performed better compared to LIBRA (Harrell's C = 0.52) Conclusions: LIBRA2 is a better model for identifying individuals at increased dementia risk and for public health initiatives aimed at dementia risk reduction. [ABSTRACT FROM AUTHOR]

Background: The purpose of this research was to evaluate the efficacy of Narcotrend (NT) monitoring on cognitive dysfunction in patients undergoing anesthesia blockade for gastrointestinal tumors and its effect on cerebral oxygen metabolism and inflammatory response. Methods: Patients preparing to undergo resection of gastrointestinal tumor resection were included and randomly divided into a control group (depth of anesthesia assessed by physician experience) and a research group (depth of anesthesia monitored by NT). HR and MAP were monitored at the preoperatively (T0), 12 h postoperative (T1), 24 h postoperative (T2), and 48 h postoperative (T3) stages. MMSE score was recorded to assess changes in cognitive function. Intracerebral oxygenation indicators (CjvO2, CERO2, and rSO2) were assessed by a blood gas analyzer. ELISA assay was conducted to explore the serum inflammatory indexes (CRP, IL-1β, and TNF-α) and neurological function indicators (NSE and MBP). Results: MAP was higher in the research group than in the control group at T1 and T2 (P < 0.05). MMSE scores at T1, T2, and T3 stages were higher in the research group than in the control (P < 0.05). The incidence of POCD was also lower in the research group compared with the control (P < 0.05). CjvO2, CERO2, and rSO2 were significantly higher (P < 0.05) and were positively correlated with the MMSE scores. Postoperative serum inflammatory indexes were significantly elevated in both groups, but more significantly in the control group (P < 0.05). Both neurological function indicators were usually reduced after surgery, but the reduction was more significant in the research group (P < 0.05). Conclusion: NT monitoring of anesthetic depth has a less physical impact on patients with gastrointestinal tumor anesthetic block, reduces the degree of postoperative POCD, and has significant clinical value. [ABSTRACT FROM AUTHOR]

Cognitive impairment is frequently seen in patients with type 2 diabetes (T2DM), ranging from mild impairment to dementia. However, our knowledge of the specific profiles and risk factors for these different levels of impairment is limited. In this study involving 152 patients with T2DM, cognitive function was assessed using the Montreal Cognitive Assessment test. The Fuzzy C-means clustering algorithm was utilized to group individuals with similar cognitive characteristics. The study evaluated how well clinical parameters could classify characteristics of clusters using the Classification and Regression Trees algorithm. ROC analysis was then used to assess the classification success. Three distinct cognitive clusters were identified. Cluster 1 had the poorest cognitive performance and was characterized by more women, lower education levels, and lower levels of iron, hemoglobin, and creatine. Cluster 3, the amnestic cluster, was distinguished by low TSH levels. The decision tree model highlighted several parameters, including education level, hemoglobin, duration of diabetes mellitus (DM), iron, TSH, gender, family history of diabetes, and microalbumin/creatinine ratio, as significantly affecting the distinction of cognitive clusters. Diabetes-associated cognitive impairment stems from multifaceted pathophysiological mechanisms influenced by complex risk factors, resulting in diverse types of cognitive deficits. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions To evaluate the relationships of cognitive function and care dependency with oral health in a Norwegian older adult population.This cross‐sectional study included 2623 participants aged 70 and older from the fourth wave of the Trøndelag health study (HUNT4 70+) and the city of Trondheim (Trondheim 70+). Neurocognitive disorders (NCDs) were diagnosed by clinical experts according to the DSM‐5 framework. Care dependency referred to nursing home residency. Oral health was assessed by using the Revised Oral Assessment Guide—Jönköping (ROAG‐J). Individuals were considered as ‘having oral problem’ if the score was two or three in at least one of the nine ROAG‐J items. Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs).The prevalence of having oral problems was 19% higher in participants with NCDs than those with normal cognitive function after adjusting for potential confounders (PR 1.19, 95% CI: 1.09–1.29). Further analysis showed a higher prevalence of having oral problems for home dwellers with NCDs (PR 1.23, 95% CI: 1.13–1.33) and nursing home residents (PR 1.32, 95% CI: 1.20–1.45) compared to home dwellers with normal cognitive function.NCDs were associated with an increased prevalence of oral problems in this Norwegian older adult population. The study suggests the need for increasing oral care for home dwellers with NCDs and nursing home residents. [ABSTRACT FROM AUTHOR]

Introduction: Endothelial dysfunction (ED) promotes the development of atherosclerosis, and studies suggest an association with age-related neurocognitive disorders. It is currently unclear whether ED is also associated with the risk of perioperative neurocognitive disorders. Method: We included 788 participants aged ≥ 65 years of the BioCog study. Patients were scheduled to undergo elective surgery with expected duration > 60 min. Blood was collected before surgery for measurement of 5 biomarkers of ED: asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were monitored for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on a battery of 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during the 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. Results: 19.8% of 788 patients developed POD; 10.1% of 537 patients had POCD at 3 months. Concentrations of ED biomarkers were not significantly associated with a POD. A higher VCAM-1 concentration was associated with a reduced POCD risk (adjusted odds ratio 0.55; 95% CI: 0.35–0.86). No further statistically significant results were found. Conclusion: Pre-operative concentrations of ED biomarkers were not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to evaluate these findings. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is a cluster of cardiometabolic conditions that has been linked to high risk for cardiovascular disease, liver complications, and several malignancies. More recently, MetS has been associated with cognitive dysfunction. Summary: Studies have shown an association with minimal cognitive impairment, progression to vascular dementia, and even Alzheimer’s disease. MetS components have been individually explored, and glucose intolerance has the strongest association with impairment in several cognitive domains. Several hypotheses have been proposed regarding the pathophysiology underlying the MetS-cognitive dysfunction association, and even though insulin resistance plays a major role, more studies are needed to elucidate this topic. Moreover, several other factors contributing to this association have been identified. Liver disease and more specifically metabolic dysfunction-associated steatotic liver disease can on its own contribute to cognitive decline through systemic inflammation and higher ammonia levels. Gut dysbiosis that has also been identified in MetS can also lead to cognitive impairment through several mechanisms that result in neurotoxicity. Finally, there are several other factors that may modify the MetS-cognitive dysfunction relationship, such as lifestyle, diet, education status, and age. More recently, circadian syndrome was explored and was found to be even more strongly associated with cognitive impairment. Key Message: MetS is associated with cognitive decline. Certain cardiometabolic risk factors have a stronger association with cognitive impairment, and there are several factors that may modify this relationship. The aim of this review was to assess and summarize the existing body of evidence on the association between MetS and cognitive impairment and identify areas that necessitate further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus Disease-2019 (COVID-19) affects mental health, causing various psychiatric symptoms, including cognitive impairment, which may persist for a long time. To develop effective strategies for combating this global health burden, it is necessary to ascertain whether COVID-19 itself causes cognitive decline or whether other factors also play any role. Aim: To determine the prevalence of cognitive impairment in long COVID patients who present with post-COVID-19 psychiatric sequelae, and to investigate its association with socio-demographic factors, depression, anxiety, and stress. Materials and Methods: A cross-sectional study was conducted from July 2022 to June 2023 at a 'Post-COVID Mental Health Clinic' in a tertiary care medical college in Kolkata, India. A total of 204 subjects were selected through simple random sampling, aged between 18 and 65 years, of both sexes, who had recovered from COVID-19 more than three months but less than six months prior, and who presented with post-COVID-19 psychiatric sequelae, excluding those with a history of psychiatric disease before contracting COVID-19. The dependent variable, cognition, was measured using the Montreal Cognitive Assessment (MoCA) score, while independent variables included socio-demographic factors, depression, anxiety, and stress, measured by the Depression Anxiety Stress Scale-21 (DASS-21) scores. The Chisquare test was used to find the association between cognition and socio-demographic variables and Pearson's correlation test was applied to measure the association of cognition with depression, anxiety, and stress scores. Results: The prevalence of cognitive impairment was found to be 86.8%. Chi-square tests of association showed no significant association with socio-demographic factors. However, there was a significant correlation between the severity of depression (r-value=-0.337, p-value<0.001), anxiety (r-value=-0.275, p-value<0.001), and stress (r-value=-0.277, p-value<0.001) with cognitive impairment. When controlling for anxiety and stress, only depression showed a significant correlation (r-value=-0.221, p-value=0.002). Simple linear regression indicated that the severity of depression significantly predicted the severity of cognitive impairment {R2 =0.114, F(1, 202)=25.88, p-value<0.001}. Conclusion: Cognitive impairment was found to be unrelated to socio-demographic factors, post-COVID-19 anxiety, or stress, except for post-COVID-19 depression, which was identified as a significant predictor of cognitive dysfunction in some patients. This suggests that COVID-19 infection itself may be the most important factor contributing to post-COVID-19 cognitive impairment in patients with post-COVID-19 psychiatric sequelae. [ABSTRACT FROM AUTHOR]

Background There is growing interest in the comorbidity of vascular and neurodegenerative pathologies in patients with cerebrovascular disease (CVD) beyond cerebral amyloid angiopathy (CAA). However, the relationship between amyloid-β and vascular cognitive impairment (VCI) remains debated. Objective To investigate the association between VCI and amyloid-β deposition in non-CAA CVD patients. Methods PubMed, Embase, Web of Science, PsycINFO and CENTRAL databases were systematically searched. Observational studies, including case–control and cohort studies, associating cognitive scores with amyloid load measured by positron emission tomography were selected. Meta-analyses were performed to assess the strength of amyloid–cognition associations across CVD subtypes and cognitive domains. A random-effects model using the inverse variance method was used, with heterogeneity evaluated by Q-statistics and I2 statistics. Meta-regression analyses were conducted to examine the influence of moderators, and publication bias was assessed using funnel plots and Egger's test. All statistical analyses were performed using StataMP 18. Results Twenty-seven eligible studies encompassing 2894 participants were included. Among non-CAA CVD patients, global cognitive performance was significantly lower in those with higher amyloid-β deposition (standardized mean difference = −0.43, P < 0.001). The correlation strength varied across cognitive domains (executive function: r = −0.41; language: r = −0.36; memory: r = −0.29; all P < 0.001). The correlation was significant in patients with subcortical vascular disease (r = −0.43, P < 0.001) but not post-stroke patients (r = −0.19, P > 0.05). Conclusions Amyloid-β load is associated with cognitive decline in non-CAA CVD patients. This is more pronounced in patients with subcortical vascular disease than in post-stroke patients. Executive function is the most susceptible domain in VCI when the level of amyloid-β increases. [ABSTRACT FROM AUTHOR]

Objective: Prior research has underscored the importance of sphingolipid metabolism in Parkinson's disease (PD) pathogenesis. Our objective was to explore the associations between plasma ceramide levels and PD patients with cognitive dysfunction (PD‐CD). Methods: We enrolled two study populations from Eastern China and the Parkinson's Progression Markers Initiative (PPMI), comprising 290 (100 HCs, 160 PDs, and 30 MSAs) and 429 (125 HCs and 304 PDs) participants, respectively. The plasma levels of ceramides (Cer 16:0, Cer 18:0, Cer 24:0, and Cer 24:1) were tested via HPLC–MS/MS analysis. Results: Compared with those in the HC group, the plasma levels of Cer 18:0, Cer 24:1, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were higher in both the PD and MSA groups. Significant differences in the plasma levels of Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were observed among the PD‐NC (PD with normal cognition), PD‐MCI (PD with mild cognitive impairment), and PDD (PD dementia) groups, with the PDD group exhibiting the highest levels. PD patients with higher baseline levels of plasma ceramides (specifically, Cer 18:0, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0) demonstrated accelerated cognitive decline compared with individuals who had lower baseline plasma ceramide levels during the 5‐year follow‐up period. A biomarker panel including Cer 18:0/Cer 24:0 and Cer 24:1/Cer 24:0 could effectively differentiate PD‐CD from PD‐NC with notable diagnostic accuracy. Conclusions: Our results indicate that plasma ceramide levels could potentially be used as diagnostic biomarkers for PD‐CD. [ABSTRACT FROM AUTHOR]

Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic to Brazil, and there is still no specific treatment for these patients. The literature shows that few studies have described the cognitive impairment associated with an HTLV-1 infection, with none of them examining the population of Salvador, where there are approximately forty thousand people infected with the virus. Objectives: To determine the prevalence of cognitive impairment among individuals with HTLV-1. In addition, investigate whether sociodemographic aspects, time since the diagnosis of infection, and the diagnosis of HTLV-Associated Myelopatia/Tropical Spastic Paraparesis (HAM/TSP) or depression are associated with cognitive impairment in this population. Methods: This was an observational, cross-sectional study that consisted of consecutively approaching 100 HTLV-1 patients during outpatient care at a referral center followed by the administration of three questionnaires— the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and Beck's Depression Inventory. Results: The prevalence of cognitive impairment found was 71% using the MMSE and 82% using the MoCA. There was a statistically significant association between the cognitive dysfunction and the variables of age and education according to the MoCA analysis but not the MMSE data. Diagnosis of HAM/TSP was correlated with cognitive impairment using the MMSE but not the MoCA. The prevalence of depression was 20%, and there was no association between cognitive impairment and depressive symptoms in these patients. Conclusions: The findings of this study demonstrate a correlation between cognitive dysfunction and HTVL-1 infection, with a more evident involvement of executive functions and memory. Larger studies are needed to clarify the association between cognitive dysfunction, age, education, and the diagnosis of HAM/TSP. [ABSTRACT FROM AUTHOR]

Objective: Preeclampsia (PE) is associated with hypertension (HTN) during pregnancy and activated CD4+ T cells, inflammatory cytokines, and autoantibodies to the angiotensin II type I receptor (AT1‐AA). Having had COVID‐19 (CV) during pregnancy is associated with an increased incidence of a PE‐like phenotype. Both PE and CV have long‐lasting neurological implications and studies show that nonpregnant COVID patients produce AT1‐AA. We have shown that CD4+ T cells from PE women cause a PE phenotype in nude athymic rats. In this study, we sought to examine the role of CD4+ T cells from PE with a CV History (Hx) to contribute to a PE phenotype and to determine the importance of CD4+ T cells in cognitive dysfunction during pregnancy. Methods: At delivery, blood and placentas were collected, and one million placental CD4+ T cells from each PE and each normotensive patient, with (NT) or without (NP) a CV (Hx) during pregnancy, were isolated, purified, and injected i.p. into a gestational day (GD) 12 pregnant nude athymic rat (one patient/rat). At GD19, blood pressure (MAP) and circulating factors were assessed in recipient rats. Cognitive function and memory were assessed using Novel Object Recognition and Barnes Maze tests, respectively. Placental ACE‐2 activity and AT1‐AA were measured from COVID Hx patients. A one‐ or two‐way ANOVA with Bonferroni's multiple comparisons test was used for statistical analysis. Results: Blood pressure was increased in patients with PE, with or without COVID, compared to NT patients. There were no significant changes in placental ACE activity in patients with COVID Hx with or without PE. AT1‐AA was elevated in PE patients and in both PE and NT COVID Hx compared to control NP. In pregnant recipient rats, MAP increased in CV Hx PE (113 ± 2, n = 8) compared to CV Hx NT (101 ± 5, n = 6). PE and PE CV Hx CD4+ T Cell recipient rats exhibited impaired memory and cognitive dysfunction (p < 0.05), compared to control groups. Recipient rats of PE CV Hx CD4+ T cells had elevated AT1‐AA compared to NT CV Hx recipients. Both COVID Hx groups and recipients of PE CD4+ T cells had elevated TNF alpha compared to NP. Conclusion: Our findings indicate that pregnant patients with a Hx of COVID during pregnancy produce AT1‐AA, with or without PE. Recipients of CD4+ T cells from PE with or without a CV Hx during pregnancy cause HTN and elevated AT1‐AA. TNF‐α is elevated in PE and in CV Hx NT and PE recipients. Interestingly, recipients of T cells from PE patients with or without a Hx of CV had worse cognitive function during pregnancy, compared to recipient rats of NP CD4+ T cells. These data demonstrate the importance of CD4+ T cells in HTN and impaired neurological function during PE in the presence or absence of a prior COVID‐19 infection during pregnancy. [ABSTRACT FROM AUTHOR]

Cortical cerebral microinfarcts (CMIs) are associated with loss of white matter (WM) integrity and cognitive impairment in cross-sectional studies, while further investigation using longitudinal datasets is required. This study aims to establish the association between cortical CMIs and WM integrity assessed by diffusion-tensor imaging (DTI) measures and to investigate whether DTI measures mediate the relationship between cortical CMIs and cognitive decline. Cortical CMIs were graded on 3T MRI. DTI measures were derived from histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA). Cognitive function was assessed using a neuropsychological test battery. Linear mixed-effect models were employed to examine associations of cortical CMIs with longitudinal changes in DTI measures and cognitive function. Final analysis included 231 patients (71.14 ± 7.60 years). Presence of cortical CMIs at baseline was associated with longitudinal changes in MD median and peak height and FA median and peak height, as well as global cognition (β = −0.50, 95%CI: −0.91, −0.09) and executive function (β = −0.77, 95%CI: −1.25, −0.28). MD median mediated the cross-sectional association between cortical CMIs and global cognition. Further studies are required to investigate whether cortical CMIs and loss of WM integrity are causally related or if they are parallel mechanisms that contribute to cognitive decline. [ABSTRACT FROM AUTHOR]

Background: The common illness known as Major depressive disorder (MDD) is defined by significantly increased rates of illness and disease, impairment, and suicidal thoughts. Numerous investigations have demonstrated the significant impact cystatin C plays in cognitive impairment and major depressive disorder (MDD). Aim:Toassess the relation between serum cystatin c concentration and depressive symptoms, suicidal ideation and cognitive dysfunctions in patients with MDD. Methods: this case-control study was carried out on 69 patients with major depressive disorder diagnosed according to DSM-V criteria that attended outpatient clinic of the Psychiatry department El-Azazy psychiatric hospital & Psychiatry department at Zagazig university hospitals and 69 healthy controls. Cystatin C level was measured. Results: Cystatin C level was significantly higher in major depression patients compared to controls. There was a significant positive correlation between cystatin C with age, Hamilton depression rating scale, BECK scale and MOCA scale. Cases in rural areas showed significant elevation in cystatin C level compared to cases in urban areas (p=0.025). There was a significant relation between degree of depression, suicidal ideation, cognitive dysfunction and cystatin C as it was significantly higher in these cases. Cystatin C was a significant predictor of major depressive disorder (AUC=0.851, P value<0.001). The suggested cut-off value (>1 mg/L) showed 66.7% sensitivity, 92.8% specificity, 90.3% PPV and 73.6% NPV Conclusion: Serum Cys C levels are associated with depressive symptoms, cognitive dysfunction and suicidal ideation in MDD patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the mechanism of fisetin inhibiting the activation of microglia NOD-like receptor family protein 3 (NLRP3) inflammasome in microglia and alleviating cognitive impairment after sepsis. Methods C57BL/6 mice were used to establish the sepsis model by cecal ligation and puncture. Mice were divided into four groups: the sham group, the sepsis group, the sepsis+caspase-1 knockout group (sepsis+Cas-1-/- group) and the sepsis+fisetin group. Evans blue was used to detect the permeability of blood-brain barrier (BBB). Morris water maze was used to evaluate the cognitive function of mice. Western blot assay and immunofluorescence double staining were used to detect the expression of NLRP3 inflammasome-related proteins including caspase-1, N-terminal fragment of the GSDMD (GSDMD-N), interleukin (IL)-1β, IL-18 and mitophagy-related proteins (Pink1, Parkin and LC3-Ⅱ) in brain tissue and microglia. Results Compared with the sham group, expression levels of caspase-1, GSDMD-N, IL-1β and IL-18 were significantly increased in the sepsis group (P＜0.05). Compared with the sepsis group, expression levels of caspase-1, GSDMD-N, IL-1β and IL-18 were significantly decreased in the sepsis+Cas-1-/- group (P＜0.05). The expression levels of Pink1, Parkin and LC3- Ⅱ were significantly higher in the sepsis+fisetin group than those of the sepsis group (P＜0.05), and expression levels of caspase-1, GSDMD-N, IL-1β and IL-18 were significantly lower (P＜0.05). After fisetin intervention, the permeability of BBB was decreased and the cognitive impairment (decreased escape latency and increased frequencies of crossing the platform) was alleviated in the sepsis+fisetin group compared with those of the sepsis group (P＜0.05). Conclusion Fisetin may alleviate central inflammation and cognitive impairment after sepsis by inhibiting the activation of microglial NLRP3 inflammasome through activating mitophagy. [ABSTRACT FROM AUTHOR]

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/Aβ42 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/Aβ42 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. [ABSTRACT FROM AUTHOR]

Background: Dementia is a major cause of disability and dependency globally. Mild cognitive impairment (MCI) is considered an early indicator of developing dementia. There are growing efforts to detect and diagnose MCI earlier; consequently, we need to understand the perspectives of individuals and carers regarding the implications of an MCI diagnosis. Objective: To systematically review qualitative literature to understand the impact of a MCI diagnosis on both the individual and their carers, focusing on wellbeing, everyday behaviors, and healthcare utilization. Methods: Key search terms were input into five databases. Studies were included if they were peer-reviewed qualitative research published in English that obtained perspectives of community-dwellers with MCI or carers and focused on either their wellbeing, everyday behaviors and/or healthcare utilization. The protocol was pre-registered on PROSPERO (CRD42021291995). Data was synthesized narratively. Results: Key findings from 15 eligible articles highlighted the negative impact of an MCI diagnosis on the wellbeing of both individuals and carers, due to stigma and limited understanding regarding diagnosis/prognosis. Changes in everyday behavior varied, particularly regarding motivation to engage with physical activity, hobbies and social opportunities. Both individuals and carers were sometimes dissatisfied with healthcare services; ineffective communication during clinical consolations highlighted as a reason for lack of trust in clinicians. Conclusions: Results indicate that an MCI diagnosis impacts both people with MCI and their carers across key facets of life. There is a critical need to effectively communicate the diagnosis and prognosis of MCI to support wellbeing and everyday activities and ensure trust in healthcare services. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation is postulated as a potential mechanism underlying postoperative delirium. This study aimed to investigate the impact of non-steroidal anti- inflammatory drug (NSAID) use on postoperative delirium. Methods: We conducted a literature search in electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, to identify eligible randomized controlled studies. The primary outcome was the incidence of postoperative delirium, and the secondary outcomes included pain scores and the amounts of opioid used at 24 h postoperatively. We estimated the effect size through calculating the odds ratios (ORs) or mean differences (MDs) with 95% CIs, as appropriate. Results: In the analysis of eight studies involving 1,238 participants, the incidence of postoperative delirium was 11% and 19% in the NSAID and control groups, respectively, with a significant reduction in the NSAID group (OR: 0.54, 95% CI [0.38, 0.7], P = 0.0001, I² = 0%). NSAID use had a significant effect on postoperative pain reduction (MD: -0.75, 95% CI [-1.37, -0.13], P = 0.0172, I² = 88%). Significant lower postoperative opioid consumption was observed in the NSAID group (MD: -2.88, 95% CI [-3.54, -2.22], P = 0.0000; I² = 0%). Conclusions: NSAID administration reduced the incidence of postoperative delirium, severity of pain, and opioid dose used. [ABSTRACT FROM AUTHOR]

Postoperative neurocognitive disorders (PoNCDs), such as postoperative delirium and cognitive dysfunction or decline can occur after surgery, especially in older patients. This significantly affects patient morbidity and surgical outcomes. Among various risk factors, recent studies have shown that preoperative frailty is associated with developing these conditions. Although the mechanisms underlying PoNCDs remain unclear, neuroinflammation appears to play an important role in their development. For the prevention and treatment of PoNCDs, medication modification, a balanced diet, and prehabilitation and rehabilitation programs have been suggested. The risk of developing PoNCDs is thought to be lower in ambulatory patients. However, owing to technological advancements, an increasing number of older and sicker patients are undergoing more complex surgeries and are often not closely monitored after discharge. Therefore, equal attention should be paid to all patient populations. This article presents an overview of PoNCDs and highlights issues of particular interest for ambulatory surgery. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim of this study was to examine the discriminative validity of the Brief Assessment of Impaired Cognition (BASIC) case‐finding instrument in a general practice (GP) setting and compare it with other widely used brief cognitive instruments. Methods: Patients aged ≥70 years were prospectively recruited from 14 Danish GP clinics. Participants were classified as having either normal cognition (n = 154) or cognitive impairment (n = 101) based on neuropsychological test performance, reported instrumental activities of daily living, and concern regarding memory decline. Comparisons involved the Mini‐Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Rowland Universal Dementia Assessment Scale (RUDAS), the Mini‐Cog, the 6‐item Clock Drawing Test (CDT‐6) and the BASIC Questionnaire (BASIC‐Q). Results: BASIC demonstrated good overall classification accuracy with an area under the receiver operating characteristic curve (AUC) of 0.88 (95% confidence interval [CI] 0.84–0.92), a sensitivity of 0.72 (95% CI 0.62–0.80) and a specificity of 0.86 (95% CI 0.79–0.91). Pairwise comparisons of the AUCs of BASIC, MMSE, MoCA and RUDAS produced non‐significant results, but BASIC had significantly higher classification accuracy than Mini‐Cog, BASIC‐Q and CDT‐6. Depending on the pretest probability of cognitive impairment, the positive predictive validity of BASIC varied from 0.83 to 0.36, and the negative predictive validity from 0.97 to 0.76. Conclusions: BASIC demonstrated good discriminative validity in a GP setting. The classification accuracy of BASIC is equivalent to more complex, time‐consuming instruments, such as the MMSE, MoCA and RUDAS, and higher than very brief instruments, such as the CDT‐6, Mini‐Cog and BASIC‐Q. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to examine the relationship between excessive daytime sleepiness (EDS) and attention impairment in Chinese individuals with obstructive sleep apnea (OSA). Methods: A total of 1996 OSA patients with an apnea-hypopnea index (AHI) of ≥ 5 events per hour were included in this study. EDS was measured using the Epworth Sleepiness Scale (ESS), while cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Results: OSA patients with EDS demonstrated higher body mass index (BMI), comorbidities of hypertension and diabetes, decreased N3 sleep, increased AHI and ODI, as well as lower minimum oxygen saturation. Despite no significant differences in total cognitive scores assessed by MMSE and MoCA, individuals with comorbid sleepiness exhibited more evident attention deficits in the subdomains of MoCA. Stratified analysis indicated that regardless of age, educational level was the primary factor influencing attention in the AHI < =20 group. In the AHI > 20 group, attention impairment in patients younger than 40 remained significantly associated with education level, whereas for individuals aged 40 and above, attention deficits were associated with education level, age, and daytime sleepiness. The interaction analysis indicated that OSA severity modulated the impact of sleepiness on attention in patients aged 40 and above. Conclusion: A significant correlation was observed between EDS and attention deficits in Chinese individuals diagnosed with OSA, with a particular emphasis on patients aged 40 and above. The severity of OSA modulates the impact of sleepiness on attention in patients aged 40 and above. [ABSTRACT FROM AUTHOR]

Previous studies have confirmed that irisin is released during and after exercise, a subset of physical activity. However, the association between incidental physical activity, including walking up the stairs or to the bus stop, and irisin levels in adults remains unclear. We investigated the association between incidental physical activity and circulating irisin levels in adults. We searched PubMed and Web of Science databases from inception to March 1, 2023. Studies investigating the association between physical activity (but not exercise) and irisin levels in adults were included. Subgroup and meta-regression analyses were performed to identify the factors that could modify the association between physical activity and irisin. The primary outcome was the standardized mean difference (SMD) in circulating irisin levels between the least and most active groups. Twenty articles were included in this systematic review, totaling 6881 adults. Adults engaging in physical activity showed a higher circulating irisin concentration than inactive counterparts (SMD: 1.56; 95%CI: 1.49, 1.63; I2 = 99.1%). Meta-regression revealed that the SMD between active and inactive adults was lower in women than men. Sporadic physical activity is positively associated with circulating irisin levels in adults. [ABSTRACT FROM AUTHOR]

Objective(s): Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism. Materials and Methods: Wistar rats were orally administered 50% ethanol for 10 weeks, followed by treatment with HGD at doses of 16, 32, or 64 mg/kg/day for an additional 6 weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap1, Nrf-2, HO-1, and NQO-1 were tested by PCR and western blot. Results: Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-1, Occludin, and Claudin-5. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-1β, IL-6, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-2, HO-1, and NQO-1 while down-regulating Keap1 expression. Conclusion: These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction. [ABSTRACT FROM AUTHOR]

The effect of lifestyle factors on cognitive function related to four major noncommunicable diseases (NCDs) including diabetes, cardiovascular disease, cancer, and chronic respiratory diseases, and the relationship between these NCDs and cognitive function have not been fully studied. We aimed to investigate the longitudinal associations between these NCDs and cognitive function in middle-aged and older people, and the combined effects of lifestyle factors. By employing the data from three large-scale cohort studies from the U.S. Health and Retirement Study (2010–2019), English Longitudinal Study of Aging (2014–2019), and China Health and Retirement Longitudinal Study (2011–2019), this study carried out a multi-cohort analysis to 77, 210 participants. Fixed-effects regression models were used to examine associations between NCD status and cognitive function. Margin plots were used to illustrate the effect of lifestyle factors. Our findings revealed the dose-dependent association between mounting these NCDs and declining cognitive performance, ranging from one NCD (β = −0.05, 95 % CI: −0.08 to −0.02) to four NCDs (β = −0.51, 95 % CI: −0.75 to −0.28). Decline in cognitive function associated with NCDs was exacerbated with physical inactivity, current smoking status, and an increase in unhealthy lifestyle behaviors. The observational study design precludes causal interrogation of lifestyles and four NCDs on cognitive function. An increasing number of these NCDs were dose-dependently associated with the decline in cognitive function score. Unhealthy lifestyle factors expedite decline in cognitive function linked to these NCDs. • Rise in 4 major NCDs and decline in cognitive function alarms health. • More NCDs dose-dependently associated with lower cognitive function scores. • Unhealthy lifestyle factors expedite decline in NCD-linked cognitive function. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional study aims to analyze the differences in gut flora between patients with epilepsy with and without cognitive impairment and normal subjects. Methods: One hundred patients with epilepsy who came to our hospital from 2020.12 to 2022.12 (epilepsy group) were selected, and another 100 family members of the patients were selected as the control group (control group). Patients with epilepsy were further classified by the MMSE scale into 62 patients with combined cognitive impairment (Yes group) and 38 patients without cognitive impairment (No group). Detection of gut flora in feces by 16 S rRNA high-throughput sequencing. Logistic regression was used to analyze risk factors for cognitive dysfunction in patients with epilepsy. Results: There were more significant differences in the structure and composition of the gut flora between patients in the epilepsy group and the control group, but no significant differences in diversity analysis (P > 0.05). Actinobacteriota, Faecalibacterium and Collinsella were significantly lower in the Yes group than in the No group (P < 0.05), and the Alpha diversity index was numerically slightly smaller than in the No group, with the PCoA analysis demonstrating a more dispersed situation in both groups. Five metabolic pathways, including glycolysis and heterolactic fermentation, were upregulated in the Yes group. LEfSe analysis showed that five groups of bacteria, including Coriobacteriaceae and Collinsella, were selected as marker species for the presence or absence of comorbid cognitive impairment. Of these, Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy combined with cognitive impairment. Conclusion: There was an imbalance in the gut flora of patients with epilepsy compared to healthy controls. The gut flora of patients with epilepsy with cognitive dysfunction differs significantly from that of patients without cognitive dysfunction. Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy with cognitive dysfunction and can be used as an indicator for the observation of epilepsy with cognitive dysfunction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a disabling disease of the central nervous system. People living with MS often have co-existing sleep disorders and cognitive dysfunction. The objective of this study was to scrutinize the relationship between cognitive outcomes and sleep conditions in MS. Methods: This study followed the Joanna Briggs Institute's (JBI) and PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science databases were searched and original studies delineating the relationship between sleep status and cognitive findings in MS patients‌ were included. The risk of bias was assessed using the JBI critical appraisal tools. Results: In the final review, out of 1635 screened records, 35 studies with 5321 participants were included. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and polysomnography were the most common assessment tools for evaluation of sleep condition, and cognitive evaluations were conducted using the tests including Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test (BVMT). Assessing the quality of studies showed no significant bias in most of the included articles. A link between sleep condition and cognitive abilities was suggested in the literature, especially with objective measurement of sleep condition; however, current evidence did not support a substantial association between self-reported sleep quality and processing speed and working memory in patients with MS. Discussion: Evidence proposes sleep is an independent factor associated with cognitive outcomes in MS. Given the limitations of the evidence such as the lack of well-designed prospective studies, these findings need to be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background/Objectives: Population aging poses many challenges to public health, highlighting loneliness and social isolation as severe problems that affect the physical and mental health of older adults. During the COVID-19 pandemic, these became aggravated. The objective of the present study was to assess the prevalence of loneliness and its relationship with social isolation, depression, cognitive deterioration, sleep quality, and the level of physical mobility and functioning of older adults in Health Area 3 of the Region of Murcia. Methods: A descriptive, observational, and cross-sectional study was performed. The inclusion criteria were age ≥ 65, living in Health Area 3 of the Region of Murcia, and not being institutionalized. The following variables were evaluated: sociodemographic variables, loneliness (UCLA scale), social isolation (DUFSS), depression (GDS), cognitive deterioration (Pfeiffer), sleep quality (PSQI), and mobility (Barthel index). A univariate and multivariate regression model was created to examine how the dependent variable was related to the independent variables. Results: A total of 102 older adults participated in the study. Of these, 31.4% perceived unwanted loneliness and 14.7% low social support. The multivariate regression analysis showed that social isolation, geriatric depression, and cognitive deterioration were significant predictors of loneliness. Conclusions: The findings highlight the importance of developing multifaceted interventions that address not only social isolation but also other interrelated factors such as depression, cognitive deterioration, and sleep quality. The strategies should be centered on community programs and support networks. It is fundamental to perform longitudinal studies to better understand the causal relationships between these variables. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. The prevalence of both AF and dementia is steadily rising and is expected to rise further in the coming decades. There is increasing evidence to suggest an association between AF and various degrees of cognitive dysfunction, from mild cognitive impairment to severe dementia. In this review, we aimed to discuss the epidemiological aspects, pathophysiological mechanisms, role of neuroimaging, impact of treatment modalities, and clinical and socioeconomic impact of this association. Numerous observational studies and meta-analyses have revealed this association to exist in AF patients with and without a history of stroke, and the association also persists after adjusting for shared risk factors such as hypertension and diabetes mellitus. Various pathophysiological mechanisms have been proposed for this association, including silent cerebral infarcts, cerebral microbleeds, cerebral hypoperfusion, inflammation, and atherosclerosis. While neuroimaging findings have been utilized to suggest some of these pathophysiological mechanisms, more studies are needed to further elucidate this and to determine the potential role of neuroimaging in altering anticoagulation and other treatment decisions. Anticoagulants have shown effectiveness in reducing the rate of cognitive decline in AF patients; however, their role in low-risk AF patients remains under investigation. Even though AF patients receiving catheter ablation may have post-operative cognitive dysfunction in the short term, long-term follow-up studies have shown an improvement in cognitive function following ablation. Cognitive decline in AF patients often occurs with greater functional decline and other psychosocial impairments such as depression and anxiety and future research on this association must incorporate aspects of social determinants of health and associated outcomes. [ABSTRACT FROM AUTHOR]

AbstractWith an aging population, detecting cognitive dysfunction at an early stage is important. However, no current neurophysiological assessments examine brain activity status in community-dwelling older adults. Therefore, this study aimed to characterize event-related potential (ERP) during go/no-go tasks in older adults with potential cognitive impairment living in the community. The participants were 34 young adults and 46 older adults. They underwent a go/no-go task to measure ERP. The older adults were divided into two groups for analysis based on the results of the Japanese version of the Montreal Cognitive Assessment (MoCA-J): cognitively normal and cognitively impaired. N2 latency was significantly delayed in the cognitively impaired group compared to the cognitively normal and younger groups. Furthermore, the younger group exhibited a significant increase in P3 amplitude and shorter latency compared to both older adult groups. The results of the correlation analysis between ERP and neuropsychological test scores showed that N2 latency correlated with neuropsychological test scores. The results also suggested that receiver operating characteristic curve analysis can measure cognitive function. These results indicated that N2 latency reflected potential cognitive dysfunction in community-dwelling older adults. Furthermore, P3 amplitude may be useful in detecting age-related inhibitory function decline. [ABSTRACT FROM AUTHOR]

Sepsis‐associated encephalopathy (SAE) occurs in 70% of severely infected patients and the incidence rate of 17.7%. Previous studies have shown that Nicotinamide adenine dinucleotide (NADH) may treat nerve damage, but its inability to directly penetrate cell membranes limits its application. In this study, a nanoparticle (NADH@HMONs‐AAL) with one modification of triple‐role nano‐therapy is creatively prepared to treat SAE, and it is delivered to the brain through intranasal administration. There are three‐fold to introduce aleuria aurantia lectin (AAL) to modify the surface of NADH@HMONs. First, AAL adhered to HMONs as a mesoporous blocker to prevent drug leakage. Then, AAL increases the hydrophilic and hydrophobic properties of the nanoparticles, making NADH@HMONs more easily enter cells. Third, AAL allowed NADH@HMONs to bind to L‐fucose residues expressed on the olfactory epithelium, reducing clearance by cilia and effectively transporting NADH@HMONs‐AAL to the brain. This research indicates that NADH@HMONs‐AAL can directly enter the brain through intranasal administration and rapidly release NADH within cells. It repairs neuronal damage in the hippocampus and improves cognitive dysfunction in SAE‐induced cognitive neuroinflammatory mice. In conclusion, the nanoparticle prepared in this study using precision can alleviate the cognitive dysfunction caused by SAE, and provide a promising delivery route and method for treating neurological diseases. [ABSTRACT FROM AUTHOR]

Sepsis-associated encephalopathy (SAE) is a critical neurological complication of sepsis and represents a crucial factor contributing to high mortality and adverse prognosis in septic patients. This study explored the contribution of NAT10-mediated messenger RNA (mRNA) acetylation in cognitive dysfunction associated with SAE, utilizing a cecal ligation and puncture (CLP)-induced SAE mouse model. Our findings demonstrate that CLP significantly upregulates NAT10 expression and mRNA acetylation in the excitatory neurons of the hippocampal dentate gyrus (DG). Notably, neuronal-specific Nat10 knockdown improved cognitive function in septic mice, highlighting its critical role in SAE. Proteomic analysis, RNA immunoprecipitation, and real-time qPCR identified GABABR1 as a key downstream target of NAT10. Nat10 deletion reduced GABABR1 expression, and subsequently weakened inhibitory postsynaptic currents in hippocampal DG neurons. Further analysis revealed that microglia activation and the release of inflammatory mediators lead to the increased NAT10 expression in neurons. Microglia depletion with PLX3397 effectively reduced NAT10 and GABABR1 expression in neurons, and ameliorated cognitive dysfunction induced by SAE. In summary, our findings revealed that after CLP, NAT10 in hippocampal DG neurons promotes GABABR1 expression through mRNA acetylation, leading to cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate cognitive functions of patients with psoriasis in terms of subclinical neurological involvement using p300 method, and to reveal the correlation between the disease duration and severity if any. Methods: 40 patients with psoriasis vulgaris and 40 healthy individuals were included in the study. Standard mini mental test and beck depression inventory were applied to the groups. PASI values and DLQI values of psoriasis patients were calculated. P300 measurements of both groups were recorded and assessed in order to evaluate the cognitive functions. Results: There was no statistically significant difference between the healthy and psoriasis groups in terms of PzLat, PzAmp, CzLat and CzAmp values (p=0.681, p=0.301, p=0.138, p=0.739, respectively). When it was compared in terms of PASI values, there was no statistically significant difference in the patient group in terms of PzLat, PzAmp, CzLat and CzAmp values (p=0.211, p=0.422, p=0.106, p=0.305, respectively). When evaluated according to disease duration, there was no statistically significant difference between the groups in terms of PzLat, PzAmp, CzLat and CzAmp values (p=0.901, p=0.244, p=0.632, p=0.868, respectively). Conclusion: Cognitive functions in psoriasis patients are not affected by the presence, severity and duration of the disease. As far as we know, the present study is the first study using electrophysiological P300 method in evaluating the cognitive functions in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Aims: Emerging evidence suggests that cerebral small vessel disease (CSVD) pathology changes brain structural connectivity (SC) and functional connectivity (FC) networks. Although network‐level SC and FC are closely coupled in the healthy population, how SC‐FC coupling correlates with neurocognitive outcomes in patients with different CSVD burdens remains largely unknown. Methods: Using multimodal MRI, we reconstructed whole‐brain SC and FC networks for 54 patients with severe CSVD burden (CSVD‐s), 106 patients with mild CSVD burden (CSVD‐m), and 79 healthy controls. We then investigated the aberrant SC‐FC coupling and functional network topology in CSVD and their correlations with cognitive dysfunction. Results: Compared with controls, the CSVD‐m patients showed no significant change in any SC‐FC coupling, but the CSVD‐s patients exhibited significantly decreased whole‐brain (p = 0.014), auditory/motor (p = 0.033), and limbic modular (p = 0.011) SC‐FC coupling. For functional network topology, despite no change in global efficiency, CSVD‐s patients exhibited significantly reduced nodal efficiency of the bilateral amygdala (p = 0.024 and 0.035) and heschl gyrus (p = 0.001 and 0.005). Notably, for the CSVD‐s patients, whole‐brain SC‐FC coupling showed a significantly positive correlation with MoCA (r = 0.327, p = 0.020) and SDMT (r = 0.373, p = 0.008) scores, limbic/subcortical modular SC‐FC coupling showed a negative correlation (r = −0.316, p = 0.025) with SCWT score, and global/local efficiency (r = 0.367, p = 0.009 and r = 0.353, p = 0.012) showed a positive correlation with AVLT score. For the CSVD‐m group, whole‐brain and auditory/motor modular SC‐FC couplings showed significantly positive correlations with SCWT (r = 0.217, p = 0.028 and r = 0.219, p = 0.027) and TMT (r = 0.324, p = 0.001 and r = 0.245, p = 0.013) scores, and global/local efficiency showed positive correlations with AVLT (r = 0.230, p = 0.020 and r = 0.248, p = 0.012) and SDMT (r = 0.263, p = 0.008 and r = 0.263, p = 0.007) scores. Conclusion: Our findings demonstrated that decreased whole‐brain and module‐dependent SC‐FC coupling associated with reduced functional efficiency might underlie more severe burden and worse cognitive decline in CSVD. SC‐FC coupling might serve as a more sensitive neuroimaging biomarker of CSVD burden and provided new insights into the pathophysiologic mechanisms of clinical development of CSVD. [ABSTRACT FROM AUTHOR]

Agastache rugosa, a traditional Asian herbal medicine, is primarily used for digestive problems; yet, its cognitive benefits remain unexplored. This study evaluated the anti-amnesic effects of A. rugosa extract (ARE) on scopolamine (SCO)-induced memory impairment in mice. Mice received 100 or 200 mg/kg ARE orally for 5 days, followed by SCO injection. The ARE demonstrated significant antioxidant (DPPH IC50: 75.3 µg/mL) and anti-inflammatory effects (NO reduction). Furthermore, the ARE significantly improved memory performance in the passive avoidance test (escape latency: 157.2 s vs. 536.9 s), the novel object recognition test (novel object preference: 47.6% vs. 66.3%) and the Morris water maze (time spent in the target quadrant: 30.0% vs. 45.1%). The ARE reduced hippocampal acetylcholinesterase activity (1.8-fold vs. 1.1-fold) while increasing choline acetyltransferase (0.4-fold vs. 1.0-fold) and muscarinic acetylcholine receptor subtype I (0.3-fold vs. 1.6-fold) expression. The ARE improved hippocampal neurogenesis via doublecortin- (0.4-fold vs. 1.1-fold) and KI-67-positive (6.3 vs. 12.0) cells. Therefore, the ARE exerts protective effects against cognitive decline through cholinergic system modulation and antioxidant activity, supporting its potential use as a cognitive enhancer. [ABSTRACT FROM AUTHOR]