Reduction Of Cognitive Deficits Research Articles

Cognition in Schizophrenia: Exploring the Dynamics of Improvement and the Influencing Determinants

Background: Cognitive impairments are fundamental characteristics of schizophrenia, significantly impacting the overall functioning of individuals with the disorder. However, the trajectory of cognitive deficits and the factors influencing their changes over the course of treatment remain poorly understood. Objectives: The present study aimed to investigate the changes in cognitive status of patients with schizophrenia and the factors that influence these changes following hospitalization and treatment. Methods: The study utilized a longitudinal design, enrolling thirty hospitalized patients (15 males and 15 females) from the psychiatric inpatient unit of a general educational hospital. Cognitive assessments were conducted upon admission and discharge. A Generalized Estimating Equation (GEE) model was used to analyze the data, accounting for demographic and clinical variables such as age, gender, Body Mass Index (BMI), family history, and smoking status. Results: The findings revealed a reduction in cognitive deficits following hospitalization and treatment. Significant improvements were observed in verbal memory, working memory, and executive function. However, older patients showed poorer performance in motor speed, verbal fluency, and symbol coding compared to younger patients. Male patients and smokers demonstrated lower cognitive functioning, particularly in verbal fluency, symbol coding, and executive function. Conclusions: This study highlighted the positive effect of comprehensive inpatient treatment on reducing cognitive impairments in individuals with schizophrenia. While improvements were noted in several cognitive domains, the persistence of certain deficits, particularly in relation to demographic factors (age, gender, and smoking status), underscores the need for further research and tailored cognitive rehabilitation interventions. A personalized, multidimensional approach to managing cognitive deficits in schizophrenia could lead to better functional outcomes and enhance the quality of life for affected individuals.

Evaluation of biomarker, behavioral, and immunostimulatory profiles following treatment with Class C CpG ODN in a non‐human primate model of sporadic CAA

AbstractBackgroundInnate immunomodulation has shown potential to be an effective therapeutic approach in ameliorating pathological features of Alzheimer’s Disease (AD). Our recently published study showed a reduction in cognitive deficits and AD‐related pathology in a squirrel monkey model (SQM) of sporadic cerebral amyloid angiopathy (CAA) following treatment with TLR9 agonist, Class B CpG ODN. Subsequently, we commenced a chronic treatment study evaluating the efficacy and safety of Class C CpG ODN in geriatric SQMs. Here, we further explore the efficacy of Class C CpG ODN by evaluating fluid biomarkers and implementing automated cognitive tests. Moreover, we assess the immunostimulatory profiles induced by Class B and Class C CpG ODNs using RNA‐Seq genome‐wide transcriptome analysis of SQM PBMCs.MethodGeriatric SQMs received monthly injections of CpG ODN‐C or saline (VEH) over three years. Fluid biomarkers for cerebrovascular dysfunction, neurodegeneration, and neuroinflammation were assessed by Luminex and SIMOA. Touchscreen‐based Automated Cognitive Testing System (ACTS) was applied among socially living SQMs to assess behavioral changes. RNA‐Seq analyses were performed using PBMCs isolated 24hrs following CpG ODN‐B and ‐C administrations in a separate cohort of elderly SQMs.ResultOur initial experiments confirmed the utility of SQMs for investigating plasma age‐associated neurodegeneration biomarkers, including NfL, GFAP, and neurogranin. Preliminary evaluation of cerebrovascular dysfunction‐related plasma biomarkers, such as MMPs, albumin index, bFGF, and VCAM, revealed no differences between our treatment groups at earlier time points. Although not significant, higher levels of plasma sTREM2 and YKL‐40 were observed in VEH monkeys compared to CpG ODN‐treated group. Concluding assessments will be performed in plasma collected at the end of the treatment period. Characterization of additional plasma/CSF biomarkers related to AD/neurodegeneration is underway. ACTS‐based two‐choice discrimination learning task revealed that CpG ODN‐treated group performed with a greater correct response rate than the VEH group. As expected, RNA‐Seq analyses of SQM PBMCs revealed significantly altered pathways, including Th1/Th2, TLR signaling, phagocytosis, chemokine signaling, interferon signaling, and senescence pathways, in addition to pathways involved in infiltration, activation, and recruitment of various immune cells.ConclusionThe study highlights the potential of the SQM model for future translational research on CAA/AD and for advancing innovative therapeutic interventions.

Long-term outcomes of an internet-delivered cognitive enhancement intervention targeting residual cognitive deficits after major depressive disorder: a 2-year follow-up of an open trial.

Cognitive deficits are common and disabling residual symptoms following major depressive disorder (MDD) and are related to increased risk of relapse. Residual cognitive deficits should thus be considered an important target for treatment. However, few have reported long-term outcomes of interventions targeting residual cognitive deficits. This study aimed to (1) investigate change between pre-treatment and 2-year follow-up assessments in cognitive deficits, rumination, and symptoms of MDD after an internet-delivered intervention targeting residual cognitive deficits; (2) to investigate stability in outcomes between 6-month and 2-year follow-up assessments; (3) to report the number of participants' experiencing a new episode of MDD in the follow-up period; and (4) to investigate differences in outcomes between those who experienced a new episode of MDD and those who did not. A total of 43 partly remitted adults were included to test a guided internet-delivered intervention, which consisted of 10 modules involving psychoeducation, cognitive strategies, and attention training. Participants were assessed at pre-treatment, post-treatment, after 6-months, and after 2-years, with measures assessing self-reported residual cognitive deficits, rumination, symptoms of MDD and relapse. Overall, 32 participants completed the 2-year follow-up assessment. Between the pre-treatment and 2-year follow-up assessments, there was a reduction in cognitive deficits and rumination, while there was an increase in symptoms of MDD. Cognitive deficits were stable between the 6-month and the 2-year follow-up, while there was an increase in rumination and symptoms of MDD. Thirteen of 32 participants reported a new episode of MDD during the follow-up period. The relapse group reported longer duration of MDD at pre-treatment and showed a difference in all outcomes after 2 years compared to the no-relapse group. The no-relapse group showed improvement in MDD symptoms at post-treatment, while the relapse group did not. Delivering cognitive enhancement interventions over the internet is potentially related to stable improvements in residual cognitive deficits. The effects on rumination and symptoms of MDD are less certain. Lack of improvement in MDD symptoms after the intervention period should be investigated as an indicator of relapse. Results should be interpreted with caution due to the lack of control group and sample size.

Moderate coffee or tea consumption decreased the risk of cognitive disorders: an updated dose-response meta-analysis.

Although several epidemiological studies have examined the association between coffee or tea intake and the risk of cognitive disorders, the results to date are inconsistent. An updated systematic review and dose-response meta-analysis was conducted to confirm the association between coffee, tea, and caffeine consumption and the risk of cognitive disorders. PubMed, Embase, and Web of Science were searched from inception to January 2022 for relevant studies, including dementia, Alzheimer disease (AD), and cognitive impairment or decline. Two reviewers independently performed data extraction and assessed the study quality. Restricted cubic splines were used to conduct the dose-response meta-analysis for coffee and tea intake. Twenty-two prospective studies and 11 case-control studies involving 389 505 participants were eligible for this meta-analysis. Coffee and tea consumption was linked to a lower risk of cognitive disorders, with an overall relative risk (RR) of 0.73 (95% CI: 0.60-0.86) and 0.68 (95% CI: 0.56-0.80), respectively. The subgroup analysis revealed that ethnicity, sex, and outcomes had significant effects on this association. Protection was stronger for men than that for women in both coffee and tea consumption. A nonlinear relationship was found between coffee consumption and AD risk, and the strength of protection peaked at approximately 2.5 cups/day (RR: 0.74; 95% CI: 0.59-0.93). A linear relationship was found between tea consumption and cognitive disorders, and the risk decreased by 11% for every 1-cup/day increment. This meta-analysis demonstrated that the consumption of 2.5 cups coffee/day minimizes the risk of AD, and 1 cup/day of tea intake leads to an 11% reduction in cognitive deficits. Effective interventions involving coffee and tea intake might prevent the occurrence of dementia.

Dual-Tasking as Diagnostic and Rehabilitation Tool in Traumatic Brain Injury Patients

Objective: Purpose of this study was to investigate the behavioral and brain activity impairments in patients after moderate traumatic brain injury (mTBI) in comparison with the normal ranges while dual-tasks performing. We would like to evaluate dual-tasking as diagnostic and rehabilitation tool and to test hypothesis of brain aging after mTBI. Material and Methods: Electroencephalographic (EEG), stabilographic and clinical study was performed in 11 patients (mean age 28.8 ± 8.4 years) for up to 1 - 12 months after a mTBI in comparison with 17 healthy subjects (26.7 ± 5.1 years). All the participants performed two motor and two cognitive tasks presented separately, and simultaneously (dual-tasking). Results: Clinical examination revealed predominantly cognitive deficit in mTBI patients with intact postural control. EEG data demonstrated coherence decrease for slow (delta-theta) rhythms in frontal-temporal areas predominantly for left hemisphere during cognitive tasks performance. In contrast, EEG coherence for slow spectral bands increased in the same areas in healthy volunteers. EEG coherence increased for fast spectral bands—alpha2 and beta, predominantly in right hemisphere while both healthy adults and patients performed motor components of dual tasks. Rehabilitation course with dual tasks, led to a predominant reduction in cognitive deficits, and EEG coherence increases at the frontal-temporal areas of the left hemisphere. Conclusions: Dual-tasks may be used as diagnostic tool in patients after mTBI. This approach demonstrates predominant cognitive deficit, and left hemispheric dysfunction in patients similar to elderly persons and support the hypothesis of brain aging after TBI. Pilot studies also suggested rehabilitation effect of dual-tasking in mTBI patients.

Effectiveness of Cognitive Rehabilitation in Reduction of Cognitive Deficits of Amphetamine Dependents

The aim of present study was to investigate the effectiveness of Computer-assisted cognitive rehabilitation on reduction of cognitive deficits in working memory, sustained attention and reaction time in Amphetamine dependence patients. The design study was one participant experimental with multiple line bases. This figure is based on the different (3, 5 and 7) weeks and after finished baseline are included to treatment randomly. Participants divided into 3 groups and included in 3 mentioned baseline. First group has 3 baselines, second group has 5 and third group has 7 baseline and effectiveness of treatment for each group and compare to other groups is calculated and compared. Instruments were Wechsler Memory Scale (WMS), The Knox Cube Imitation Test and Continuous Performance Test. Our results showed that use of computers has led to reduced cognitive deficits (improved reaction time and working memory) in the patient that dependent on amphetamines.

IKKβ deficiency in myeloid cells ameliorates Alzheimer's disease-related symptoms and pathology.

Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Aβ clearance. However, studies examining innate immunity in Aβ pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKKβ, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKKβ in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and Aβ load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKKβ deficiency enhanced microglial recruitment to Aβ deposits and facilitated Aβ internalization, perhaps by inhibiting TGF-β-SMAD2/3 signaling, but did not affect Aβ production and efflux. Therefore, inhibition of IKKβ signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing Aβ clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression.

Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat

In previous studies, it has been shown that intravenous lactate therapy can improve brain neurochemistry, adenosine triphosphate (ATP) generation and outcome after traumatic brain injury (TBI) in rats. In this study, we examined: (1) four L-lactate concentrations to determine the optimal therapeutic dose post TBI in terms of cognitive function; (2) ATP production after TBI for the L-lactate concentration found to be the optimal dose; (3) the possible production of lactic acidosis with the highest L-lactate concentration tested. Thirty minutes following a fluid percussion injury (FPI) over the left cerebral hemisphere, the animals received an intravenous infusion of 10, 28, 100, or 280 mM L-lactate (n = 10 for each group) for 3 h at a rate of 0.65 ml/h. Shams and control injured animals received a saline infusion. At 11-15 days post injury, cognitive deficits were examined using the Morris Water Maze (MWM) test. Three groups of rats were used for ATP analysis: shams, injured + saline infusion, and injury + the optimal lactate dose as determined by the MWM (n = 4/group). Additionally, a group receiving 280 mM L-lactate (n = 5) and one receiving a saline infusion (n = 3) were monitored for arterial blood variables and blood pressures. In the MWM test, only the 100 mM L-lactate-treated injured animals showed a significant reduction in cognitive deficits when compared to saline-treated injured animals (p <or= 0.05). In the ATP study, injured animals without treatment had a 53% reduction in ATP level in the ipsilateral cortex, while animals with 100 mM lactate treatment had a 28% reduction. (p <or= 0.05). No lactic acidosis was induced by the intravenous infusion of 280 mM L-lactate. This study indicates that the intravenous infusion of 100 mM L-lactate provided the optimal concentration of the substrate to ameliorate cognitive impairment, probably via the regeneration of ATP following TBI in rats.

Generalized cognitive impairments, ability to perform everyday tasks, and level of independence in community living situations of older patients with psychosis.

This study examined the relationship between performance of instrumental activities of daily living, as measured with the University of California, San Diego, Performance-Based Skills Assessment (UPSA), and measures of cognitive functioning and independence in the community living situation of older outpatients with psychotic disorders. One hundred eleven middle-aged and elderly outpatients with primary psychotic disorders were administered the UPSA, the Mattis Dementia Rating Scale, and standardized measures of psychopathology. Independence in the community living situation was rated on a scale from 1 to 5, with 5 representing the highest level of independence, such as living alone in an apartment or house. Ability in seven domains of neuropsychological functioning was assessed in 67 participants. Total scores on the University of California, San Diego, Performance-Based Skills Assessment were significantly correlated with total and subscale scores on the Mattis Dementia Rating Scale, level of independence in the community living situation, and scores on the neuropsychological measures in the subset of patients who underwent neuropsychological testing. Lower scores on the Mattis Dementia Rating Scale memory subscale and more severe negative symptoms were significantly associated with worse performance on the skills assessment. Performance on the skills assessment contributed uniquely to prediction of independence in the community living situation. Generalized cognitive abilities are associated with everyday functioning capacity in older patients with psychosis. Reduction of cognitive deficits and negative symptoms may improve patients' ability to function independently in the community.

Fetal brain transplant: reduction of cognitive deficits in rats with frontal cortex lesions.

Frontal cortex and cerebellar tissue from fetal rats was implanted into the damaged frontal cortex of adults. Cognitive deficits in spatial alternation learning that follow bilateral destruction of medial frontal cortex were reduced in rats with frontal cortex implants but not in those with implants of cerebellum. Histological evaluation showed that connections were made between the frontal cortex implants and host brain tissue.