Neurocognitive Impairment In Patients Research Articles

Nadir oxygen delivery to the brain as a risk factor for post-operative neurocognitive impairment in patients undergoing coronary artery bypass grafting: A myth or fact

BackgroundThere are many factors that determine the best neurocognitive outcome following cardiac surgery. Optimum oxygen delivery to the tissues has always been the goal to optimum perfusion. Some patients may exhibit neurocognitive impairments in the early postoperative period; that could be easily missed clinically as they are not associated with radiographic evidence of structural brain damage. At this study we aimed to correlate the lowest oxygen delivery levels with incidence of neurocognitive impairment in the early postoperative period by Folstein test. MethodsA non-randomized, prospective pilot study was designed to correlate the nadir oxygen delivery (DO2) during CPB with post-operative cognitive impairment. The study included 271 patients of both sexes, an age group of 50–60 years with university level of education, scheduled for elective, isolated CABG for three vessel disease. All patients underwent pre-and post-operative neurocognitive test by a specialized neuropsychiatric doctor. Resultswith a mean nadir DO2 of 291 mL/min/m2, the majority of the patients exhibited “normal” results, with a mean nadir DO2 of 266 mL/min/m2 92 patients showed mild impairment in their cognitive behavior, while the worst results “moderate” and “severe” were associate with means of 244,200 mL/min/m2 successively. ConclusionsThe nadir oxygen delivery is a risk factor for development of post-operative neurocognitive impairment. A level below 260 mL/min/m2 is generally associated with higher risk while a level below 220 mL/min/m2 carries the worst prognosis.

Dysfunction of Nrf2-ARE Signaling Pathway: Potential Pathogenesis in the Development of Neurocognitive Impairment in Patients with Moderate to Severe Obstructive Sleep Apnea-Hypopnea Syndrome.

The present study investigated the nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response element (ARE) signaling pathway in patients with moderate to severe obstructive sleep apnea-hypopnea syndrome (OSAHS). Their correlation with neurocognitive impairment metrics was investigated to explore potential pathogenesis in OSAHS. Forty-eight patients with OSAHS and 28 controls underwent testing with the Epworth Sleep Scale (ESS), MATRICS Consensus Cognitive Battery (MCCB), Stroop Color and Word Test, polysomnography (PSG), and measurements of the concentration of plasma superoxide dismutase (SOD) and thioredoxin (Trx). Further, 20 pairs of matched patients with OSAHS and controls were selected for measurement of the expression (protein and mRNA) of Nrf2 and of its downstream antioxidase, heme oxygenase-1 (HO-1), in peripheral mononuclear cells (PBMCs). Finally, correlations between neurocognitive impairment and the above metrics were analyzed. Expression of Nrf2 and HO-1 mRNA and protein in the PBMCs, as well as plasma SOD and Trx levels, were significantly reduced in patients with OSAHS. After adjusting for education, sex, age, and smoking index, the expression of Nrf2-ARE signaling pathway proteins (or mRNA) was closely correlated with sleep respiratory parameters. An inverse relationship was demonstrated between the expression of nuclear Nrf2 in PBMCs, concentration of plasma SOD and Trx, and apnea-hypopnea index (AHI) in patients with OSAHS. Trx, nuclear Nrf2 protein, and HO-1 protein were also negatively correlated with the percent of time that SaO2 was less than 90% (TSat90). Total Nrf2 protein level was positively correlated with AHI and TSat90 and negatively correlated with minimum SaO2 (LSaO2), while nuclear Nrf2 protein and HO-1 protein were positively correlated with LSaO2. Moreover, significant positive correlations were found between maze scores and expression of nuclear Nrf2 protein, HO-1 protein, and SOD and Trx levels. Furthermore, inverse relationships between total Nrf2 protein in PBMCs and HVLT-R and maze scores were found. Multiple linear regression showed plasma Trx concentration as a potential predictor of maze and BVMT-R scores. In conclusion, the expression of Nrf2-ARE molecules and related antioxidases is significantly decreased in patients with OSAHS and is correlated with neurocognitive dysfunction. The Nrf2-ARE signaling pathway may play a crucial role in neurocognitive impairment in patients with moderate to severe OSAHS. Further studies are needed to explore the exact mechanisms and potential treatment interventions.

Neurocognitive impairment in patients with obstructive sleep apnea before and after therapy with continuous positive airway pressure

Neurocognitive impairment in patients with obstructive sleep apnea before and after therapy with continuous positive airway pressure

The perception and attention functions test battery as a measure of neurocognitive impairment in patients with suspected central disorders of hypersomnolence

The perception and attention functions test battery as a measure of neurocognitive impairment in patients with suspected central disorders of hypersomnolence

Training in a comprehensive everyday-like virtual reality environment compared to computerized cognitive training for patients with depression

Neurocognitive impairments in patients with depression compromise everyday functioning. Thus, should neuropsychological therapy be designed as real-life-like as possible to maximize transfer effects? We investigated whether ecological validity of computerized cognitive training could be increased by a comprehensive everyday-life-simulating training device combining virtual reality, 360°-all-around visibility and autonomous navigation motions. In an eight days training program, patients exercised the learning and purchasing of shopping list products in a virtual supermarket using either the novel training device (n = 21) or a corresponding desktop application (n = 17). In a pre-post-design, effects of the two training conditions were compared regarding several outcome measures. Altogether, results did not prove a benefit of the more naturalistic training setting regarding different training performances (recognition, performance speed, spatial orientation), self-perceived daily cognitive impairments, a real-life shopping task as well as various neuropsychological capabilities. Findings are discussed in the context of general challenges in striving after ecological validity in neuropsychology.

The Perception and Attention Functions test battery as a measure of neurocognitive impairment in patients with suspected central disorders of hypersomnolence.

The aim of the current study was to evaluate an attention test as a discriminative tool to measure neurocognitive impairment in patients with disorders of hypersomnolence. Chronic excessive daytime sleepiness is the main symptom in central disorders of hypersomnolence. For diagnostic purposes and treatment evaluation, reliable assessment of excessive daytime sleepiness is required. Thirty-six patients with central disorders of hypersomnolence were compared with 20 healthy controls. All participants performed the 'Perception and Attention Functions' (WAF) of the Vienna Test System. Patients underwent polysomnography, Multiple Sleep Latency Test and Maintenance of Wakefulness Test. Patients were divided into two groups: (i) patients who met the criteria of disorder of hypersomnolence (objective excessive daytime sleepiness); and (ii) patients with subjective excessive daytime sleepiness, i.e. with normal Multiple Sleep Latency Test results. Group 1 consisted of 23 patients with objective excessive daytime sleepiness (11 with idiopathic hypersomnia, nine with narcolepsy type 1, three with narcolepsy type 2); group 2 included 13 patients with subjective excessive daytime sleepiness. The results showed cognitive impairment in patients with objective excessive daytime sleepiness and even in patients with subjective excessive daytime sleepiness. WAF tests identified distinct attention profiles in patients with narcolepsy type 1, idiopathic hypersomnia/narcolepsy type 2, and patients with subjective excessive daytime sleepiness. WAF test measures correlated with Maintenance of Wakefulness Test and the Epworth Sleepiness Scale, but not with Multiple Sleep Latency Test and the Fatigue Severity Scale. In conclusion, the multidimensional WAF test battery detects cognitive impairment even in patients that complain of excessive daytime sleepiness but have normal Multiple Sleep Latency Test results. WAF tests offer valuable information that adds to the existing polysomnographic measures in discriminating patients with different types of chronic excessive daytime sleepiness. The results provide new insights into cognitive dysfunction underlying different types of chronic excessive daytime sleepiness.

Gene expression patterns associated with neurological disease in human HIV infection

The pathogenesis and nosology of HIV-associated neurological disease (HAND) remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI) in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE) and control subjects. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb). We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC), which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN), cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV infection and identify better therapeutic targets for NCI.

Neurocognitive status in different stages of psychosis: Changes from the first episode psychosis to remission

IntroductionNeurocognitive impairment in schizophrenia is associated with functional disability and poorer quality of life, and is the most resistant of all schizophrenia symptoms to current psychopharmacotherapy.ObjectivesTo compare the differences in neurocognitive status during the acute phase of first psychotic episode and stable symptomatic remission.AimsTo investigate the pattern of neurocognitive impairment in patients with first episode psychosis during acute phase and stable remission phase.MethodsWe performed a longitudinal study, including 150 patients with first episode of psychosis at two time points: during their hospitalization at Zagreb university hospital centre or university psychiatric hospital Vrapče, at acute phase of illness and after 12–18 months, during stable remission. Assessment included detailed clinical interview, clinical rating of neuropsychiatric symptoms using standardized psychiatric scales, self-assessment scales and comprehensive neurocognitive testing.ResultsWhile our preliminary results (n = 40) showed statistically significant improvement in various neurocognitive domains, including visuo-learning abilities, verbal learning, executive functions, attention and processing speed, initial impairment in semantic and phonetic fluency observed in acute psychosis remained unchanged in remission as well.ConclusionsAlthough our results showed improvement in most of cognitive domains during time, language abilities remained unchanged. This further confirms the hypothesis that language impairment is a trait marker of psychotic disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A complement-microglial axis drives synapse loss during virus-induced memory impairment.

Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae. Although thousands of cases of WNV-mediated memory dysfunction accrue annually, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development. Here we show that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model. Inoculation of WNV-NS5-E218A, a WNV with a mutant NS5(E218A) protein leads to survival rates and cognitive dysfunction that mirror human WNV neuroinvasive disease. WNV-NS5-E218A-recovered mice (recovery defined as survival after acute infection) display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning show increased expression of genes that drive synaptic remodelling by microglia via complement. C1QA was upregulated and localized to microglia, infected neurons and presynaptic terminals during WNV neuroinvasive disease. Murine and human WNV neuroinvasive disease post-mortem samples exhibit loss of hippocampal CA3 presynaptic terminals, and murine studies revealed microglial engulfment of presynaptic terminals during acute infection and after recovery. Mice with fewer microglia (Il34(-/-) mice with a deficiency in IL-34 production) or deficiency in complement C3 or C3a receptor were protected from WNV-induced synaptic terminal loss. Our study provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV neuroinvasive disease.

Early cognitive basic symptoms are accompanied by neurocognitive impairment in patients with an 'at-risk mental state' for psychosis.

Patients with an increased risk for psychosis ('at-risk mental state' (ARMS)) present various neurocognitive deficits. Not least because of differences in identifying the ARMS, results of previous studies are inconsistent. In most studies ARMS-patients are classified by the experience of attenuated psychotic symptoms (APS) and/or brief limited intermittent psychotic symptoms (BLIPS). Few studies additionally assessed cognitive basic symptoms (BS). A comprehensive assessment in the very early stage of the ARMS is missing. In the present study we characterized ARMS-patients for cognitive BS (ARMS-BS), APS and BLIPS (ARMS-A/B) according to the Early Recognition Inventory based on IRAOS (ERIraos). Furthermore, we assessed neurocognitive deficits using the MATRICS consensus cognitive battery for schizophrenia with a primary hypothesis regarding working memory performance. Groups of 38 ARMS-patients and 38 healthy controls were matched for age, gender, education and premorbid verbal intelligence. Between-group comparisons revealed significant poorer working memory performance in addition to lower verbal learning and problem solving, slower processing speed and lower global neurocognitive functioning in ARMS-patients as compared to controls. ARMS-BS did not differ from ARMS-A/B. These results underscore the presence of cognitive limitations in patients only presenting with cognitive BS. Knowledge of these early cognitive deviations supports the inclusion of early ARMS-stages into a comprehensive concept of the psychosis risk state. Therapeutic interventions already applied at this stage might prevent deterioration of constraints. Longitudinal and interventional studies investigating the interaction of cognitive BS and neurocognitive as well as metacognitive deficits are warranted.

NCO-12RELATIONSHIPS BETWEEN TUMOR COMPARTMENT VOLUMES AND NEUROCOGNITIVE FUNCTIONING IN PATIENTS WITH TEMPORAL LOBE GLIOMA

BACKGROUND: To determine whether tumor compartment volumes (necrosis, edema, non-enhancing and enhancing) derived from automated tumor segmentation are predictive of neurocognitive impairment in patients with temporal lobe glioma. METHODS: Treatment naive patients with glioma (n = 49; 67% glioblastoma; 74% left temporal) completed neurocognitive testing [WAIS-III Digit Span (DS); Controlled Oral Word Association (COWA); HVLT-R Total Recall; Trail Making Test A & B (TMT)]. Demographically-adjusted scores that were at or below -1.5 SDs were considered impaired. Presurgical T1, gadolinium-enhanced T1, T2, and FLAIR MRI were used to define 3D tumor boundaries. Using these sequences, 4 normalized tumor compartment volumes (necrosis; edema; non-enhancing; enhancing) were computed with an automated, validated, volumetric segmentation pipeline. Random Forest classifier in Waikato Environment for Knowledge Analysis software (WEKA) was used to predict the impairment for each neurocognitive test using different combinations of the volumetric compartments. RESULTS: Neurocognitive impairment was relatively common across measures [DS, 22%; COWA, 20%; TMT-A, 17%; TMT-B, 54%; HVLT-R Total Recall, 55%]. The gadolinium-enhancing compartment volume alone yielded the best classification accuracy for COWA [AUC = 0.72, TP = 82%, FP = 27%], HVLT-R Total Recall [AUC = 0.71, TP = 65%, FP = 37%], and TMT-A [AUC = 0.51, TP = 75%, FP = 65%]. Non-enhancing compartment volume alone was most predictive of DS [AUC = 0.71, TP = 74%, FP = 46%] and necrosis volume alone was most predictive of TMT-B [AUC = 0.66, TP = 63%, FP = 38%]. Including combinations of varying compartments did not convey predictive advantage over the single predictor models. CONCLUSION: Differing tumor compartment volumes were predictive of neurocognitive impairment across a variety of domains. Specifically, gadolinium-enhancing volume most accurately classified impairment in processing speed, verbal fluency, and verbal learning, non-enhancing volume best classified attentional impairment, and necrosis showed greatest accuracy for executive functioning. These findings suggest that relationships between tumor volume and neurocognitive functioning may vary by tumor compartment.

NCO-11TUMOR VOLUMETRIC AND TEXTURAL FEATURE PREDICTORS OF NEUROCOGNITIVE IMPAIRMENT IN PATIENTS WITH TEMPORAL LOBE GLIOMA

BACKGROUND: To determine whether computationally derived image-based textural and volumetric tumor features can predict cognitive impairment in patients with temporal lobe glioma. METHODS: Treatment naive patients with glioma (n = 69; 64% glioblastoma; 74% left temporal) completed neurocognitive testing [WAIS-III Digit Span (DS); Controlled Oral Word Association (COWA); HVLT-R Total Recall; Trail Making Test A & B (TMT)]. Demographically adjusted scores that were at or below 0.74). Volumetric and textural tumor features appear predictive of neurocognitive impairment in patients with glioma, with inclusion of textural indices conveying at least marginal improvement in classification accuracy.

Examination of the validity of the Brief Neurocognitive Assessment (BNA) for schizophrenia

BackgroundAlthough many comprehensive batteries exist to evaluate the nature and degree of cognitive impairments in patients with schizophrenia, short batteries hold promise for rapidly screening and estimating deficits in global cognition. Recently, the Brief Neurocognitive Assessment (BNA) was established and has been shown to have similar validity and utility to a more comprehensive battery of cognitive tests in evaluating global cognitive impairments in patients with schizophrenia. The present study sought to further establish the validity of the BNA by comparing it with the MATRICS Consensus Cognitive Battery (MCCB). MethodsOne-hundred seventy-six patients with schizophrenia and 300 healthy volunteers participated in the present study. Global cognition was evaluated using the MCCB composite score and estimated using the BNA. To examine practice effects and test–retest reliability, patients were re-assessed after 4weeks. ResultsThe BNA was highly correlated with global cognition as evaluated by the MCCB in both the schizophrenia (r=0.82) and healthy control samples (r=0.75). Both instruments were similarly sensitive to deficits in global cognition in patients with schizophrenia relative to healthy controls. The BNA also demonstrated high test–retest reliability in patients with schizophrenia (r=0.87), comparable to the level observed with the MCCB (r=0.91). In addition, both the BNA and MCCB showed a similar level of practice effects (both Cohen's d=0.11), and both instruments demonstrated equivalent sensitivities to longitudinal change. Furthermore, scores from the BNA and MCCB were related to symptom severity and functional capacity to a similar degree. ConclusionsThe BNA provides clinicians and researchers with an efficient and reliable means by which to evaluate global neurocognitive impairments in patients with schizophrenia by allowing estimation of performance on a more comprehensive standardized battery.

Neurocognitive impairment in corticosteroid-naive patients with active systemic lupus erythematosus: a prospective study.

Neurocognitive impairment (NCI) has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which may itself induce NCI. We investigated NCI in corticosteroid-naive people with SLE who did not exhibit any overt neuropsychiatric manifestations. Forty-three inpatients with SLE who had no current or past neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic characteristics were given a 1-h battery of neuropsychological tests. NCI was defined as scores at least 2 SD below the mean of the healthy control group on at least 2 of the 7 neurocognitive domains. Results of clinical, laboratory, and neurologic tests were compared regarding the presence of NCI. NCI was identified in 12 patients (27.9%) with SLE and in 2 control subjects (6.7%). Patients with SLE showed a significant impairment compared with controls on tasks assessing immediate recall, complex attention/executive function, and psychomotor speed. We identified psychomotor speed (Digit Symbol Substitution Test) as the factor that best differentiated the 2 groups. Further, we identified the score of the SLE Disease Activity Index 2000 as an independent risk factor for NCI in patients with SLE. We conclude that reduced psychomotor speed is an SLE-specific pattern of NCI. Verbal-memory deficits that have been reported in patients with SLE were not evident among patients who were corticosteroid-naive. Our results indicate that impaired psychomotor speed may be added to the symptoms of early SLE.

The MATRICS Consensus Cognitive Battery (MCCB): Performance and functional correlates

Neurocognitive impairment is a core feature in psychotic disorders and the MATRICS Consensus Cognitive Battery (MCCB) is now widely used to assess neurocognition in this group. The MATRICS has been translated into several languages, including Norwegian; although this version has yet to be investigated in an adult clinical population. Further, the relationship between the MATRICS and different measures of functioning needs examination. The purpose of this study was to describe neurocognition assessed with the Norwegian version of the MATRICS battery in a sample of patients with psychotic disorders compared to age and gender matched healthy controls and to examine the association with educational-, occupational- and social-functioning in the patient group. One hundred and thirty one patients and 137 healthy controls completed the battery. The Norwegian version of the MATRICS was sensitive to the magnitude of neurocognitive impairments in patients with psychotic disorders, with patients displaying significant impairments on all domains relative to healthy controls. Neurocognition was also related to both self-rated and objective functional measures such as social functioning, educational- and employment-history.

Computerized screening tools for neurocognitive impairment in patients with HIV infection

Neurocognitive impairment is one the non-infectious comorbidities related to HIV infection [1]. An increasing number of studies have shown the importance of assessing attention, motor, memory and cognitive functions under standardized conditions [2]. We have designed a computerized assessment tool, adapting some well-known methods of neurocognitive evaluation, and we have initiated a pilot study to assess the neurocognitive status of HIV-positive patients and controls. We assessed patients by applying the Motor Screening Task (MST: providing data on the sensorimotor function or comprehension), the Finger Tapping Test (FTT: motor function, self-directed manual motor speed), the Symbol Digit Test (SDT: divided attention, visual scanning, tracking and motor speed), and the Stroop Task (ST: selective attention and cognitive flexibility). All subjects were evaluated with this computerized set of tests during an appointment with the clinical psychologist. For statistical assessment, the T score was used. We assessed 10 HIV-positive patients and 15 controls. The median age and standard deviation were 26.5±11.5 years (range: 23-54) in the HIV group and 34±8 years (range: 25-53) in the control group. The MST scores were 720±131 ms and 629±79 ms in HIV vs. controls. The FTT scores were 167±24 ms and 163±12 ms in HIV vs. controls. The SDT scores were 6646±2905 ms and 2994±681 ms in HIV vs. controls. The ST scores were 689±92 ms, 1602±1009 ms and 2045±580 ms in the HIV group and 486±118 ms, 1041±244 ms and 1023±163 ms in the control group. Despite the low number of subjects included in the study, the T score showed a statistically significant difference between the two groups for MST, SDT, ST; no statistically significant difference was observed for FTT between the two groups. This pilot study has shown that in HIV-positive patients, the cognitive deficit tends to appear earlier than the motor one. Larger studies are needed to confirm these preliminary results and to provide more information on the clinical impact of this computerized tool for neurocognitive screening.

Perforin- and granulysin-mediated cytotoxicity and interleukin 15 play roles in neurocognitive impairment in patients with acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is an aggressive disease. The course of disease is regulated by pro-inflammatory agents, and malignant cell infiltration of tissues plays a deleterious role in disease progression, greatly impacting quality of life, especially in the cognitive domains. Our hypothesis is that significant serum concentrations of interleukin 15 (IL-15) are responsible for higher expression of adhesion molecules on endothelial cells of blood–brain barrier (BBB) which allow leukaemia cells and/or normal lymphocytes the infiltration into the brain. In brain tissue these cells could be stimulated to release perforin and granulysin causing induction of apoptosis in brain cells that are involved in complex neural signalling mediated by neurotransmitters, and consequent fine cognitive impairment. Such changes could be detected early, even before notable clinical psycho-neurological or radiological changes in patients with ALL. To evaluate this hypothesis we propose measuring cognitive function using Complex Reactiometer Drenovac (CRD) scores in patients with ALL. The expression of different adhesion molecules on BBB as well as presence and distribution of different lymphocytes in brain tissue will be analyzed. We will then correlate CRD scores with levels of IL-15 and the percentages of T cells, natural killer T cells, and natural killer cells expressing perforin and/or granulysin proteins. CRD is a scientifically recognised and highly sensitive psychometric laboratory test based on the complex chronometric mathematical measuring of speed of reaction to various stimuli. It provides an objective assessment of cognitive functions from the most complex mental activities to the simplest reaction reflexes. Early recognition of cognitive dysfunction might be important when selecting the most appropriate chemotherapy and/or radiotherapy regimens, and could allow for the implementation of preventive measures against further deterioration in cognitive function and quality of life in patients with ALL.

Neuropsychological assessment in HTLV-1 infection: Preliminary data of a comparative study among depression and neurocognitive impairments

The main goal of this present study was to investigate the presence of neurocognitive impairments in patients infected by HTLV-1 virus, associated with different levels of depression. 24 of the 150 patients regularly attending in the outpatient clinic of the HTLV at the Institute of Infectious Diseases Emilio Ribas, were evaluated by the team of neuropsychology and distributed into two groups, one with a degree of depression minimal / mild (n = 14) and another with moderate / severe (n = 10). 17 were female and 7 male, mean age 53.33 (SD = 11.9), average schooling 6.6 years (SD = 2.8), and 16 had HAM / TSP. The study delineation was observational and descriptive. The instruments used were the Beck Depression Inventory (BDI) to assess the depression state, plus a Neuropsychological Battery with the aim of assessing memory, language, and intellectual and motor functioning, attentional and executive functions. Data were analyzed by calculating averages, frequency and Spearman correlation (SPSS21v). The patients with higher levels of depression had worse performance on several cognitive domains. However, the neurocognitive deficits with statistical significance were found in tasks that assessed auditory memory post interference (p = 0.035) , sustained attention (p = 0.020) and motor speed (dominant hand = p = 0.02 / non-dominant hand p = 0.030). These preliminary data suggest that the neurocognitive performance may be related to the degree of depression and not solely the action of virus in the central nervous system.

8-Hydroxy-efavirenz, the Primary Metabolite of the Antiretroviral Drug Efavirenz, Stimulates the Glycolytic Flux in Cultured Rat Astrocytes

In active antiretroviral therapy antiretroviral drugs are employed for the restoration of a functional immune system in patients suffering from the acquired immunodeficiency syndrome. However, potential adverse effects of such compounds to brain cells are discussed in connection with the development of neurocognitive impairments in patients. To investigate potential effects of antiretroviral drugs on cell viability and the glycolytic flux of brain cells, astrocyte-rich primary cultures were exposed to various antiretroviral compounds, including the non-nucleoside reverse transcriptase inhibitor efavirenz. In a concentration of 10μM, neither efavirenz nor any of the other investigated antiretroviral compounds acutely compromised the cell viability nor altered glucose consumption or lactate production. In contrast, the primary metabolite of efavirenz, 8-hydroxy-efavirenz, stimulated the glycolytic flux in viable astrocytes in a time- and concentration-dependent manner with half-maximal and maximal effects at concentrations of 5 and 10μM, respectively. The stimulation of glycolytic flux by 8-hydroxy-efavirenz was not additive to that obtained for astrocytes that were treated with the respiratory chain inhibitor rotenone and was abolished by removal of extracellular 8-hydroxy-efavirenz. In a concentration of 10μM, 8-hydroxy-efavirenz and efavirenz did not affect mitochondrial respiration, while both compounds lowered in a concentration of 60μM significantly the oxygen consumption by mitochondria that had been isolated form cultured astrocytes, suggesting that the stimulation of glycolytic flux by 8-hydroxy-efavrienz is not caused by direct inhibition of respiration. The observed alteration of astrocytic glucose metabolism by 8-hydroxy-efavirenz could contribute to the adverse neurological side effects reported for patients that are chronically treated with efavirenz-containing medications.

Neurocognitive Impairment in Patients Treated with Protease Inhibitor Monotherapy or Triple Drug Antiretroviral Therapy

BackgroundIn patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.MethodsIn this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.ResultsOf the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15).ConclusionsCompared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.