Cognitive Damage Research Articles

Factors associated with older adults' cognitive decline 6 months after gamma-variant SARS-CoV-2 infection.

Cognitive deficits are commonly reported after COVID-19 recovery, but little is known in the older population. This study aims to investigate possible cognitive damage in older adults 6 months after contracting COVID-19, as well as individual risk factors. This cross-sectional study involved 70 participants aged 60-78 with COVID-19 6 months prior and 153 healthy controls. Montreal Cognitive Assessment-Basic (MoCA-B) screened for cognitive impairment; Geriatric Depression Scale and Geriatric Anxiety Inventory screened for depression and anxiety. Data were collected on demographics and self-reports of comorbid conditions. The mean age of participants was 66.97 ± 4.64 years. A higher proportion of individuals in the COVID group complained about cognitive deficits (χ2 = 3.574; p = 0.029) and presented with deficient MoCA-B scores (χ2 = 6.098, p = 0.014) compared to controls. After controlling for multiple variables, all the following factors resulted in greater odds of a deficient MoCA-B: COVID-19 6-months prior (OR, 2.44; p = 0.018), age (OR, 1.15; p < 0.001), lower income (OR, 0.36; p = 0.070), and overweight (OR, 2.83; p = 0.013). Further analysis pointed to individual characteristics in COVID-19-affected patients that could explain the severity of the cognitive decline: age (p = 0.015), lower income (p < 0.001), anxiety (p = 0.049), ageusia (p = 0.054), overweight (p < 0.001), and absence of cognitively stimulating activities (p = 0.062). Our study highlights a profile of cognitive risk aggravation over aging after COVID-19 infection, which is likely mitigated by wealth but worsened in the presence of overweight. Ageusia at the time of acute COVID-19, anxiety, being overweight, and absence of routine intellectual activities are risk factors for more prominent cognitive decline among those infected by COVID-19.

Cognitive Reserve in Parkinson's Disease without Dementia: β-Amyloid and Metabolic Assessment.

Cognitive reserve (CR) is the mismatch between preserved cognition and neuropathological damage. Amyloidopathy in Parkinson's disease (PD) could be associated with faster progression to dementia, but the putative protective effect of CR is unknown. To evaluate the effect of CR on β-amyloid burden and brain metabolism in non-demented PD subjects. Participants with PD (n = 53) underwent a clinical evaluation, [18 F]-fluorodeoxyglucose and [18 F]-flutemetamol positron emission tomography magnetic resonances, and were classified according to CR. The metabolic pattern of 16 controls was compared to PD subjects. The PD subjects showed hypometabolism mainly in the bilateral posterior cortex. Superior-CR subjects (n = 22) exhibited better cognitive performance, increased amyloid burden, and higher metabolism in several right hemisphere areas compared to low-medium-CR subjects (n = 31). Higher CR in non-demented PD is associated with better cognitive performance, which might reduce vulnerability to the effect of β-amyloid. Whether superior CR leads to protection against metabolic deterioration, and predominantly right hemisphere involvement, deserves further exploration.

A Biopsychosocial Approach to Persistent Post-COVID-19 Fatigue and Cognitive Complaints: Results of the Prospective Multicenter NeNeSCo Study

ObjectiveTo evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints. DesignProspective, multicenter cohort study. SettingSix Dutch hospitals. Participants205 initially hospitalized (March-June 2020), confirmed patients with SARS-CoV-2, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, magnetic resonance imaging (MRI) contraindication, or severe neurologic damage post-hospital discharge (N=205). InterventionsNot applicable. Main Outcome MeasuresNine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from medical dossiers. Hierarchical regression analyses were performed on fatigue severity (Fatigue Severity Scale; FSS) and cognitive complaints (Cognitive Consequences after Intensive Care Admission; CLC-IC; dichotomized into CLC-high/low). Variable blocks: (1) Demographic and premorbid factors (sex, age, education, comorbidities), (2) Illness severity (ICU/general ward, PROMIS physical functioning [PROMIS-PF]), (3) Neuro-cognitive factors (self-reported neurological symptoms, MRI abnormalities, cognitive performance), (4) Psychological and social factors (Hospital Anxiety and Depression Scale [HADS], Utrecht Coping List, Social Support List), and (5) Fatigue or cognitive complaints. ResultsThe final models explained 60% (FSS) and 48% (CLC-IC) variance, with most blocks (except neuro-cognitive factors for FSS) significantly contributing. Psychological and social factors accounted for 5% (FSS) and 11% (CLC-IC) unique variance. Higher FSS scores were associated with younger age (P=.01), lower PROMIS-PF (P<.001), higher HADS-Depression (P=.03), and CLC-high (P=.04). Greater odds of CLC-high were observed in individuals perceiving more social support (OR=1.07, P<.05). ConclusionsResults show that psychological and social factors add to biomedical factors in explaining persistent post-COVID-19 fatigue and cognitive complaints. Objective neuro-cognitive factors were not associated with symptoms. Findings highlight the importance of multidomain treatment, including psychosocial care, which may not target biologically-rooted symptoms directly but may reduce associated distress.

Comparing the Effectiveness of Mindfulness-based Stress Reduction Training and Powell’s Cognitive Rehabilitation on Improving the Quality of Life of Stroke Patients

Background: Stroke is a type of neurological disorder that can be attributed to a central vascular cause. Stroke can affect the patient’s performance in daily activities and quality of life (QoL). Research indicates a decrease in the quality of life in stroke patients due to cognitive and emotional damage. Objectives: The present study compared the effect of two group approaches, mindfulness training based on stress reduction and Powell’s cognitive rehabilitation, on improving the quality of life of stroke patients. Methods: This semi-experimental study used a pretest-posttest design with a control group and a follow-up period. The sample consisted of 36 eligible stroke patients selected in a targeted and simple random manner. The patients were divided into two intervention groups and one control group. The tools used were a demographic information questionnaire and a Stroke-specific QoL (SS-QOL) scale. Data were analyzed with SPSS software (version. 26). Chi-square, repeated measures analysis of variance, and Bonferroni statistical tests were applied at a significance level of P 0.05). The mindfulness intervention had a higher effect on quality of life on average. Still, statistically, none of the interventions were effective in improving quality of life (P &gt; 0.05), and there was no significant difference between the effect of mindfulness-based methods and cognitive rehabilitation on improving quality of life (P &gt; 0.05). Conclusions: Mindfulness training increases behavioral responses related to attention as the basis of all cognitive activities. Also, mindfulness exercises improve cognitive skills and, by affecting the cognitive system, increase the capacity and ability of the information processing system and improve the quality of life.

Therapeutic Effects of the major alkaloid constituents of Evodia rutaecarpa in Alzheimer's disease.

Since the report of Alzheimer's disease (AD) in 1907, it has garnered widespread attention due to its intricate pathogenic mechanisms, significant impact on patients' lives, and the substantial burden it places on society. Presently, effective treatments for AD remain elusive. Recent pharmacological studies on the traditional East Asian herb, Evodia rutaecarpa, have revealed that the bioactive alkaloid components within it can ameliorate AD-related cognitive impairments and neurological damage through various pathways, including anti-inflammatory, antioxidant, and anti-acetylcholinesterase activities. Consequently, this article provides an overview of the pharmacological effects and research status of the four main alkaloid components found in Evodia concerning AD. We hope this article will serve as a valuable reference for experimental and clinical research on the use of Evodia in AD prevention and treatment.

The impact of burn injury on the central nervous system.

Burn injuries can be devastating, with life-long impacts including an increased risk of hospitalization for a wide range of secondary morbidities. One area that remains not fully understood is the impact of burn trauma on the central nervous system (CNS). This review will outline the current findings on the physiological impact that burns have on the CNS and how this may contribute to the development of neural comorbidities including mental health conditions. This review highlights the damaging effects caused by burn injuries on the CNS, characterized by changes to metabolism, molecular damage to cells and their organelles, and disturbance to sensory, motor and cognitive functions in the CNS. This damage is likely initiated by the inflammatory response that accompanies burn injury, and it is often long-lasting. Treatments used to relieve the symptoms of damage to the CNS due to burn injury often target inflammatory pathways. However, there are non-invasive treatments for burn patients that target the functional and cognitive damage caused by the burn, including transcranial magnetic stimulation and virtual reality. Future research should focus on understanding the mechanisms that underpin the impact of a burn injury on the CNS, burn severity thresholds required to inflict damage to the CNS, and acute and long-term therapies to ameliorate deleterious CNS changes after a burn.

Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice.

The aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/min, 5 Gy*2) total body irradiation. The behavior and activity of mice were assessed 60 days after ionizing radiation (IR) exposure. After that, the pathological changes and mechanism of the mouse brain and femoral tissues were observed by HE, Nissl, Trap staining micro-CT scanning and RNA sequencing (RNA-Seq), and Western blot. The results show that singular or fractional IR exposure led to a decrease in spatial memory ability and activity in mice, and the cognitive and motor functions gradually recovered after singular 5 Gy IR in a time-dependent manner, while the fractional 10 Gy IR group could not recover. The decrease in bone density due to the increase in osteoclast number may be relative to the down-regulation of RUNX2, sclerostin, and beta-catenin. Meanwhile, the brain injury caused by IR exposure is mainly linked to the down-regulation of BNDF and Tau. IR exposure leads to memory impairment, reduced activity, and self-recovery, which are associated with time and dose. The mechanism of cognitive and activity damage was mainly related to oxidative stress and apoptosis induced by DNA damage. The damage caused by fractional 10 Gy TBI is relatively stable and can be used as a stable multi-organ injury model for radiation mechanism research and anti-radiation medicine screening.

Association between erythrocyte membrane fatty acids and gut bacteria in obesity-related cognitive dysfunction

Obesity increases the risk of cognitive impairment and dementia, and the gut microbiota can affect brain cognitive function and obesity through a variety of pathways such as the gut-brain axis. This study aimed to discover how fatty acid affect cognitive function by regulating intestinal flora in obesity. Obese subjects were recruited for cognitive function assessment, and participants were divided into obese group with cognitive impairment (MCI, n = 49) and obese cognitively normal group (Non_MCI, n = 55). In the erythrocyte membrane, the proportion of polyunsaturated fatty acids (PUFA), linoleic acid (C18:2 n-6) and arachidonic acid (C20:4 n-6) and n-6/n-3 ratio was higher in the MCI group than in the Non_MCI group. However, the α-linolenic acid (C18:3 n-3) percentage of the erythrocyte membrane was lower in the MCI group. We found that Coriobacteriales_Incertae_Sedis was positively correlated with erythrocyte membrane C20:4 n-6 and n-6 PUFA and negatively correlated with cognitive scores in obese patients. In addition, several of the functional pathways we predicted were significantly different in the MCI and Non_MCI groups. Higher levels of n-6/n-3 polyunsaturated fatty acids ratio in the erythrocyte membranes may influence the inflammatory response in the organism causing obesity induced cognitive damage. Moreover, high levels of n-6/n-3 polyunsaturated fatty acids ratio may also affect the intestinal flora of obese patients, which in turn may affect the cognitive function of obese patients.

Efficacy of enhanced extracorporeal counterpulsation combined with atorvastatin in the treatment of cognitive impairment after stroke.

Cerebral apoplexy patients are prone to cognitive impairment, and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke. To evaluate the effects of enhanced external counterpulsation (EECP) in conjunction with atorvastatin on cognitive function, neurotransmitter levels, and the repair of brain tissue damage in patients with cognitive impairment due to stroke. In this retrospective study, data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group (n = 30) and a control group (n = 30) according to the different nursing methods applied. Patients in the treatment group received EECP in addition to atorvastatin, while those in the control group received atorvastatin alone. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and activities of daily living (ADL) scale scores were compared between the two groups. Additionally, the two groups were compared in terms of serum acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), endothelin-1 (ET-1), β2-microglobulin (β2-MG), glial fibrillary acidic protein (GFAP), and visinin-like protein 1 (VILIP-1) in the serum. Blood flow measurements from the anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA) were compared between the two groups before and after treatment, and the pulsatility index (PI) and resistance index (RI) of each artery were determined. MMSE, MoCA, and ADL scores all improved in both groups following treatment, with the study group showing more improvement than the control group (P < 0.05). After treatment, there were statistically significant increases in both ACh and NO levels, whereas decreases occurred in AChE, ET-1, β2-MG, VILIP-1, and GFAP, levels and the PI and RI of the left-ACA, right-ACA, left-MCA, right-MCA, left-PCA, and right-PCA. The study group showed greater gains in all metrics than the control group (P < 0.05). EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function, neurotransmitter levels, and brain tissue damage status of patients.

Modification of the height of a weight drop traumatic brain injury model that causes the formation of glial scar and cognitive impairment in rats

ObjectiveTraumatic brain injury (TBI) is a chronic, progressive condition associated with permanent disabilities, particularly cognitive impairments. Glial scar formation following TBI is considered a contributing factor to these persistent disabilities. Currently, limited research exists on pharmacological interventions targeting glial scar prevention that require a standard weight drop TBI model for glial scar formation. Since there is no established standard TBI model for glial scar formation, this study aims to validate and modify the height of the weight drop model to identify glial scar formation and cognitive impairments.MethodsFifteen male Sprague Dawley rats were randomly divided into sham, WD1, and WD2 groups. The weight drop model with a 10 g load was applied to the right exposed brain of the rats from a height of 5 cm (WD1) and 10 cm (WD2) using a modified Feeney’s weight drop device. Cognitive impairments were confirmed using the novel object recognition (NOR) test with ethovision software on day 15. Subsequently, the rats were decapitated on day 16, and GFAP immunohistochemical staining was performed to confirm the presence of glial scarring.ResultsThe WD1 and WD2 groups exhibited a significant increase in glial scar formation compared to the sham group, with the WD2 group resulting in even more pronounced glial scar formation. Only the WD2 model caused statistically significant cognitive damage. The negative correlation coefficient indicates that an increase in GFAP + cells will decrease the cognitive function.ConclusionModification of the height of the weight drop model, by dropping a weight of 10 g from a height of 10 cm (WD2 group) onto the right brain exposed of the rat has been proven to induce the formation of a glial scar and cognitive impairment.

Effects of Metformin Administration on Behavioral and Biochemical Parameters in a Familial Hypercholesterolemia Mouse Model

AbstractBackgroundLow‐density lipoprotein (LDL) is responsible for the transport of cholesterol to peripheric tissues (Cortes et al. 2014), and it enters the cells via LDL receptors (LDLr) (Luo, Yang, Song 2020). Cholesterol metabolism alterations, i.e., hypercholesterolemia are well‐known cardiovascular risk factors and have also been linked to cognitive and behavioral alterations (De Oliveira et al. 2011, Sparks et al. 1990, WHO 2008). Familial hypercholesterolemia (FH) is a prevalent disease caused by dysfunctions of cholesterol metabolism (Akioyamen et al. 2017), and several reports show its connection to neuroinflammation (Ariza et al. 2016, De Oliveira et al. 2020). Recent studies associate mTOR inhibition with conservation of blood‐brain barrier integrity, cognitive damage attenuation, and systemic and cerebral inflammation reduction in dementia and FH animal models (Jahrling et al. 2018, Van Skike et al. 2018). In this regard, Metformin presents critical therapeutic potential because it inhibits mTOR through AMPK.ObjectiveEvaluation of Metformin treatment on cognitive disturbances and central and peripheric biochemical parameters in C57BL/6 LDLr deficient (LDLr‐/‐) mice.MethodLDLr‐/‐ and wild‐type (WT) male mice (3‐month‐old, 20‐3 g) received a daily oral administration via gavage of Metformin (200 mg/kg) or Saline for 30 days. All animals were weighed weekly. Mice were submitted to behavioral tasks in the last week of treatment. Following the last day of treatment, animals fasted for 12 hours and were euthanized by cardiac exsanguination. Heparinized plasma was used to determine total cholesterol and triglyceride levels. Another cohort of animals was perfused with paraformaldehyde to collect fixed total brains, which were used in immunofluorescence assays for labeling glial fibrillary acidic protein (GFAP).ResultLDLr‐/‐ mice showed higher total cholesterol levels compared to WT groups. Metformin treatment increased triglyceride levels and decreased total body weight in LDLr‐/‐ mice in comparison to Saline administration. LDLr‐/‐ mice showed hyperlocomotive activity, cognitive damage, and a depressed phenotype, which was in parts attenuated by Metformin treatment. Metformin treatment ameliorated astrogliosis in the hippocampus of LDLr‐/‐ mice.ConclusionMetformin treatment showed a promising effect on the memory impairment and astrocyte reactivity observed in LDLr‐/‐ mice, which was not via a cholesterol‐lowering outcome.

The circulating sclerostin as a biomarker for brain white matter damage in hemodialysis patients

AbstractBackgroundPatients with kidney disease, especially those receiving hemodialysis, presented a higher risk of cognitive impairment and brain white matter damage than those without kidney disease. Previous research suggests an association between lower bone marrow densities and cognitive impairments. However, the study investigating the relationship between bone turnover biomarkers and brain white matter damage in hemodialysis patients is sparse.MethodsThe enrolled hemodialysis participants were examed on the Fazekas scale of brain magnetic resonance imaging (MRI) white matter lesions and measured 8 bone turnover proteins using the Luminex bead‐based multiplex assay. The Fazekas scale of periventricular lesions was from grade 0 to grade 3. Multivariable ordinal regression and logistic regression models were examined to determine the independent relationship between bone turnover proteins and the Fazekas scale of periventricular lesions.ResultsIn 59 hemodialysis patients, older patients had more periventricular lesions on the Fazekas scale, which was connected with a worse Mini‐Mental State Examination score (MMSE). The serum level of sclerostin, one of eight bone turnover proteins, displayed a dose‐response relationship (P value for trend = 0.004), meaning that a greater sclerostin level was connected with a lower grade on the Fazekas scale. Both the ordinal regression model (odds ratio [OR] 0.886; 95% confidence interval [CI] 0.828‐0.947, P value 0.001) and the logistic regression model (odds ratio [OR] 0.828; 95% 0.712‐0.963, P value = 0.014) determined a negative association between sclerostin and the Fazekas scale of periventricular lesions after complete adjustment for potential confounders.ConclusionsThe brain white matter damage was inversely correlated with the level of circulating sclerostin. Our finding suggested a possible connection between bone turnover proteins and brain damage.

Survival and pharmacotherapy delay in young onset Alzheimer’s disease

AbstractIntroductionSpecific feature of young onset Alzheimer’s disease (YOAD) patients is that their diagnosis and therefore their treatment is usually delayed. Firstly, they present atypically, secondly, they have a higher cognitive reserve and symptoms are later recognized and finally at that age, the family, and the patients themselves, do not think about the possibility of dementia, which prolongs the time period to seeking medical help (on average 2‐3 years).AimTo examine the association of survival in YOAD with time elapsed from the onset of symptoms to the initiation of pharmacotherapy.Material and methodsThis is a retrospective study on 135 patients from Memory Center of Neurology Clinic, Clinical Center of Serbia, with clinical diagnosis of YOAD. We included outpatients that had first visit to our clinic from 01.04.2012. do 01.04.2017. The association of survival with time elapsed from onset of symptoms to initiation of therapy was examined by Kaplan Meier survival analysis with log rank test.ResultsFrom 2012, when the registry was created, till 2019, 89 out of 135 included patients died. Kaplan Meier survival analysis showed that patients with lower MMSE score (from 15 points and below) and who could not dress themselves or perform personal hygiene at the time of inclusion in our registry have a shorter expected survival than those who had MMSE 16 and above (p = 0.019) and who functioned independently in terms of these activities of daily living (p = 0.041 for dressing and p = 0.018 for performing personal hygiene). Patients in whom the introduction of therapy was delayed 3 or less years survived for a year longer than patients in whom therapy was introduced 4 or more years after the onset of dementia symptoms (p = 0.004).ConclusionOur study clearly showed that certain clinical parameters (degree of cognitive and functional damage at the time of therapy introduction), but also delay in introducing therapy from symptoms onset determine the length of survival in YOAD.

The Beneficial Effects of C-peptide for Diabetic Encephalopathy

Diabetes is a disease that millions of people globally are affected by its symptoms along with its complications. Even with treatment plans such as insulin injections or pumps, diabetes remains a widescale, worldwide problem. If a patient is diagnosed with diabetes, they can experience heart and kidney disease, vision dysfunction, oral health deterioration, and nerve damage. However, as recent studies show, a peptide, which was originally used as an early detection tool for diabetes, has exhibited many remunerative characteristics that may benefit diabetes and other complications caused by the disease. More specifically, diabetic encephalopathy, a disease known for cognitive impairment and damage to the nervous system, could improve with the help of C-peptide. With C-peptide’s therapeutic effects of improved blood flow, nerve cell regeneration and repair, anti-inflammatory responses, and a decrease in experiencing a stroke, C-peptide has many profitable advantages for treating complications of diabetes related to the deterioration of the nervous system. In this study, the paper will discuss the latest findings on the effects of C-peptide on diabetic encephalopathy, the disadvantages and limits with the use of the substance, areas of uncertainty, and how the new discovery may alter the future. Researchers hope with this new discovery there will be further research done to figure out how C-peptide may help other diseases in the body or may act as a potential cure for diabetes. C-peptide may become a more common and effective candidate for treatment options of diabetes.

Terapi Seni (Mewarnai dan Menggambar) Membantu Lansia Mengatasi Kecemasan

Psychological disorders in the elderly include dementia, anxiety, sleep disturbances and depression. Anxiety is the most common disorder. Based on data from the Ministry of Health, emotional disorders in the elderly in Indonesia occur 10% in the age range 65-74 years and 13% occur in elderly people aged more than 75 years. Elderly people who experience anxiety need good treatment to reduce their anxiety, otherwise it can cause cognitive damage and depression. Handling to reduce anxiety experienced by providing activities that are positive, interesting and fun. One of them is with art therapy. This study aims to determine the effect of coloring therapy on the anxiety level of the elderly. The sample in this study was 30 people who were taken by purposive sampling. The research design used is descriptive analytic with a quasi-experimental approach. The data analysis test used was univariate, bivariate with paired t-test for the effect of art therapy (coloring and drawing)intervention on the anxiety level of the elderly. The results of the study showed that there was a significant difference in the average anxiety score of the elderly before and after the therapeutic intervention (p value = 0.003) with a difference in the average value decreasing the mean score = 5.03, in addition there was a decrease in the moderate and severe anxiety categories between before and after the intervention. Conclusion: coloring and drawing therapy helps reduce anxiety levels in the elderly.

Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults, characterized by primary and secondary injury. Primary injury is the immediate mechanical damage, while secondary injury results from delayed neuronal death, often linked to mitochondrial damage accumulation. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential treatment for modulating secondary post-traumatic neuronal death. However, the specific molecular mechanism by which HBOT modulates secondary brain damage through mitochondrial protection remains unclear. Spatial learning, reference memory, and motor performance were measured in rats before and after Controlled Cortical Impact (CCI) injury. The HBOT (2.5 ATA) was performed 4 h following the CCI and twice daily (12 h intervals) for four consecutive days. Mitochondrial functions were assessed via high-resolution respirometry on day 5 following CCI. Moreover, IHC was performed at the end of the experiment to evaluate cortical apoptosis, neuronal survival, and glial activation. The current result indicates that HBOT exhibits a multi-level neuroprotective effect. Thus, we found that HBOT prevents cortical neuronal loss, reduces the apoptosis marker (cleaved-Caspase3), and modulates glial cell proliferation. Furthermore, HBO treatment prevents the reduction in mitochondrial respiration, including non-phosphorylation state, oxidative phosphorylation, and electron transfer capacity. Additionally, a superior motor and spatial learning performance level was observed in the CCI group treated with HBO compared to the CCI group. In conclusion, our findings demonstrate that HBOT during the critical period following the TBI improves cognitive and motor damage via regulating glial proliferation apoptosis and protecting mitochondrial function, consequently preventing cortex neuronal loss.

Pseudoginsenoside GQ mitigates chronic intermittent hypoxia-induced cognitive damage by modulating microglia polarization

Obstructive sleep apnea (OSA), a state of sleep disruption, is characterized by recurrent apnea, chronic intermittent hypoxia (CIH) and hypercapnia. Previous studies have showed that CIH-induced neuroinflammatory plays a crucial role in cognitive deficits. Pseudoginsenoside GQ (PGQ) is a new oxytetracycline-type saponin formed by the oxidation and cyclization of the 20(S) Rg3 side chain. Rg3 has been found to afford anti-inflammatory effects, while whether PGQ plays a role of anti-neuroinflammatory remains unclear. The purpose of this study was to investigate whether PGQ attenuates CIH-induced neuroinflammatory and cognitive impairment and the possible mechanism it involves. We found that PGQ significantly ameliorated CIH-induced spatial learning deficits, and inhibited microglial activation, pro-inflammatory cytokine release, and neuronal apoptosis in the hippocampus of CIH mice. In addition, PGQ pretreatment promoted microglial M1 to M2 phenotypic transition in IH-induced BV-2 microglial, as well as indirectly inhibited IH-induced neuronal injury via modulation of microglia polarization. Furthermore, we noted that activation of HMGB1/TLR4/NF-κB signaling pathway induced by IH was inhibited by PGQ. Molecular docking results revealed that PGQ could bind to the active sites of HMGB1 and TLR4. Taken together, this work supports that PGQ inhibits M1 microglial polarization via the HMGB1/TLR4/NF-κB signaling pathway, and indirectly exerts neuroprotective effects, suggesting that PGQ may be a potential therapeutic strategy for cognitive impairment accompanied OSA.

PPARα agonist fenofibrate prevents postoperative cognitive dysfunction by enhancing fatty acid oxidation in mice.

Due to high rates of incidence and disability, postoperative cognitive dysfunction (POCD) currently receives a lot of clinical attention. Disturbance of fatty acid oxidation is a potential pathophysiological manifestation underlying POCD. Peroxisome proliferator-activated receptor α (PPARα) is a significant transcription factor of fatty acid oxidation that facilitates the transfer of fatty acids into the mitochondria for oxidation. The potential role of PPARα intervention in POCD warrants consideration. The present study is aimed to investigate whether PPARα agonist fenofibrate (FF) could protect long-term isoflurane anesthesia-induced POCD model and to explore the potential underlying function of fatty acid oxidation in the process. We established the POCD model via 6 h long-term isoflurane anesthesia in vivo with C57BL/6J mice and in vitro with N2a cells. Cells and mice were pretreated with PPARα agonist FF before anesthesia, after which fatty acid oxidation and cognitive function were assessed. The level of fatty acid oxidation-related proteins was determined using western blotting. The contextual fear conditioning test was utilized to evaluate mice's learning and memory. Our results showed that 6 h long-term isoflurane anesthesia induced contextual memory damage in mice, accompanied by decreases of fatty acid oxidation-related proteins (peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1A, and PPARα) both in the hippocampus of POCD mice and in N2a cells. In the N2a cell model, pretreatment of PPARα agonist FF led to the upregulation of fatty acid oxidation-related proteins. In vivo results showed that preconditioned FF reached similar effects. More crucially, FF has been shown to reduce cognitive damage in mice after long-term isoflurane anesthesia. Additionally, our data showed that after blocking fatty acid oxidation by Etomoxir, FF failed to protect cognitive function from long-term isoflurane anesthesia. Pretreatment of PPARα agonist FF can protect against long-term isoflurane anesthesia-induced POCD by enhancing fatty acid oxidation.

Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity.

Neurodegenerative diseases (NDs) are characterized by a progressive deterioration of neuronal function, leading to motor and cognitive damage in patients. Astrocytes are essential for maintaining brain homeostasis, and their functional impairment is increasingly recognized as central to the etiology of various NDs. Such impairment can be induced by toxic insults with palmitic acid (PA), a common fatty acid, that disrupts autophagy, increases reactive oxygen species, and triggers inflammation. Although the effects of PA on astrocytes have been addressed, most aspects of the dynamics of this fatty acid remain unknown. Additionally, there is still no model that satisfactorily explains how astroglia goes from being neuroprotective to neurotoxic. Current incomplete knowledge needs to be improved by the growing field of non-coding RNAs (ncRNAs), which is proven to be related to NDs, where the complexity of the interactions among these molecules and how they control other RNA expressions need to be addressed. In the present study, we present an extensive competing endogenous RNA (ceRNA) network using transcriptomic data from normal human astrocyte (NHA) cells exposed to PA lipotoxic conditions and experimentally validated data on ncRNA interaction. The obtained network contains 7 lncRNA transcripts, 38 miRNAs, and 239 mRNAs that showed enrichment in ND-related processes, such as fatty acid metabolism and biosynthesis, FoxO and TGF-β signaling pathways, prion diseases, apoptosis, and immune-related pathways. In addition, the transcriptomic profile was used to propose 22 potential key controllers lncRNA/miRNA/mRNA axes in ND mechanisms. The relevance of five of these axes was corroborated by the miRNA expression data obtained in other studies. MEG3 (ENST00000398461)/hsa-let-7d-5p/ATF6B axis showed importance in Parkinson's and late Alzheimer's diseases, while AC092687.3/hsa-let-7e-5p/[SREBF2, FNIP1, PMAIP1] and SDCBP2-AS1 (ENST00000446423)/hsa-miR-101-3p/MAPK6 axes are probably related to Alzheimer's disease development and pathology. The presented network and axes will help to understand the PA-induced mechanisms in astrocytes, leading to protection or injury in the CNS under lipotoxic conditions as part of the intricated cellular regulation influencing the pathology of different NDs. Furthermore, the five corroborated axes could be considered study targets for new pharmacologic treatments or as possible diagnostic molecules, contributing to improving the quality of life of millions worldwide.

Quantitative estimate of cognitive resilience and its medical and genetic associations

BackgroundWe have proposed that cognitive resilience (CR) counteracts brain damage from Alzheimer’s disease (AD) or AD-related dementias such that older individuals who harbor neurodegenerative disease burden sufficient to cause dementia remain cognitively normal. However, CR traditionally is considered a binary trait, capturing only the most extreme examples, and is often inconsistently defined.MethodsThis study addressed existing discrepancies and shortcomings of the current CR definition by proposing a framework for defining CR as a continuous variable for each neuropsychological test. The linear equations clarified CR’s relationship to closely related terms, including cognitive function, reserve, compensation, and damage. Primarily, resilience is defined as a function of cognitive performance and damage from neuropathologic damage. As such, the study utilized data from 844 individuals (age = 79 ± 12, 44% female) in the National Alzheimer’s Coordinating Center cohort that met our inclusion criteria of comprehensive lesion rankings for 17 neuropathologic features and complete neuropsychological test results. Machine learning models and GWAS then were used to identify medical and genetic factors that are associated with CR.ResultsCR varied across five cognitive assessments and was greater in female participants, associated with longer survival, and weakly associated with educational attainment or APOE ε4 allele. In contrast, damage was strongly associated with APOE ε4 allele (P value < 0.0001). Major predictors of CR were cardiovascular health and social interactions, as well as the absence of behavioral symptoms.ConclusionsOur framework explicitly decoupled the effects of CR from neuropathologic damage. Characterizations and genetic association study of these two components suggest that the underlying CR mechanism has minimal overlap with the disease mechanism. Moreover, the identified medical features associated with CR suggest modifiable features to counteract clinical expression of damage and maintain cognitive function in older individuals.