Impaired Cognitive Function Research Articles

Non-adherence to antidementia medications and associated factors: a study of Spanish population-based registry data

IntroductionWith an increasing prevalence, dementia is one of the most disabling diseases among the elderly. Impaired cognitive function and behavioral and psychological symptoms predispose patients to medication non-adherence, resulting in increased morbidity, mortality, and healthcare costs. The aim of this study was to estimate the prevalence of non-adherence to antidementia medications and to identify the main predictors.MethodsA population-based registry study was conducted in 2022 in Castile and Leon, Spain. A total of 17,563 patients with dementia were included. The medication possession ratio (MPR) was used as an indirect method to measure adherence. The cut-off point for determining that a patient was nonadherent was 80% of MPR. Multivariate logistic regression was used to identify predictors of nonadherence based on sociodemographic and health-related variables.ResultsIn 2022, 6.2% of the population over 80 years old used antidementia medications. Of these patients, 70% were women, 28.15% were institutionalized, and over 90% were polymedicated and had multiple prescribers. The most used medicines were donepezil (43.49%), rivastigmine (36.84%), and memantine (30.7%). The combined use of an acetylcholinesterase inhibitor plus memantine was relevant (13.33%). Men were less adherent than women, and the prevalence of non-adherence decreased with age. The medication associated with the highest prevalence of non-adherence was rivastigmine (19%), followed by donepezil (17%) and memantine (13.23%). Institutionalized patients (13%) and patients on combination therapy (13.29%) had the lowest prevalence of non-adherence. Protective factors against non-adherence include institutionalization, polymedication, use of memantine or combination therapy, and comorbid mental illness.ConclusionsIn Castile and Leon, one in six patients were non-adherent to antidementia medications. Younger male patients with cardiometabolic disease are more likely to be non-adherent to antidementia medications. On the other hand, institutionalization is a protective factor against non-adherence, but still 10% of nursing home patients are non-adherent to antidementia medications.

Behavioural profiling following acute stress uncovers associations with future stress sensitivity and past childhood abuse.

Background: Individuals greatly differ in their responses to acute stress, ranging from resilience to vulnerability that may yield stress-related psychopathology. Stress-related psychopathologies involve, by definition, substantial modifications across multiple behavioural domains, including impaired cognitive, affective and social functioning. Nevertheless, and despite extensive investigation of individual variability in stress responsivity, no study to date simultaneously assessed the impact of acute stress across multiple behavioural domains within a given individual.Objective: To address this critical gap, 84 healthy female participants (mean age 24.45 ± 3.02, range 19-35) underwent an established acute stress induction procedure and completed three behavioural tasks, probing the functional domains of positive, cognitive and social processing, both before and after the acute stress procedure.Method: A novel behavioural profiling algorithm was implemented to identify individuals whose performance was substantially impacted by stress across all three functional domains.Results: Approximately 30% of participants exhibited substantial deviation in their performance from before to after stress in all three tasks, hereon defined as stress-affected. Stress-affected participants did not differ in their psychological and physiological responses to the acute stress procedure from the other stress-unaffected 70% of the sample. However, follow-up assessments in 66 of these participants revealed higher levels of stress six months following the procedure among the stress-affected compared to the stress-unaffected group. Stress-affected individuals also reported more aversive childhood experiences, such that the odds of participants who were sexually abused at an early age to be affected behaviourally by acute stress later in life increased by more than five-fold.Conclusions: Taken together, these findings suggest that being affected by acute stress across multiple functional domains is associated with future stress sensitivity and past childhood sexual abuse. Probing individual differences in the impact of acute stress across domains of functionality may better align with the multi-dimensional nature of stress responsivity, uncovering latent vulnerability.

Plasma neurofilament light chain in fibromyalgia: A case control study exploring correlation with clinical and cognitive features.

Plasma neurofilament light chain (NFL) has been measured as a biomarker of neuronal damage in various neurological disorders. Elevated tau and β-amyloid levels have been found in patients with fibromyalgia (FM). The aim of the present study was to compare plasma neurofilament levels in fibromyalgia patients with normal controls and to investigate the correlation with clinical features and cognitive tests. Plasma NFL levels were assessed in 33 FM patients and compared with 22 age-matched controls. All patients were also assessed with clinical scales examining fibromyalgia disability, sleep quality and duration, fatigue, anxiety, and depression, and a neuropsychological battery examining executive function, verbal short-term memory, and working memory, as well as attentional executive function and selective attention, interference sensitivity, and inhibition of automatic responses. NFL levels were higher in FM patients (controls 6.19± 1.92; FM 17.28± 15.94 pg/mL ANOVA p 0.002). Working memory was the most impaired cognitive function significantly correlated with high NFL scores (Pearson p 0.034). Short sleep times also correlated with higher NFL scores (Pearson p 0.02) and poorer working memory performance (Pearson p 0.02). No correlation was found with indices of disease severity and duration. Plasma NFL levels are elevated in fibromyalgia patients, suggesting neuronal damage and correlating with a slight decrease in working memory and short sleep duration. Plasma neurofilament levels are elevated in patients with fibromyalgia, regardless of disease severity and duration. Neurofilament levels are higher in patients with mild working memory impairment and sleep disorders. Subgroups of patients with primary neuronal damage phenomena could be individualized for prospective evaluation with regard to the possible development of cognitive decline and sleep disturbances, which would justify a tailored therapeutic approach.

Features of Brain Damage after Neutron Irradiation of the Head and Modification of the Damage by Lactoferrin.

: Mouse heads were irradiated in a beam of neutrons and gamma rays from the IR-8 nuclear reactor. The brain cells of control and irradiated mice were isolated using Percoll. Neurons and resting and activated microglial cells were analyzed using the fluorescently labeled antibodies and flow cytometry. The level of DNA double-strand breaks in neurons was determined by γH2AX histone content. Cytokine gene expression in the hippocampus was studied by RT-PCR. Behavior and cognitive functions were studied using the open field, Morris water maze, and novel object recognition tests. LF was isolated from female colostrum by preparative ion-exchange chromatography and purified by affinity chromatography on heparin-Sepharose. : γ,n-Irradiation of the mouse head at a dose of 1.5 Gy led to an increase in the level of DNA double-strand breaks in neurons. Twenty-four hours after irradiation the total number of cells and the number of neurons in the isolated fraction of brain cells decreased, but the number of microglial cells remained unchanged. The number of resting and activated microglia did not change within 3-72 h after γ,n-irradiation. The expression level of the TNFα, IL-1β, and IL-6 genes increased 2 months after γ,n-irradiation of the mouse head at a dose of 1.5 Gy, indicating the development of neuroinflammation. At this time, irradiated mice demonstrated the anxiety-like behavior and impaired spatial and episodic memory. A single i.p. administration of human LF to mice immediately after γ,n-irradiation of the head did not affect the observed radiation-induced disturbances, but decreased the gene expression levels of TNFα, IL-1β, and IL-6 pro-inflammatory cytokines and increased the gene expression level of TGFβ anti-inflammatory cytokine in the hippocampus 2 months after radiation exposure. The obtained results indicate a partial decrease in the level of hippocampal neuroinflammation of irradiated animals treated with LF. . γ,n-Irradiation of the mouse head at a dose of 1.5 Gy leads to DNA damage of neurons and the decrease in the number of neurons. Microglia cells are more resistant to such radiation exposure. Late after head-only γ,n-irradiation, mice develop neuroinflammation, which is detected by an increase in the pro-inflammatory cytokine gene expression in the hippocampus and also by anxiety-like behavior and impaired cognitive functions. A single LF administration leads to a partial decrease in the neuroinflammation level, but does not affect the other studied parameters. The optimal dosing regimen of LF remains to be determined to preserve cognitive functions after γ,n-irradiation of the brain.

Recombinant human plasma gelsolin suppresses persistent neuroinflammation and restores hippocampal neurogenesis in murine model of decompression sickness.

Loss of plasma gelsolin (pGSN), a protein that lyses actin filaments, is implicated in the pathology of inflammatory and neurodegenerative diseases. We hypothesized that because pGSN is depleted in a murine model of decompression sickness (DCS), supplementation by administration of human recombinant (rhu-) pGSN would ameliorate inflammatory events. We observed that pGSN levels were persistently decreased in mice for at least 12 days post-exposure to 790 kPa of air for 2 hours. This decline was associated with elevated levels of inflammatory microparticles (MPs) in the blood and cervical lymph nodes, which previously were shown to cause neuroinflammation. Additionally, these mice exhibited reduced expression of synaptic proteins, impaired neurogenesis as well as impaired cognitive and motor functions. Rhu-pGSN ameliorated the inflammatory changes and resulted in restored synaptic protein expression, neurogenesis and neurological function. These findings demonstrate that neuronal dysfunction in our murine model of DCS is mediated by MPs and that rhu-pGSN can ameliorate injury even when administered in a delayed fashion.

Attention as the dimension that deteriorates first in patients with cognitive impairment after myocardial infarction

Abstract Background Previous publications by our team indicated a high prevalence (approximately 35%) of cognitive impairment (CI) in patients after myocardial infarction (MI). Moreover, we observed that the presence of peri-infarction deficits was not always associated with their occurrence after 6 months of follow-up and vice versa. This was the basis for distinguishing 4 groups of patients: a) group 1 – CI present peri-infarction and after 6 months; b) group 2 – CI present only peri-infarction; c) group 3 – CI present only after 6 months; d) group 4 – no CI during the study. Purpose The aim of the current study is to analyse the type of CI in patients after MI with a focus on its changes within the 4 groups mentioned. Methods The study included 326 patients hospitalised for MI treated by percutaneous coronary intervention. Cognitive function was assessed twice using the Mini–Mental State Examination (MMSE) and the Clock Drawing Test (CDT)-Shulman version during the first hospitalisation (on day 2-3 after MI) and 6 months later. In addition, the occurrence of sleep, aggression and mood disorders was assessed. The constructed research model was analysed with artificial intelligence algorithms. Results Persistent CI (group1) was found in 8.9%, peri-infarct CI (group 2) in 16.3%, and only after 6 months (group 3) in 7.7% of study participants (as assessed by MMSE). Analysis of the cognitive domains showed that in those who improve (group 2) or worsen cognitive function (group 3), analogous changes in attention function occurred, respectively improving in 81% and worsening in 100% of subjects in a given group. It was observed that there is a group of patients with a CI on the MMSE who perform CDT correctly, 12% peri-infarct and 11% at 6-month follow-up, respectively. Patients with a normal CDT score but CIs found in the MMSE have impaired attentional function regardless of the time of assessment. Conclusion CIs can occur both immediately after MI and during subsequent follow-up. However, after 6 months of intensive anti-atherosclerotic treatment (post-MI), cognitive functions improve in some patients, and deteriorate in others. At the same time, the cognitive function that undergoes similar changes in these groups is attention. The uniform type of impaired cognitive function and the lack of specific differences between the 4 groups allow us to assume a uniform etiology of cognitive deficits. Patients with normal CDT and disorders present in MMSE show deficits in attention functions. Performing CDT and using the MMSE component assessing attention function could prove sufficient for the initial assessment of cognitive functions in the population of patients after MI. The results require confirmation in a larger patient population.

The association between preserved ratio impaired spirometry (PRISm) and cognitive function among American older adults: the mediating role of systolic blood pressure

BackgroundRecent studies have drawn attention to the association between preserved ratio impaired spirometry (PRISm) and cognitive function decline. High systolic blood pressure (SBP) is a known risk factor for both PRISm and dementia. This study aimed to investigate whether elevated SBP may mediate the relationship between PRISm and cognitive function in older adults.MethodsThis study analyzed 732 participants aged ≥ 60 years who had completed spirometry and cognitive function tests in the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Multivariable linear regression was employed to assess the relationship between PRISm and cognitive function, as measured through the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning sub-test, the Animal Fluency test (AFT), the Digit Symbol Substitution test (DSST), and global cognition tests. All cognitive tests were modeled as z-scores, and global cognition was calculated as the sum of the z-scores of the CERAD, AFT, and DSST. Mediation analyses were conducted to test the mediating effect of SBP on the association between PRISm and cognitive function.ResultsParticipants with PRISm had lower AFT (β = -0.300; 95% confidence interval [CI] = -0.479 to -0.122; p = 0.001), DSST (β = -0.157; 95% CI = -0.309 to -0.004; p = 0.044), and global cognition scores (β = -0.211; 95% CI = -0.369 to -0.053; p = 0.009) than those with normal spirometry, after adjusting for all potential confounders. SBP was considerably associated with AFT (β = -0.084; 95% CI = -0.162 to -0.005; p = 0.038) and DSST (β = -0.132; 95% CI = -0.207 to -0.057; p < 0.001), mediating 7.9% and 18.0% of the association of PRISm with cognitive function, respectively. Furthermore, SBP mediated 17.1% of the association of PRISm with global cognition.ConclusionsThe findings suggested the potential role of SBP as a mediator of associations between PRISm and cognitive decline in older adults.

Exploring alterations of gut/blood microbes in addressing iron overload-induced gut dysbiosis and cognitive impairment in thalassemia patients

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients.

Atlas-Based Structural Disconnectomes Are Associated with Cognitive Performance in Brain Tumors.

Background: Brain tumors are associated with impaired cognitive functioning, which may result from disruptions in brain structural connectivity. Estimating structural disconnections is a more advantageous representation of tumor impact and can be performed indirectly through normative brain atlases. Materials and Methods: Using a publicly available dataset of glioma and meningioma patient MRI scans and tumor masks, latent correlations were estimated between measures of structural disconnection and attention-based cognitive functioning. These measures included gray matter (GM) parcel damage, white matter tract damage, GM parcel-to-parcel disconnections, and reaction time (RTI) as part of the Cambridge Neuropsychological Test Automated Battery to assess attention. Results: Preprocessing pipelines with two different methods of minimizing the pathology impact on MRI normalization were utilized: cost-function masking and lesion filling. The results across both pipelines were nearly consistent, with significant correlations mainly found between RTI measures and the damage to the left inferior fronto-occipital and uncinate fasciculus, as well as the left prefrontal-visual disconnections. Conclusions: This alludes to the importance of left-hemispheric prefrontal-visual coupling in attention-based tasks, particularly those involving object- and feature-based attention.

Ictal and interictal epileptic networks of 34 patients with Hypothalamic Hamartoma on scalp electroencephalography.

To investigate ictal and interictal cortical involvement in epilepsy associated with hypothalamic hamartoma. We conducted a retrospective study of 34 patients with epilepsy and hypothalamic hamartoma, using data from long-term video-EEG-monitoring. We analyzed onset and propagation of ictal and interictal scalp EEG and visualized the resulting networks of cortical involvement. According to clinical and EEG criteria we grouped patients in: (1) focal disease, (2) focal advanced disease, (3) extended disease. We compared networks between these groups and different seizure types. Eight patients underwent several video-EEGs, and we analyzed all to investigate epilepsy progression. Epileptic activity mainly involved frontal and temporal cortex regions. Involvement of frontal regions was more common in advanced stages of the disease, and strong fronto-temporal connections were observed in the ictal networks of patients in intermediate stages (25.0% (left) and 35.7% (right) of seizures with EEG correlate). Occurrence and timing of EEG-correlate significantly depended on the seizure type (Chi-2-test, p<<0.001). In patients with several EEGs, seizure activity increased by +0.67 seizures/day/month (mean). There were significant differences between patients with normal and impaired cognitive function, with the latter showing pronounced ictal involvement of fronto-temporal cortex areas (p<0.001). Overall, in epilepsy due to hypothalamic hamartoma, cortical involvement focuses on frontal and temporal regions and varies systematically with the stage of the disease, different seizure types and presence of impaired cognitive function. We propose that these data may help improve our general understanding of epileptogenesis and potentially provide insights for the surgical therapy of hypothalamic hamartomas.

Relationship between hearing impairment and dementia and cognitive function: a Mendelian randomization study

BackgroundThere is a substantial body of observational research indicating an association between hearing impairment and dementia, yet the causal relationship and underlying mechanisms remain uncertain. This study aims to investigate the causal relationship between hearing impairment and its subtypes with dementia and cognitive function using two-sample Mendelian randomization (MR) analysis.MethodsWe performed two-sample MR analysis to examine the causal effects of hearing impairment and its subtypes, including conductive and sensorineural hearing loss (CSHL), conductive hearing loss (CHL), sensorineural hearing loss (SHL), and sudden sensorineural hearing loss (SIHL), on six dementia phenotypes (overall dementia, Alzheimer’s disease [AD], Lewy body dementia [DLB], frontotemporal dementia [FTD], Parkinson’s disease dementia, and vascular dementia) and four cognitive functions. Additionally, multivariable MR (MVMR) analysis was employed to investigate potential mediating mechanisms.ResultsGenetically determined CSHL was associated with an elevated risk of DLB (odds ratio [OR] 1.69; 95% CI 1.08 to 2.63; P = 0.021) and FTD (OR 1.66; 1.04 to 2.67; P = 0.035), but not AD (P = 0.958). Genetic predisposition to CHL was found to link with increased risks of AD (OR 1.07; 1.01 to 1.14; P = 0.031). Genetically determined SHL was causally associated with an elevated risk of semantic dementia (OR 3.81; 1.09 to 13.37; P = 0.037). Genetically predicted CHL and SIHL were both causally associated with lower general cognitive performance (β -0.015 and − 0.043; P = 0.007 and 0.013) and fluid intelligence score (β -0.045 and − 0.095; P = 0.037 and 0.040). In MVMR analysis, the causal relationship between hearing impairment and dementia was mediated by loneliness, depressed mood, and brain cortical volume, particularly the medial temporal lobe, but not by aging or ischemic stroke.ConclusionOverall, the study provides evidence supporting a causal relationship between hearing impairment and increased risks of different types of dementia (including AD, FTD, and DLB), as well as poorer general cognitive function. These findings underscore the importance of addressing hearing impairment as a modifiable risk factor for dementia.

Key neuroprotective mechanisms of the MIND diet - a review paper

Introduction and purpose: Impaired cognitive function is a growing public health problem, where dementia is affecting about 47 million people worldwide, and that number is expected to triple by 2050. The MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet is intended to overcome this problem. This article aims to raise awareness of the MIND diet, highlighting how dietary choices can promote cognitive health and delay disease progression. Brief description of the state of knowledge: The MIND diet focuses on foods that support cognitive health and may mitigate these degenerative processes. It emphasizes green leafy vegetables, berries, nuts, olive oil, whole grains, fish, and poultry while limiting red meat, dairy, sweets, and fried foods. These products contain several components with multidirectional neuroprotective effects. Material and method: This work was based on material found on Google Scholar. Articles were selected based on citation counts, publication dates, and relevance, ensuring a comprehensive review of recent findings on the MIND diet's impact on cognitive health. Summary: The MIND diet enhances brain health by incorporating nutrient-dense foods that reduce inflammation, combat oxidative stress, and support neuronal function. Green leafy vegetables, berries, nuts, whole grains, and healthy fats work together to improve cognitive function, support synaptic plasticity, and protect brain structure, leading to slower cognitive decline and a lower risk of neurodegenerative diseases.

Tooth loss in young mice is associated with cognitive decline and femur-bone mineral density.

Osteoporosis is a prevalent disease that is associated with increased hip fractures which cause significant decline in quality of life. Tooth loss affects systemic condition such as cognitive function through various mechanism, but the link between tooth loss and femoral bone mineral density is still uncertain. This study aims to investigate whether tooth loss in young mice affects memory function and femoral bone mineral density. Eight-week-old male C57BL/6J mice were allocated randomly into the control group with sham operation and the tooth-loss group extracted all maxillary molar. Step-through passive avoidance test as cognitive function test, micro-CT analysis and western blotting analysis were performed after 1- and 2-month observation period. Step-through passive avoidance test revealed that the tooth-loss group in 2-month observation period impaired cognitive function. Additionally, micro-CT analysis revealed a significant decrease in both the length of the mandible and bone mineral density in the femur of the tooth-loss group compared to the control group. Claudin-5 level in the hippocampus, which is one of the tight junction markers in blood-brain-barrier, was significantly decreased in the tooth-loss group. The findings of our present study suggested that tooth loss impair cognitive function accompanied by reduced tight-junction marker, mandibular growth and bone mineral density of femur.

Pelayanan Fisioterapi Melalui Pemeriksaan Mini-Mental State Examination Untuk Menilai Fungsi Kognitif Lansia di RW 8 Kelurahan Tanjung Rejo Kota Malang

Impaired cognitive function is still a serious health problem that can cause psychological and socio-economic impacts in the form of social isolation and financial difficulties, delayed mobility, and worsening of other symptoms as well as reducing quality of life. As a basis for elderly health services, it is hoped that healthy elderly people will remain healthy. by optimizing physical, mental, cognitive and spiritual functions, through promotive and preventive efforts, including elderly empowerment activities. This counseling aims to assess cognitive function using the Mini Mental State Examination (MMSE) in the elderly at Posyandu for the elderly RW 8 Tanjung Rejo, Malang City. The method given is an examination using the Mini Mental State Examination (MMSE) questionnaire. The counseling process went smoothly. The results of the examination showed that the majority of elderly people had normal cognitive conditions. A good lifestyle can reduce the risk of dementia.

Projection of visual material on postoperative delirium in patients undergoing cardiac surgery: A double blind randomized clinical trial.

Postoperative delirium is a neurobehavioral disorder that can appear after surgery. It is characterized by an altered level of consciousness and impaired cognitive function. The aim of this study was to evaluate the impact of visual projection of images of relatives or loved ones in patients undergoing cardiac surgery in the immediate postoperative period, and its influence on the incidence and development of postoperative delirium. A randomized, double-blind clinical trial was designed in the immediate postoperative period of adult patients undergoing cardiac surgery. Consolidated Statement of Reporting Trials guidelines were followed. A control group (CG) and an intervention group (IG) were established. In the IG, the patients underwent a visual projection, while the usual unit treatment was carried out with the CG. Sociodemographic, anthropometric, anesthetic, and surgical variables were also recorded. The postoperative delirium assessment scale used was the confusion assessment method for diagnosing delirium in intensive care unit patients. Information was collected from 104 patients undergoing cardiac surgery. Most of the patients included in the study were men (66.35%) and the most performed surgical intervention was aortic valve replacement (34.62%). In the CG, positive patients in postoperative delirium increased from 19.23% to 25%, while in the IG they decreased from 5.77% to 1.92%. The logistic regression analysis presents a prediction model where the variables that influence the model are gender and group membership, meaning that being female and belonging to the IG significantly reduce the presence of delirium. The projection of visual material reduced the incidence of postoperative delirium in patients undergoing cardiac surgery, although it cannot be established that it is effective as a treatment once the pathology is already established.

HINT1 promotes neuronal apoptosis and triggers schizophrenia-like behavior in rats

This study aims to investigate the mechanism by which Histidine triad nucleotide-binding protein 1 (HINT1) promotes hippocampal neuronal apoptosis, triggering schizophrenia (SZ)-like behavior in rats. By establishing a rat SZ-like model, we assessed learning, memory, emotional response, and cognitive function through the Morris Water Maze, auditory startle response, and open field tests. HINT1 expression in the hippocampus was analyzed via RT-PCR and Western blot. We also created a HINT1 overexpression model in hippocampal neuronal cells to analyze its effects on cell proliferation and apoptosis. This analysis was conducted using the CCK-8 assay and flow cytometry, along with the quantification of apoptosis-related proteins and neurotrophic factors. Our findings indicated that the SZ-like model rats exhibited diminished learning and memory abilities, altered emotional reactions, and impaired cognitive functions, alongside a notable increase in HINT1 mRNA and protein levels. HINT1 overexpression was observed to inhibit hippocampal neuronal cell proliferation and promote apoptosis, with an increase in the expression of pro-apoptotic proteins and a decrease in neurotrophic factors. These results suggest HINT1's role in the onset and development of SZ-like behavior through its upregulation and induction of apoptosis in hippocampal neuronal cells, underlining its potential as a therapeutic target.

Predicted Expenditure for Prescription Drugs for Multiple Sclerosis in the Italian Market Between 2023 and 2028: Results of the Oracle Project.

Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028. A horizon-scanning model was developed to estimate annual expenditure from 2023 to 2028. Annual expenditure for MS was calculated by combining the number of patients treated with each product (clinical inputs) and the yearly costs of therapy (economic inputs). Baseline inputs (2020-2022) were collected from IQVIA® real-world data, while input estimation for the 5-year forecast was integrated with analog analyses and the insights of clinicians and former payers. The number of equivalent patients treated in 2028 in Italy was estimated at around 67,000, with an increase of 10% versus 2022. In terms of treatment pattern evolution, first-line treatments are expected to reduce their shares from 47% in 2022 to 27% in 2028, and Bruton tyrosine kinase inhibitors are expected to reach 23% of patient shares. Overall, expenditure for MS is estimated to decrease from €721 million in 2022 to €551 million in 2028, mainly due to losses of exclusivity and renegotiation of drug prices. Despite the increase in the number of patients treated for MS and the launch of new molecules that will reach high market penetration, the model confirmed sustainability for the Italian National Healthcare Service.

"Monitoring inflammatory, immune system mediators, and mitochondrial changes related to brain metabolism during space flight".

The possibility of impaired cognitive function during deep space flight missions or while living on a Martian colony is a critical point of concern and pleads for further research. In addition, a fundamental gap exists both in our understanding and application of countermeasures for the consequences of long duration space travel and/or living in an extreme environment such as on the Moon or Mars. Previous studies, while heavily analyzing pre- and post-flight conditions, mostly fail to appreciate the cognitive stressors associated with space radiation, microgravity, confinement, hostile or closed environments, and the long distances from earth. A specific understanding of factors that affect cognition as well as structural and/or physiological changes in the brains of those on a space mission in addition to new countermeasures should result in improved health of our astronauts and reduce risks. At the core of cognitive changes are mechanisms we typically associate with aging, such as inflammatory responses, changes in brain metabolism, depression, and memory impairments. In fact, space flight appears to accelerate aging. In this review, we will discuss the importance of monitoring inflammatory and immune system mediators such as nuclear factor kappa B (NF-κB), and mitochondrial changes related to brain metabolism. We conclude with our recommended countermeasures that include pharmacological, metabolic, and nutritional considerations for the risks on cognition during space missions.

Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances

BackgroundNeurodegenerative diseases (NDDs) are a diverse group of neurological disorders with progressive neuronal loss at specific brain regions, leading to impaired cognitive functioning, loss of neuroplasticity, severe neurological impairment, and dementia. The incidence of neurodegenerative diseases is increasing at an alarming rate with current treatments struggling to barely prolong the inevitable. The desperation to discover a therapeutic agent to treat neurodegenerative diseases and to aid in the process of healthy recovery has opened a gateway into natural pigments. HypothesisThe xanthophyll pigment lutein may bear the potential as a therapeutic agent against NDDs. ResultsLutein plays an important role in brain development, cognitive functioning, and improving neuroplasticity. In vitro and in vivo studies revealed the neuroprotective properties of lutein against NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia. The neuroprotective effect of lutein is evidenced by the reduction of free radicals and the simultaneous strengthening of the endogenous antioxidant systems by activating the NRF-2/ERK/AKT pathway. Further, it effectively suppressed mitochondrial aberrations, excitotoxicity, overaccumulation of metals, and its resultant complications. The immunomodulatory activity of lutein prevents neuroinflammation by hindering NF-κB nuclear translocation, regulation of NIK/IKK, PI3K/AKT, MAPK/ERK, JNK pathways, and ICAM-1 downregulation. Lutein also rescued the dysregulated cholinergic system and resolved memory defects. Along with its neuroprotective properties, lutein also improved neuroplasticity by enabling neurogenesis through increased GAP-43, NCAM, and BDNF levels. ConclusionLutein exhibits strong neuroprotective activities against various NDDs. Though the investigations are in the exploratory phase, this review presents the consolidation of scattered evidence of the neuroprotective properties of lutein and urges its further exploration in clinical studies.

Administration of Aripiprazole Alleviates Memory Impairment and Restores Damaged Glutamatergic System in 5xFAD Mice.

Many patients with Alzheimer's disease (AD) also have psychosis, and it has been reported that these patients have more severely impaired cognitive functions than patients without psychosis. The glutamatergic system in the brain is known to play an important role in memory and learning in the neural circuits. However, there has been limited research on how antipsychotic drugs affect the glutamatergic system of AD. Therefore, we aimed to investigate the effects of aripiprazole on the glutamatergic system in an animal model of AD using functional molecular imaging. In this study, 5xFAD mice were used as the animal model. At the age of 5months, the mice were divided into wild-type, vehicle control, and aripiprazole-treated groups (n = 6 per group). The aripiprazole-treated group was administered aripiprazole for 2months at a dose of 1mg·kg-1·day-1. At 7months of age, the animals underwent behavioral tests and glutamate positron emission tomography (PET) scans. The aripiprazole-treated group exhibited alleviated memory impairment in a novel object recognition test. Moreover, this group displayed 7-8% higher binding in the glutamate PET scan than the vehicle-treated 5xFAD group. Postmortem examination confirmed the recovery of glutamatergic damage. The administration of aripiprazole alleviated memory impairment and restored the damaged glutamatergic system in 5xFAD mice. Although the use of aripiprazole in AD patients may be a constraint in terms of safety, we confirmed the possibility that the administration of antipsychotic drugs can be effective in AD.