Improvement In Neurocognitive Function Research Articles

Neurocognitive function in procedures correcting severe aortic valve stenosis: patterns and determinants.

Neurocognitive changes occurring after a surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) procedure for the correction of severe aortic stenosis (AS) have not been widely addressed and, if addressed, have produced conflicting results. The purpose of this study is to identify the pre-procedural neurocognitive pattern and its determinants in a setting of elderly (>65 years) patients with severe AS undergoing SAVR or TAVI and the changes occurring at a 2-3 month follow-up. This was a prospective cohort study included in the Italian Registry on Outcomes in Aortic Stenosis Treatment in Elderly Patients. Patients were assessed both before and after (2-3 months) the procedure using the Montreal Cognitive Assessment (MoCA) test. Data on periprocedural demographics, clinical factors, and outcome measures were collected. Before the procedure, 70% of the patients demonstrated a MoCA score <23 points, which was indicative of cognitive dysfunction. The factors associated with neurocognitive dysfunction were age, functional capacity, chronic heart failure, and hemoglobin levels. After the procedure, there was an overall improvement in the MoCA score of the patients, but 28% of the patients showed a reliable worsening of their condition. The factors associated with MoCA worsening were platelet transfusions and the amount of red blood cell units transfused. The correction of severe AS leads to an improvement in neurocognitive function after 2-3 months. This improvement does not differentiate between SAVR and TAVI after matching for pre-procedural factors. The only modifiable factor associated with pre-procedural neurocognitive function is anemia, and anemia correction with red blood cell transfusions is associated with a worsening of neurocognitive function. This leads to the hypothesis that anemia correction before the procedure (with iron and/or erythropoietin) may limit the risk of a post-procedural worsening of neurocognitive function.

0812 Inconsistent improvements of neurocognitive function after adenotonsillectomy: a pediatric sleep-disordered breathing cohort study

Abstract Introduction Adenotonsillectomy (AT) is the most common surgical treatment for pediatric obstructive-sleep-apnea (OSA) with fair effectiveness. There are still controversies about the improvement of neurocognitive function after AT. This study investigates the changes of neurocognitive function after AT in preschool and school age children with OSA, including intelligence and attention, and explore the inconsistent improvements by comparing different evaluation tools. Methods 130 children with pediatric OSA were recruited, including 30 preschool and 100 school-age children. 125 participants underwent clinical evaluation, including polysomnography (PSG), before and 1-year after AT. Preschool children received the Wechsler-Preschool-and-Primary-Scale-of-Intelligence (the revised and IV edition, WPPSI-R and WPPSI-IV) and the Conners’-Kiddie-Continuous-Performance-Test (K-CPT) while school-age children received the Wechsler-Intelligence-Scale-for-Children (the 3rd and 4th edition, WISC-III and WISC-IV), and the Conners’-continuous-performance-test-II (CPT-II), before and 1-year after AT. Questionnaires including the Obstructive-Sleep-Apnea-Questionaire-18 (OSA-18) and Child-Behavior-Checklist (CBCL) were also used. The t-test and chi-square test analysis was used to compare data between preschool and school-age children, including PSG, CPT variables, intelligence variables, OSA-18 and CBCL before and after AT, as well as group differences in changes. Correlation analysis of CPT variables were performed by using the Pearson-Correlation to investigate factors related to treatment response. Results No significant group difference was found except age (p=0.000) and less male gender in preschool children (p=0.049). 21.7% of preschool children had language delay, and more than 80% of all children had allergic rhinitis or high narrow palate. After AT, both groups had significant improvement in PSG and OSA-18. No significant change was found by WPPSI-IV in the preschool children and WISC-IV in the school-age children, but significant improvements were found in preschool children and school-age children by WPPSI-R and WISC-III. There were also significant improvements of CPT-II in school-age children, and the Hit-reaction-time-standard-deviation positively correlates with the improvement in PSG. Conclusion Besides the improvement of sleep apnea and subjective improvements of emotion and behavior, AT can be beneficial in the neurocognitive function of preschool and school-age children with OSA, including intelligence and attention. Some tools may not be sensitive enough to detect the improvement in neurocognitive function, and selection of proper evaluation tools can be important in study design. Support (if any)

COMPREHENSIVE PROGRAM OF NEUROTHERAPY FOR A VISUAL ARTIST WITH POST- COVID-19 SYNDROME FOLLOWING SARS-COV-2 INFECTION AND SEVERE COURSE OF COVID-19 TREATED IN LONG-TERMPHARMACOLOGICALLY INDUCED COMA

The purpose of the study was twofold: (1) to present post-COVID-19 syndrome, which involves a variety of ongoing neurological, neuropsychiatric, neurocognitive, emotional and behavioral disorders resulting from SARS-CoV-2 infection followed by a severe course of COVID-19 treated in long term pharmacologically induced coma in a visual artist, which impacted on her artwork; (2) to present QEEG/ERP results and neuropsychological testing results in the evaluation of the effectiveness of a comprehensive neurotherapy program, with individualized EEG-Neurofeedback, and art-therapy in the reduction of post-COVID-19 syndrome in this artist.Ms. G., 42, a visual artist, portraitist, with good health, became ill in May 2022. Allegedly flu symptoms appeared first. After a few days, shortness of breath joined in. The PCR test for SARS-CoV-2 was positive. The patient was hospitalized, referred to the ICU, put on a respirator and treated over 11days of a pharmacologically induced coma. Two months after leaving hospital the patient developed post-COVID-19 syndrome. She was diagnosed by an interdisciplinary team: a neurologist, neuropsychiatrist and neuropsychologist. A PET scan of her brain revealed extensive changes involving a loss of metabolism in various brain areas. The presence of complex post-COVID, neurological, neuropsychiatric, neurocognitive, emotional and behavioral disorders was found and a neuropsychiatrist suggested a diagnosis of post-COVID schizophrenia. She was refered to the Reintegration and Training Center of the Polish Neuropsychological Society.We tested the working hypothesis as to the presence of schizophrenia and there was no reduction in the difference of ERPs waves under GO/NOGO task conditions. The absence of a neuromarker for schizophrenia allowed us to exclude this diagnosis and to propose a new disease entity, that being post-COVID-19 syndrome. She received a comprehensive two-component program of neurotherapy: (1) program A, consisting in goal-oriented neuropsychological rehabilitation, including art therapy, and (2) program B, based on the most commonly used form of EEG-Neurofeedback: frequency/ power EEG-Neurofeedback, using 2 bipolar surface electrodes, with the protocols written for her specific needs. The comprehensive neurotherapy program lasted 10 weeks, EEG Neurofeedback and art therapy classes were conducted 3 times a week for 45 minutes each. We found that after the completion of the comprehensive neurotherapy program there was a statistically significant reduction in high beta activity compared to the normative HBI database, which is associated with a reduction of anxiety. Also, we observed the improvement of neurocognitive functioning in neuropsychological testing (a significant reduction of anxiety and a noticeable improvement in neurocognitive functions). It should be stressed that the artist was happy that she had regained the ability to create, and even sells her artwork, although her style of painting had changed.Almost all the neurological, psychiatric, neurocognitive, emotional and behavioral disturbances, were reduced in their severity. The artist showed marked improvement and was able to return to painting. The artwork she produced after her illness is in high demand with art collectors. It can be also helpful in the reintegration of the Self System, and the improvement in her quality of life. Human Brain Index (HBI) methodology might be very useful in diagnosing and developing therapies for patients with Post-COVID-19 Syndrome.

Neurocognitive Functions after Stereotactic Radiosurgery - An Analysis with Mini-Mental State Examination (MMSE)

Background: Throughout the past decade, the research on neuro-oncology has increased awareness regarding the significance of cognitive functions as an outcome in different treatment modalities for patients with a primary brain tumor but only limited studies have explored the subject of the likelihood of cognitive dysfunction in patients undergoing stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT). This, modern radiation delivery technique allows high-dose delivery to the target and minimum dose to the brain/critical organs resulting in better tumor control and perhaps an improvement in Neurocognitive functions (NCF). Objectives: To explore the effect of stereotactic radiosurgery/stereotactic radiotherapy on neurocognitive functions (NCF) in various brain tumors. Methods: A prospective observational study was conducted at Neurospinal and Cancer Care Institute (NCCI), Karachi. A total of 100 patients who had undergone multisession stereotactic radiosurgery /stereotactic radiotherapy were selected after taking their written informed consent by employing a convenient sampling technique. The type of tumor was classified and identified on a radiological and histological basis. Neurocognitive function evaluation was carried out through Mini-Mental State Examination (MMSE) score questionnaire provided to patients at baseline (pre-radiosurgery SRS/SRT), and 6 months after treatment (post-radiosurgery SRS/SRT). Results: The mean age of patients was 37.38±15.03 years and the majority (49%) belonged to the 27-44 years age group. The majority of them were males whereas the most common pathology found was glioma (31%). Moreover, both overall and in patients having prior surgery, the comparison of different MMSE score levels showed that there was a significant increase in patients with normal score levels and a significant decrease in patients with mild and moderate score levels after treatment (P=0.006 and P=0.046 respectively) at post-treatment time. Conclusion: Stereotactic radiosurgery results in the improvement of neurocognitive functions. Previously known radiation-related impairment of NCF should be re-explored in light of modern radiosurgery/radiotherapy techniques with larger studies.

ILB®, a Low Molecular Weight Dextran Sulphate, Restores Glutamate Homeostasis, Amino Acid Metabolism and Neurocognitive Functions in a Rat Model of Severe Traumatic Brain Injury.

In a previous study, we found that administration of ILB®, a new low molecular weight dextran sulphate, significantly improved mitochondrial functions and energy metabolism, as well as decreased oxidative/nitrosative stress, of brain tissue of rats exposed to severe traumatic brain injury (sTBI), induced by the closed-head weight-drop model of diffused TBI. Using aliquots of deproteinized brain tissue of the same animals of this former study, we here determined the concentrations of 24 amino acids of control rats, untreated sTBI rats (sacrificed at 2 and 7 days post-injury) and sTBI rats receiving a subcutaneous ILB® administration (at the dose levels of 1, 5 and 15 mg/kg b.w.) 30 min post-impact (sacrificed at 2 and 7 days post-injury). Additionally, in a different set of experiments, new groups of control rats, untreated sTBI rats and ILB®-treated rats (administered 30 min after sTBI at the dose levels of 1 or 5 mg/kg b.w.) were studied for their neurocognitive functions (anxiety, locomotor capacities, short- and long-term memory) at 7 days after the induction of sTBI. Compared to untreated sTBI animals, ILB® significantly decreased whole brain glutamate (normalizing the glutamate/glutamine ratio), glycine, serine and γ-aminobutyric acid. Furthermore, ILB® administration restored arginine metabolism (preventing nitrosative stress), levels of amino acids involved in methylation reactions (methionine, L-cystathionine, S-adenosylhomocysteine), and N-acetylaspartate homeostasis. The macroscopic evidences of the beneficial effects on brain metabolism induced by ILB® were the relevant improvement in neurocognitive functions of the group of animals treated with ILB® 5 mg/kg b.w., compared to the marked cognitive decline measured in untreated sTBI animals. These results demonstrate that ILB® administration 30 min after sTBI prevents glutamate excitotoxicity and normalizes levels of amino acids involved in crucial brain metabolic functions. The ameliorations of amino acid metabolism, mitochondrial functions and energy metabolism in ILB®-treated rats exposed to sTBI produced significant improvement in neurocognitive functions, reinforcing the concept that ILB® is a new effective therapeutic tool for the treatment of sTBI, worth being tested in the clinical setting.

HIV Associated Neurocognitive Disorders Subsidence Through Citalopram Addition in Anti-retroviral Therapy (HANDS-CARE): A Concept Note.

There is a pressing need to effectively manage HIV Associated Neurocognitive Disorders (HAND) in sub-Saharan Africa (SSA) where the burden is among the highest in the world. Contemporary approaches based on the use of Highly Active Antiretroviral Therapy (HAART) alone are inadequate interventions for HAND, especially in SSA where there is limited availability of the required combinations of HAART for effective central nervous system penetration and where many currently prescribed agents, including efavirenz, have neurotoxicity as a major drawback. This article reviews data supporting the rationale for additive citalopram in antiretroviral therapy as a latent approach to abate HAND. It proposes the conduct of a HIV Associated Neurocognitive Disorders Subsidence through Citalopram addition in Anti-Retroviral therapy (HANDS-CARE) pilot feasibility trial (RCT) to assess whether the adjunctive use of citalopram, a widely prescribed serotonergic antidepressant, will lead to a meaningful improvement in neurocognitive functioning and quality of life in patients with HAND who are receiving HAART. A preliminarily feasible and efficacy-suggesting HANDS-CARE trial could generate statistical, clinical and operational data necessary to design and conduct a future definitive RCT. If successful, this intervention will be applicable to resource-limited settings as well as developed countries. Effective management of HAND will improve the quality of life of HIV patients, and reduce the cost of managing the disease.

A systematic review of endovascular treatment for chronic total occlusion of the internal carotid artery.

The management of patients with symptomatic chronic total occlusion (CTO) of the internal carotid artery (ICA) is controversial. The aim of this systematic review was to investigate patient selection, technical success, early and late outcome of endovascular treatment for CTO of the ICA. PubMed/Medline and EMBASE databases were searched until January 2, 2020 for studies on endovascular treatment for CTO of the ICA. A descriptive analysis of demographic, clinical and anatomic data, endovascular technique, perioperative and late outcomes was performed. A total of 1,222 articles were screened, 8 retrospective or prospective cohort studies were reviewed; 276 patients, 18.9% females, mean age: 64.3 years, underwent attempt at endovascular treatment of 278 lesions. Two hundred and thirteen patients (77.2%) had neurological symptoms; the others had evidence of ipsilateral cerebral hypoperfusion. Two hundred and thirty-eight lesions (91.2%) were treated >30 days after diagnosis of occlusion. Technical success was 66.9%. Perioperative mortality was 1.64% (4/243), early stroke rate was 3.3%. Follow-up averaged 23.4 months (range, 0.25–84 months), late mortality was 1.89% (5/265), stroke rate was 3.4% (9/265). Stroke rate was similar after successful stenting (3.57%, 4/112) vs. failed stenting (3.61%, 2/61; P=1.00), stroke/death rates were also similar after successful stenting (5.36%, 6/112) than after failed stenting (3.28%, 2/61; P=0.71). Endovascular treatment of CTO of the ICA in eight cohort studies was safe and feasible with a technical success of 67% and a low rate of early and late neurological complications. Pooled data in this review failed to confirm the benefit of successful stenting on stroke and mortality, but some of the included studies suggest benefit and some also supported improvement in neurocognitive function after successful stenting. Prospective randomized trials to investigate the benefit of endovascular treatment in addition to best medical therapy for symptomatic CTO of the ICA are urgently needed.

Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection.

The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI). Single-arm, open-label pilot study of participants with AHI initiating ritonavir-boosted darunavir 800 mg once daily and etravirine 400 mg once daily or 200 mg twice daily within 30 days of AHI diagnosis. Efficacy was defined as HIV RNA less than 200 copies/ml by week 24. Optional sub-studies included pharmacokinetics analysis from genital fluids (weeks 0-4, 12, 48), cerebrospinal fluid (CSF) (weeks 2-4, 24 and 48) and endoscopic biopsies (weeks 4-12 and 36-48). Neuropsychological performance was assessed at weeks 0, 24 and 48. Fifteen AHI participants were enrolled. Twelve (80%) participants achieved HIV RNA less than 200 copies/ml by week 24. Among 12 participants retained through week 48, nine (75%) remained suppressed to less than 50 copies/ml. The median time from ART initiation to suppression less than 200 and less than 50 copies/ml was 59 and 86 days, respectively. The penetration ratios for etravirine and darunavir in gut associated lymphoid tissue were 19.2 and 3.05, respectively. Most AHI participants achieving viral suppression experienced neurocognitive improvement. Of the three participants without overall improvement in neurocognitive functioning as measured by impairment ratings (more than two tests below 1 SD), two had virologic failure. NRTI-sparing ART started during AHI resulted in rapid viral suppression similar to NRTI-based regimens. More novel and compact two-drug treatments for AHI should be considered. Early institution of ART during AHI appears to improve overall neurocognitive function and may reduce the risk of subsequent neurocognitive impairment. CLINICALTRIALS.GOV:: NCT00855413.

Carotid Endarterectomy Is Associated With Postoperative Neurocognitive Improvement in Both Symptomatic and Asymptomatic Patients

While stroke after carotid endarterectomy (CEA) is rare, magnetic resonance imaging shows that “silent” microinfarctions after surgery are much more common. These microinfarcts have been correlated with neurocognitive decline. However, there is also evidence that revascularization may improve overall cognition due to improved cerebral blood flow and elimination of embolic source. As part of a trial of remote ischemic preconditioning as a possible neuroprotective mechanism during CEA, we examined the overall impact of carotid revascularization on cognitive function. This is an interim noncomparative analysis of the cohort enrolled in an institutional randomized trial for the role of remote ischemic preconditioning for CEA (RIP-CEA, NCT02808754). All patients underwent baseline neurocognitive testing using the Montreal-Cognitive Assessment (MoCA) and National Institutes of Health Toolbox (Flanker Inhibitory Control and Attention Test, the Dimensional Change Card Sort Test, and the Pattern Comparison Processing Speed Test). These tests specifically assess executive function and processing speed. MoCA was also conducted on postoperative day 1 in the hospital. The full neurocognitive testing battery was conducted again at the 1-month follow-up in the office. Score changes from baseline were examined at the follow-up time points. Eighty patients with a mean age of 71.3 ± 7.1 years (65% male, and 30% symptomatic) were enrolled. The average baseline MoCA score was 24.7 ± 2.8 and this was similar between symptomatic and asymptomatic patients (P = .6). Forty-seven percent of patients met criteria for cognitive decline (MoCA < 26) at baseline. While MoCA scores remained unchanged immediately postoperatively, patients experienced significant improvements in MoCA scores by 1 month after CEA (average MoCA score of 26.3 and only 26% qualifying as cognitive decline; P < .001). Similarly, patients experienced significant improvements in executive function (26.4 ± 4.7 months before CEA vs 28.3 ± 2.3 1 months after CEA; P < .001) and processing speed at 1 month after CEA (31.8 ± 9.2 months before CEA vs 35.8 ± 8.4 1 months after CEA; P < .001) as assessed by the National Institutes of Health toolbox. There was no difference in the number or degree of cognitive improvement between symptomatic and asymptomatic patients. Statin use was a significant predictor of improvement on MoCA score at 1 month (OR, 3.9; P < .05). Carotid revascularization with CEA is associated with significant improvements in neurocognitive function by one month post operatively across multiple domains. Statin use may be further protective. Longer term follow-up is needed to see the magnitude and durability of these cognitive improvements. Neurocognitive improvement following CEA may justify reconsideration of the role of carotid revascularization in asymptomatic patients.

Amantadine and Modafinil as Neurostimulants During Post-stroke Care: A Systematic Review.

Amantadine and modafinil are neurostimulants that may improve cognitive and functional recovery post-stroke, but the existing study results vary, and no comprehensive review has been published. This systematic review describes amantadine and modafinil administration practices post-stroke, evaluates timing and impact on clinical effectiveness measures, and identifies the incidence of potential adverse drug effects. A librarian-assisted search of the MEDLINE (PubMed) and EMBASE databases identified all English-language publications with "amantadine" or "modafinil" in the title or abstract from inception through February 1, 2020. Publications meeting predefined Patient, Intervention, Comparator, Outcome (PICO) criteria were included: Patients (≥ 18years of age post-stroke); Intervention (amantadine or modafinil administration); Comparison (pretreatment baseline or control group); Outcomes (cognitive or functional outcome). Amantadine and modafinil administration practices, cognitive and functional outcomes, and incidence of potential adverse drug effects were collected following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance. Quantitative analyses were not performed due to heterogeneity in the clinical effectiveness measures; descriptive data are presented as number (percent) or median (interquartile range). Of 12,620 publications initially identified, 10 amantadine publications (n = 121 patients) and 12 modafinil publications (n = 120 patients) were included. Amantadine was initiated 39 (16, 385) days post-stroke, with most common initial doses of 100mg once or twice daily (range 100-200mg/day), and final daily dose of 200 (188, 200) mg/day. Modafinil was initiated 170 (17, 496) days post-stroke, with initial and final daily doses of 100 (100, 350) mg/day and 200 (100, 350) mg/day, respectively. The most common indication was consciousness disorders for amantadine (n = 3/10 publications; 30%) and fatigue for modafinil (n = 5/12; 42%). Forty unique clinical effectiveness measures (1.8 per study) with 141 domains (6.4 per study) were described across all studies. A positive response in at least one clinical effectiveness measure was reported in 70% of amantadine publications and 83% of modafinil publications. Only one publication each for amantadine (10%; n = 5 patients) and modafinil (8%; n = 21 patients) studied acutely hospitalized or ICU patients; both were randomized studies showing improvements in neurocognitive function for amantadine and fatigue for modafinil. Potential adverse drug effects were reported in approximately 50% of publications, most commonly visual hallucinations with amantadine (2% of patients) and dizziness (5% of patients) and dry eyes or mouth (5% of patients). Amantadine and modafinil may improve cognitive and functional recovery post-stroke, but higher-quality data are needed to confirm this conclusion, especially in the acute care setting.

Second-generation long-acting injections anti-psychotics improve executive functions in patients with schizophrenia: a 12-month real-world study

Background: The main purpose of this study was to assess possible modifications of cognitive performance among schizophrenia patients treated with long-acting injectable antipsychotics (LAIs) of second generation anti-psychotics (SGAs). Our hypothesis is that the shift from the oral formulation to the LAI formulation of SGAs drugs improves the cognitive performance. The secondary objective was to carry out a head to head comparison of two different SGA-LAI treatments [i.e., 1-month Paliperidone Palmitate (PP1M), monthly Aripiprazole (Ari-LAI)] in our study with an independent and real-world setting.Methods: The sample comprised 32 participants who were consecutively recruited over 12 months. Seventeen patients treated with Ari-LAI and 10 treated with PP1M completed psychopathological, neuropsychological and functional assessments. Group differences were explored through chi-squared and t-tests, as appropriate. GLM Repeated Measures were used to study variations of cognitive performance along 12 months and to test differences between drugs.Results: We found an effect of time on the outcomes investigated but this did not depend on the type of LAI used.Conclusions: In comparison with the previous oral treatment with SGAs, patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI. Furthermore, there were no differences between the SGA-LAI regimens.Key pointsThe main purpose of this study was to assess possible modification of cognitive performance of patients with Schizophrenia treated with second generation long-acting injectable antipsychotics (SGA-LAIs).The secondary objective was to carry out a head to head comparison of two different SGA-LAIs: Paliperidone Palmitate 1-Month (PP1M) and Aripiprazole Monthly (Ari-LAI).Patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI.There were no differences between the SGA-LAI regimens.From a practical point of view, switching to LAI formulation seems to produce further social and cognitive improvements in patients who had already benefitted from oral SGA therapy.

Plasma levels of 3-methoxy-4-hydroxyphenylglycol levels, number of hospitalization and cognitive function predicts the cognitive effect of atypical antipsychotic monotherapy in patients with acute schizophrenia.

Although the effects of atypical antipsychotics with regard to improving neurocognitive function are not sufficiently high. The present study applied an atypical antipsychotic monotherapy for patients with acute schizophrenia to (1) examine the percentage of patients who respond well to this treatment, (2) explore the factors that predict response (e.g. the improvement of neurocognition), and (3) identify the factors associated with improved neurocognitive function. We studied 40 patients with acute schizophrenia who had received atypical antipsychotic monotherapy for 24 weeks. The following parameters were evaluated at baseline and 24 weeks after the start of treatment: psychotic symptoms, neurocognitive function, and blood biological markers including homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, and brain-derived neurotrophic factor. Marked improvements in neurocognitive function were noted in 7.5%-25% of patients. The factors that significantly predicted neurocognitive function improvement were the frequency of hospitalization (verbal memory and verbal fluency), 3-methoxy-4-hydroxyphenylglycol (verbal fluency and executive function), and verbal memory (working memory). Approximately 20% of the patients showed good response to treatment with antipsychotics. Frequency of hospitalization, 3-methoxy-4-hydroxyphenylglycol level, and other parameters predicted responsiveness to these drug therapies. Thus, it might be useful to apply these factors to predict responses to treatment.

Effects of abstinence of alcohol on neurocognitive functioning in patients with alcohol dependence syndrome.

Alcohol dependence causes impairment of neurocognitive functions. Abstinence for some time leads to improvement in neurocognitive functions. This study was conducted with the aim to observe the effects of abstinence on neurocognition. The current study was an observational, single group with longitudinal design exploring the effect of abstinence on neuropsychological functioning and further exploring correlation of clinical factors with neuropsychological functioning in patients with Alcohol Dependence Syndrome (ADS). Sixty consecutive male patients of ADS meeting inclusion and exclusion criteria were inducted. Neurocognitive tests were applied at baseline, one month and three months of abstinence. All neurocognitive functions showed significant improvement at three-time intervals (p < 0.05) except for visuomotor function, for which improvement was statistically insignificant (p > 0.05) at one month. The difference for scores on verbal fluency, working memory, set-shifting (WCST total trials and perseverative errors) and visuomotor function from 0 to 3 months was significant (p < 0.05). There was significant interaction (p < 0.05) between duration of regular but non-dependent use, total duration of use, duration of dependence, average intake per day, last intake and time period with verbal fluency, working memory, set -shifting (for WCST total trials, total errors, perseverative errors and non-perseverative errors) and visuomotor function. The study showed improvement in neurocognitive functions with abstinence over three months, suggesting the need to address these cognitive deficits in the early part of abstinence. Also, correlates for drinking history were identified which may help in the future for the prevention and management of cognitive deficits in ADS patients.

Impact of bariatric surgery on cerebral vascular reactivity and cognitive function: a non-randomized pilot study

BackgroundBariatric surgery is an effective long-term weight loss strategy yielding improvements in neurocognitive function; however, the mechanism(s) responsible for these improvements remains unclear. Here, we assessed the feasibility of using magnetic resonance imaging (MRI) to evaluate whether cerebral vascular reactivity (CVR) is impaired in severely obese bariatric surgery candidates compared with normal weight healthy controls and whether CVR improves following bariatric surgery. We also investigated whether changes in CVR were associated with changes in cognitive function.MethodsBariatric surgery candidates (n = 6) were compared with normal weight healthy controls of a similar age (n = 10) at baseline, and then reassessed 2 weeks and 14 weeks following sleeve gastrectomy bariatric surgery. Young reference controls (n = 7) were also studied at baseline to establish the range of normal for each outcome measure. Microvascular and macrovascular CVR to hypercapnia (5% CO2) were assessed using blood-oxygen-level-dependent (BOLD) MRI, and changes in the middle cerebral artery (MCA) cross-sectional area, respectively. Cognitive function was assessed using a validated neurocognitive software.ResultsCompliance with the CVR protocol was high. Both macro- and micro-cerebrovascular function were highest in the young reference controls. Cognitive function was lower in obese bariatric surgery candidates compared with normal weight controls, and improved by 17% at 2 weeks and 21% by 14 weeks following bariatric surgery. To our surprise, whole-brain CVR BOLD did not differ between obese bariatric surgery candidates and normal weight controls of similar age (0.184 ± 0.101 vs. 0.192 ± 0.034 %BOLD/mmHgCO2), and did not change after bariatric surgery. In contrast, we observed vasoconstriction of the MCA during hypercapnia in 60% of the obese patients prior to surgery, which appeared to be abolished following bariatric surgery. Improvements in cognitive function were not associated with improvements in either CVR BOLD or MCA vasodilation after bariatric surgery.ConclusionsAssessing CVR responses to a hypercapnic challenge with MRI was feasible in severely obese bariatric patients. However, no changes in whole-brain BOLD CVR were observed following bariatric surgery despite improvements in cognitive function. We recommend that future large trials assess CVR responses to cognitive tasks (rather than hypercapnia) to better define the mechanisms responsible for cognitive function improvements following bariatric surgery.

Randomized trial to assess safety/feasibility of memantine administration during residential treatment for alcohol use disorder: a pilot study

The N-methyl-D-aspartate receptor (NMDAr) system is critically involved in the pathogenesis and neurobehavioral sequelae of alcohol use disorder (AUD), and constitutes a potential pharmacotherapeutic target. Memantine (Namenda) is an FDA-approved NMDAr antagonist with suggested utility in AUD, however its safety and tolerability during long-term administration among recently-detoxified patients remains uncharacterized. This pilot study assessed safety, feasibility, and several secondary measures of interest, during a 4-week period of residential AUD treatment. Participants (N = 18) met diagnostic criteria for AUD. A double-blind, placebo-controlled, escalating-dose design was utilized. Assessments of medication side-effects were conducted weekly. At intake, week 2, and study completion, participants completed a battery assessing affective symptomatology, craving, and neurocognitive function. Medication groups reported equivalent side effects and severity. Medication compliance was high, and did not differ by group. No memantine effects were observed in secondary outcome measures. Memantine maintains a profile of high tolerability and low side-effects during post-detoxification AUD treatment. These data suggest a more aggressive dosing/escalation schedule may be used safely in future trials designed to ascertain improvements in neurocognitive function, affect, and/or craving as primary measures.

Housing Stability and Neurocognitive Functioning in Homeless Adults With Mental Illness: A Subgroup Analysis of the At Home/Chez Soi Study.

Objective: This study examined the association of housing stability with neurocognitive outcomes of a well-characterized sample of homeless adults with mental illness over 18 months and sought to identify demographic and clinical variables associated with changes in neurocognitive functioning.Method: A total of 902 participants in the At Home/Chez Soi study completed neuropsychological measures 6 and 24 months after study enrollment to assess neurocognitive functioning, specifically verbal learning and memory, cognitive flexibility, and complex processing speed. Multivariable linear regression was performed to assess the association of housing stability with changes in neurocognitive functioning between 6 and 24 months and to examine the effect of demographic and clinical variables on changes in neurocognitive functioning.Results: Overall neurocognitive impairment remained high over the study period (70% at 6 months and 67% at 24 months) with a small but significant improvement in the proportion of those experiencing more severe impairment (54% vs. 49% p < 0.002). Housing stability was not associated with any of the neuropsychological measures or domains examined; improvement in neurocognitive functioning was associated with younger age, and bipolar affective disorder at baseline.Conclusions: The high prevalence and persistence of overall neurocognitive impairment in our sample suggests targeted approaches to improve neurocognitive functioning merit consideration as part of health interventions to improve everyday functioning and outcomes for this population. Further efforts are needed to identify potential modifiable factors that contribute to improvement in cognitive functioning in homeless adults with mental illness.

Effect of Environment Enrichment (SPARK Perceptual-Motor Exercises) on the Improvement of Neurocognitive Functions in Children with Developmental Coordination Disorder

Effect of Environment Enrichment (SPARK Perceptual-Motor Exercises) on the Improvement of Neurocognitive Functions in Children with Developmental Coordination Disorder

Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 15-year follow-up study.

To evaluate the course of neuropsychological impairment, patients with first-episode schizophrenia and healthy controls were assessed with a comprehensive test battery at the time of index treatment and after a 5- and 15-year follow-up period. Summary scores for verbal intelligence (VBI), spatial organization, verbal fluency, verbal learning, semantic memory, visual memory, delay/retention rate, short-term memory, visual-motor processing and attention (VSM) and abstraction/flexibility were constructed. Our results show that neurocognitive functioning is impaired already at the onset of schizophrenia and remains stable over the 15-year follow-up period with an improvement in VBI. With regard to the presence of a deficit syndrome, it became apparent that the group with a deficit syndrome showed a deterioration of neurocognitive functions during the follow-up period, most pronounced in VSM. On the other hand, the group without a deficit syndrome showed an improvement in neurocognitive functions at the 15-year follow-up, which exceeded the learning effects of healthy control subjects. Neurocognitive performance at index assessment strongly predicted the performance at the 15-year follow-up. Most likely due to the small sample size, there were only weak associations between treatment with different types of neuroleptics and neurocognitive performance.

Cognitive and cerebral hemodynamic effects of endovascular recanalization of chronically occluded cervical internal carotid artery: single-center study and review of the literature.

Revascularization of a symptomatic, medically refractory, cervical chronically occluded internal carotid artery (COICA) using endovascular techniques (ETs) has surfaced as a viable alternative to extracranial-intracranial bypass. The authors aimed to assess the safety, success, and neurocognitive outcomes of recanalization of COICA using ETs or hybrid treatment (ET plus carotid endarterectomy) and to identify candidate radiological markers that could predict success. The authors performed a retrospective analysis of their prospectively collected institutional database and used their previously published COICA classification to assess the potential benefits of ETs or hybrid surgery to revascularize symptomatic patients with COICA. Subjects who had undergone CT perfusion (CTP) imaging and Montreal Cognitive Assessment (MoCA) testing, both pre- and postprocedure, were included. The authors then performed a review of the literature on patients with COICA to further evaluate the success and safety of these treatment alternatives. The single-center study revealed 28 subjects who had undergone revascularization of symptomatic COICA. Five subjects had CTP imaging and MoCA testing pre- and postrevascularization and thus were included in the study. All 5 patients had very large penumbra involving the entire hemisphere supplied by the ipsilateral COICA, which resolved postoperatively. Significant improvement in neurocognitive outcome was demonstrated by MoCA testing after treatment (preprocedure: 19.8 ± 2.4, postprocedure: 27 ± 1.6; p = 0.0038). Moreover, successful revascularization of COICA led to full restoration of cerebral hemodynamics in all cases. Review of the literature identified a total of 333 patients with COICA. Of these, 232 (70%) showed successful recanalization after ETs or hybrid surgery, with low major and minor complication rates (3.9% and 2.7%, respectively). ETs and hybrid surgery are safe and effective alternatives to revascularize patients with symptomatic COICA. CTP imaging could be used as a radiological marker to assess cerebral hemodynamics and predict the success of revascularization. Improvement in CTP parameters is associated with significant improvement in neurocognitive functions.

Effect of Methylphenidate and Duloxetine on Neurotoxicity in CAR-T: A Case Study

Introduction Chimeric Antigen Receptor (CAR) T-cell therapy is a promising therapy for B-cell malignancies; however, it is associated with serious adverse effects including cytokine release syndrome and neurotoxicity. The incidence of neurotoxicity in two landmark trials ranged from 40-64%.1,2 Common signs and symptoms of neurotoxicity may include confusion, delirium, tremor, agitation, headache, personality changes, somnolence and dysphasia/aphasia. We report a case of severe neurotoxicity followed by significant depression and abulia. Methods We reviewed the case of a patient who experienced neurotoxicity after CD19 directed CAR T-cell therapy. The patient developed grade 2 neurotoxicity by CTCAE v4.0 consisting of aphasia, facial droop, nystagmus, tongue fasciculations, handwriting changes, and paranoid delirium. The patient was treated with intravenous dexamethasone 10mg every 6 hours with worsening of neurotoxicity during steroid taper. The patient was discharged on oral dexamethasone when medically stable then subsequently readmitted with different neurocognitive manifestations including failure to thrive, profound personality changes, passive suicidal ideation, abulia, paranoia, depression, and weakness. The patient had stopped taking all medications, including steroids, and refused all medical care. Steroids were not restarted due to steroid myopathy and psychosis. Infectious and structural complications were ruled out. Physical Medicine and Rehabilitation (PMR) was consulted. Based on evidence-based neuro-rehabilitation interventions, methylphenidate and duloxetine were recommended. Results The patient was started on methylphenidate 10mg twice daily and duloxetine extended release 30mg daily. Within 24 hours, the patient showed marked improvement with motivation to participate in medical care, improvement in anhedonia, and resolution of passive suicidal ideation. The patient showed significant improvement in physical function after participation in a multimodal inpatient rehabilitation program. Conclusion Significant improvement in neurocognitive function was seen within 24 hours after the initiation of methylphenidate and duloxetine. We propose this drug combination as a potential treatment in CAR-T patients with neurocognitive dysfunction as sequelae of neurotoxicity.