Repeatable Battery Of Neuropsychological Status Research Articles

Peripheral and Central Nervous System Immune Effects of Bacillus Calmette‐Guérin (BCG) Vaccination in older adults with and without cognitive impairment

AbstractBackgroundThe live‐attenuated vaccine Bacillus Calmette‐Guérin (BCG), is widely used for the prevention of tuberculosis, and has myriad non‐specific beneficial effects in T1DM, multiple sclerosis, decreasing all‐cause childhood mortality, etc. Alzheimer’s Disease (AD) is a complex neurological disease. The innate immune system, intimately involved in the early and late phases of AD, may prove an ideal target for mono‐ or multi‐pronged therapy against AD. Data from multiple population health studies find that BCG treatment for bladder cancer is linked with decreased incidence of AD. Preclinical data also supports an AD‐beneficial effect of the vaccine. While mechanisms of some of these non‐specific vaccine effects have been elucidated, the mechanism behind BCG’s putative central nervous system (CNS) benefits is unclear. Here, we conducted a pilot open‐label study of the BCG (Tokyo strain) in the older adults to study CNS beneficial effects, particularly as they pertain to AD.MethodsBaseline measures of participants (N = 16) with or without mild cognitive impairment (MCI) included cognitive and neuropsychological testing, phlebotomy, and lumbar puncture (LP), followed by an initial intradermal BCG, with a booster given 1mo later. Neuropsychological testing, phlebotomy and LP were repeated at 3mo, 6mo (no LP), and 12mo. The primary endpoints include 1) the safety of the vaccine in older adults and 2) target engagement. Secondary and exploratory endpoints include 1) functional, immunological, and AD‐related biomarker measures and 2) cognitive and neuropsychological effects.ResultsOur interim analysis demonstrated an overall improvement in repeatable battery for neuropsychological status (RBANS) total score index (TSI), notably in subsections of delayed recall, and visuospatial and constructional indices. Our results also show robust peripheral target engagement and the induction of trained immunity in the peripheral blood cells. We will further show the effects on various AD‐related biomarkers in plasma and cerebrospinal fluid.ConclusionThese findings support that the BCG vaccine is safe in older adults and may improve cognition (enrollment of a placebo control group is underway). A further study including subjects with MCI and AD is ongoing. Our interventional studies with BCG begin to explore whether this strategy of retraining the neuroimmune axis can prevent and/or treat AD.

0080 TBI Time Since Injury: A Comparison Model Between Sleep Efficiency and Neurocognitive Performance

Abstract Introduction MTBI remains on one of the most prevalently reported brain injuries. Previous studies have shown an association between sleep efficiency, performance, and neurocognitive outcome. Reported time-since-injury (TSI) has also shown an association with neurocognitive outcome measures, with some evidence suggesting neurocognitive status is significantly worse at 2 weeks post-injury. Here, we examined differences in self-reported sleep efficiency at various time points since injury among individuals who had sustained an mTBI in the preceding year. Methods 190 Participants [71 male, 119 female], age M=24.48, SD=6.80 (HC, n=39) and five mild TBI groups based on time post-injury, 2-weeks (2W, n=12), 1-month (1M, n=30), 3-months (3M, n=34), 6-months (6M, n=33), and 12-months (12M, n=40) post-injury. Participants completed a cross-sectional study at specific post-injury time points ranging from (2W, 1M, 3M, 6M, 12M). Participants completed comprehensive Repeatable Battery for Neuropsychological Status (RBANS) and were administered the Pittsburg Sleep Quality Index (PSQI) at the time of assessment. Here we analyzed the sleep efficiency subscale of the PSQI. Separate correlation analysis examined the association between sleep efficiency and the attention index for each TSI group. Results The ANOVA showed a main effect of TSI group, F(5,182) = 2.83, p=.017. Post Hoc comparisons with the LSD test showed that the 12M group had worse sleep ­efficiency than HC and 2W, 1M, and 3M but did not differ from 6M (p<.05). Separate correlations between sleep efficiency and the attention index of the RBANS for each TSI group showed a marginally significant association at 2W (r(10)=-.467, p=.063, one tailed), and statistically significant at 12M (r(38)=-.266, p=.049, one tailed), suggesting that worse sleep efficiency was associated with worse attention performance at those time points. Conclusion Sleep efficiency differs across the first year of recovery from mTBI. Notably, individuals in the 12M TSI group appear to have worse sleep efficiency than any other TSI group but did not differ from the 6M group. Sleep efficiency appears to be associated with attentional capacity at 2W and 12M timeframes. This suggests that interventions that focus on enhancing sleep in patients with mTBI may prove promising for facilitating recovery. Support (if any) W81XWH-12-1-0386

The Efficacy of Extended Metacognitive Training on Neurocognitive Function in Schizophrenia: A Randomized Controlled Trial.

The aim of this study was to evaluate the effect of metacognitive training (MCT) on improving the neurocognitive function of Chinese patients with schizophrenia. One hundred inpatients with schizophrenia were selected by regional group randomization and divided into the control (treated as usual, TAU) group (n = 50) and the TAU + MCT group (n = 50). In this study, a 10-module MCT was used and the intervention process lasted 30 days. Cognitive function was assessed blindly using the Repeatable Battery of Neuropsychological Status (RBANS) scale at baseline, 24 h post-treatment, and 12 weeks’ post-treatment. The differences between the total RBANS score and baseline (pre-test) for the post-test and 12-week-follow-up tests were used as the primary outcome, and the difference between the RBANS dimension scores and baseline (pre-test) were used as a secondary outcome in this study. The completion rate at follow-up was high in the TAU + MCT group (94%). Intention-to-treat analysis and per-protocol analysis showed a significant increase in total neurocognitive function scores and three-dimensional scores (delayed memory, visual breadth, and attention) in the TAU + MCT group immediately after the intervention and at the 12-week follow-up compared with baseline. This study provides support for the efficacy of 10 module MCT concerning neurocognition.

Sensitivity of the Preclinical Alzheimer's Cognitive Composite (PACC), PACC5, and Repeatable Battery for Neuropsychological Status (RBANS) to Amyloid Status in Preclinical Alzheimer's Disease -Atabecestat Phase 2b/3 EARLY Clinical Trial.

Cognitive composites commonly serve as primary outcomes in Alzheimer's disease (AD) secondary prevention trials. To evaluate the association between amyloid (Aβ) burden level (+/-) and performance on three separate composite endpoints: Preclinical Alzheimer's Cognitive Composite (PACC), PACC+Semantic Fluency (PACC5), and Repeatable Battery for Neuropsychological Status (RBANS). Screening data from the randomized, double-blind, placebo-controlled, phase 2b/3 atabecestat EARLY study in preclinical AD participants were used in this analysis. The EARLY study was conducted at 143 centers across 14 countries. 3,569 cognitively unimpaired older adults (Clinical Dementia Rating of 0; aged 60-85 years) screened for inclusion in the EARLY study with Aβ status and at least PACC or RBANS at screening were included. Participants were categorized as those with non-pathological Aβ levels (Aβ-, n=2,824) and those with pathological Aβ levels (Aβ+, n=745) based on florbetapir uptake or levels of cerebrospinal fluid Aβ1-42. Analysis of Covariance models controlling for age, sex, and education were used to examine the difference in PACC, PACC5, and RBANS between Aβ groups. Nonparametric bootstrap was used to compare sensitivity of composites to differentiate between Aβ status. Of 3,569 participants, 2,116 were women (59%); 3,006 were Caucasian (84%); mean (SD) age was 68.98 (5.28) years. Aβ+ participants performed worse versus Aβ- participants on all cognitive composites though the magnitude of the Aβ effect was generally small. The Aβ+/- effect size for the PACC (Cohen's d=-0.15) was significantly greater than the RBANS (d=-0.097) while the PACC5 effect size (d=-0.139) was numerically larger than the RBANS. When examining subscores from the composites, memory tests (i.e., Free and Cued Selective Reminding Test, Figure Recall) and speed of processing (i.e., Digit-Symbol/Coding on the PACC/RBANS) exhibited the largest Aβ+/- effect sizes. Cross-sectional relationships between Aβ and cognition among clinically unimpaired older adults are detectable on multi-domain cognitive composites but are relatively small in magnitude. The Aβ+/- group effect was statistically larger for PACC and marginally larger for PACC5 versus RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.

SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN (SUPERBRAIN) showed improvement in cognitive function mostly in individuals with nutritional improvement: Sub‐analysis of SUPERBRAIN results

AbstractBackgroundThe MIND diet (Mediterranean‐DASH Intervention for Neurodegenerative Delay) is reported to be effective in preventing dementia. As the number of older adults with dementia in Korea increases, intervention programs suitable for older adults with dementia are needed. Therefore, we developed a Korean multi‐domain dementia prevention program including nutrition, exercise, cognitive training, vascular disease prevention and motivation.MethodOne‐hundred fifty three participants aged 60‐79 years with at least 1 dementia risk factor were randomly assigned in a 1:1:1 ratio to the FMI (Facility‐based intervention), HMI (Home‐based intervention) and the control group. The nutrition education program consisted of 10 classes during 24 weeks: the FMI received 7 group sessions and 3 1:1 sessions, the HMI received 4 group sessions and 3 1:1 sessions with 3 times homework sessions. The NQ‐E (Nutrition Quotient for Elderly) and the MNA (Mini Nutritional Assessment) were used to evaluate nutritional status. The RBANS (Repeatable Battery for Neuropsychological Status) and the CCI (Cognitive Complaint Interview) were used to evaluate cognitive function.ResultA total of 136 people (36 males and 100 females) completed the program with an 11.1% dropout rate. The NQ‐E score (p=0.009) and the RBANS score (p=0.001) were significantly increased in the FMI (N=45) and HMI (N=49) compared to the control group (N=42) after the study. The changes in the MNA score and the CCI score did not differ significantly among groups. As a result of sub‐analysis with the changes in the NQ‐E score before and after the study, there was no significant difference in cognitive function indicators among three groups when there was no change or improvement in the NQ‐E score. On the other hand, for those whose NQ‐E score was improved, the RBANS scores of the FMI (N=32) and the HMI (N=37) were significantly increased compared to the control group (N=25) (FMI: 0wk 496.69 points, 24wk 510.41 points; HMI: 0wk 502.86 points, 24wk 519.86 points, p=0.024).ConclusionIn conclusion, nutritional intervention focused on the MIND diet as a part of a multi‐domain intervention had an effect on improving the nutritional status and cognitive function score in the high‐risk group of dementia.

Late-Onset Suicide: A Dementia Prodrome?

This study examined whether late-onset (versus early-onset) suicidal behavior is associated with worse cognition. Participants included 278 adults aged 50+ years (56 nonpsychiatric comparison group; 67 nonsuicidal depressed older adults; 63 depressed suicide ideators; and 44 late-onset (55+ years) and 48 early-onset suicide attempters (<55 years). Using a case-control design, this study examined group differences in global cognition, episodic memory, information processing speed, and executive functioning, assessed using the Repeatable Battery of Neuropsychological Status and the Trail Making Test from the Delis-Kaplan Executive Function System. Linear regression was used for data analyses. Both attempter groups displayed worse executive functioning than nonsuicidal depressed older adults. Late-onset attempters additionally displayed poorer global cognition and processing speed than nonsuicidal depressed older adults and poorer memory than early-onset attempters. Late-onset suicidal behavior is associated with worse performance in a broad range of cognitive domains, possibly reflective of a dementia prodrome.

Vitamin B12 and Folate Status in Cognitively Healthy Older Adults and Associations with Cognitive Performance

ObjectivesTo determine prevalence of vitamin B12 and folate deficiency and associations with cognitive performance in participants recruited for the Cognitive Health in Ageing Register: Investigational, Observational, and Trial Studies in Dementia Research: Prospective Readiness cOhort Study (CHARIOTPRO) SubStudy (CPRO-SS).DesignCross-sectional analysis of data collected in the screening phase for the CPRO-SS.SettingParticipants were recruited from the Chariot Register at Imperial College London comprising approximately 39,000 community dwelling volunteers.ParticipantsCommunity dwelling individuals aged 60–85 years with B vitamin biomarker measures available were included (n=1946). After medical history and other exclusions, 1347 cognitively healthy participants were included for analysis of cognitive data.MeasurementsCognitive status was assessed with the Repeatable Battery for Neuropsychological Status (RBANS). Assays included vitamin B12 and folate, followed by serum methylmalonic acid and homocysteine levels for those with low vitamin B12. Gender-specific linear regression analysis was performed for associations between cognition and biomarkers. Non-gender specific regression for groups graded by B vitamin deficiency severity were also performed.ResultsVitamin B12 deficiency (<148pmol/L) was found in 17.2% of individuals and folate deficiency (<10nmol/L) in 1% of our participants. Low vitamin B12 was associated with poorer memory (p<0.03) in men. A high BMI predicted poorer attention and visuospatial indices (p<0.05). A regression analysis by B12 level revealed associations with poorer attention (β −6.46; p=0.004) for the deficient group and with immediate memory (β −2.99; p=0.019) for those categorised as severely deficient.ConclusionOlder men and women are prone to vitamin B12 deficiency with associated subtle and different domain-specific disruptive effects in measures of memory and attention. Elevated homocysteine and methylmalonic acid contributed to poorer cognitive performance. Novel groups at particular risk of cognitive deficit were identified for future interventional studies in this field.

Cognitive function and health-related quality of life 1 year after acute brain injury: An observational study.

Cognitive impairment and reduced health-related quality of life (HRQoL) are well-established sequelae of critical illness. Studies on survivors of critical illness have found delirium to be a predictor of these conditions, but evidence regarding survivors of acute brain injury is sparse. We aimed to explore if delirium duration was associated with 1-year cognitive impairment and reduced HRQoL in patients with acute brain injury. Intensive care unit (ICU) delirium was assessed using the Intensive Care Delirium Screening Checklist. Cognitive status was assessed using the Repeatable Battery for Neuropsychological Status (RBANS) and HRQoL using the European Quality of Life 5-dimension questionnaire (EQ-5D). We used a multiple linear regression for testing the association of delirium duration with cognitive impairment and quality of life, respectively. Forty-seven survivors of acute brain injury participated in follow-up and 35 completed RBANS. Delirium was present in 39 of 47 (83%) with a median duration of 4days. Delirium duration did not predict cognitive impairment (95% CI -4.1 to 0.5) or lower HRQoL (95% CI -1.4 to 2.7). Moderate-to-severe cognitive impairment was present in 17 of 35 (49%) participants, and they had a mean EQ-5D health visual analogue scale of 70.9 vs 81.6 for the Danish age-matched norm. Our sample did not demonstrate an association between delirium and 1-year cognitive impairment or reduced HRQoL. Still, a large proportion of the participants were cognitively impaired, and their quality of life was lower compared to norm. Larger studies are necessary to explore these associations further.

0080 Daytime Sleepiness Correlates with Increased Gray Matter Volume in the Right Middle Temporal Gyrus in Healthy Young Individuals

Abstract Introduction Daytime sleepiness has been associated with some neuroimaging metrics, including altered functional connectivity within the default mode network and decreased gray matter volume (GMV) of the medial prefrontal cortex. Most prior studies, however, have focused on patients with sleep disorders or other pathologies. Here we examined the association between GMV and self-reported daytime sleepiness among a healthy group of young adults who reported no sleep-related problems. Methods Forty-five healthy adults (22 female; Mean Age=25.4, SD=5.6), who self-reported no history of sleep-related disorders or major medical conditions, completed the Epworth Sleepiness Scale (ESS), the Repeatable Battery for Neuropsychological Status (RBANS) and underwent high-resolution structural neuroimaging at 3T. Gray matter volumes were processed using standard procedures in SPM12. After controlling for age, sex, and intracranial volume, GMV was regressed against ESS scores. Results Greater ESS was associated with larger GMV within a cluster of voxels in the right middle temporal gyrus (MNI coordinates: 57, -9, -22; k=1344 voxels, p=.003, FWE cluster corrected). After controlling for ESS scores, larger GMV in this region was associated with poorer delayed memory performance (r=-.345, p=.022) and total neurocognitive performance on the RBANS (r=-.303, p=.046). Conclusion Greater daytime sleepiness in healthy normal sleepers was associated with greater GMV within a region of the right middle temporal gyrus. Greater volume of this region was also associated with poorer neuropsychological performance. Decreased GMV of this same region has previously been reported in patients with obstructive sleep apnea and insomnia, suggesting that it may be particularly sensitive to sleep disruption or may play a role in the etiology of sleep disorders, even among young individuals who deny any history of sleep-related dysfunction. Longitudinal work should focus on the potential of this region as a biomarker of vulnerability to sleep problems. Support

COGNITION AND LATE-LIFE SUICIDE: COGNITIVE PROFILES AMONG DEPRESSED SUICIDAL SUBGROUPS AS A FUNCTION OF MEDICAL SERIOUSNESS AND ONSET OF SUICIDAL BEHAVIOR

Introduction Depressed older adults are at high-risk for suicidal behavior (Pfeiffer et al., 2013, Vannoy et al., 2007) and for developing dementia (Kaup et al, 2016; Mizra et al., 2016). Executive dysfunction has been described across the life-span in suicide attempters (Keilp et al., 2013, Clark et al., 2011, Richards-Devantoy et al., 2012). However, few studies have explored the links between several domains of cognition and suicide risk in those with late-life depression and the extant evidence is equivocal at best (Conejero et al., 2018, Tu et al., 2018, Erlangsen et al., 2008). Suicidal behavior is heterogeneous, and it is unclear whether the medical seriousness (Beck et al., 1975) of the suicide attempt or whether the onset of first suicidal behavior (initiated earlier in life relative to late-life (60+ years)) relates differently to cognitive deficits. Methods This project uses a case-control design and includes 278 adults aged 50?years and older: 56 non-depressed controls (no life-time history of psychiatric disorder), 67 non-suicidal depressed older adults(no life-time history of suicide ideation or suicide attempt), 63 depressed suicide ideators, and 92 depressed adults with a history of suicide attempt. Analysis 1 examined cognitive profiles of low (n=52) vs. high-lethality (i.e., potentially fatal without medical intervention) (n=40) suicide attempters relative to non-suicidal depressed older adults and non-depressed controls. Analysis 2 examined cognitive profiles of those making their first suicide attempt prior to age 60 (early onset: n=66) and those making their first suicide attempt at or after age 60 (late-onset: n=26) relative to non-suicidal depressed older adults and non-depressed controls. Lethality of attempt was similarly distributed across early- and late-onset attempters. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D-17 minus the suicide item). Cognitive functioning was assessed using the Repeatable Battery of Neuropsychological Status (RBANS) and the Trail Making Test from the Delis Kaplan Executive Functioning System (D-KEFS). Linear mixed effects models were used for assessing group differences cognitive domains assessed using multiple subtests or trials (i.e., learning and memory) and linear regression was used for cognitive domains assessed using a single test (i.e., processing speed, executive functioning). Demographic covariates were used for all data analyses (i.e., age, sex, education). Analyses comparing suicidal subgroups with non-suicidal depressed older adults additionally adjusted for depression severity and lifetime history of anxiety and substance use disorders. Results High-lethality attempters performed worse than low-lethality attempters and non-depressed controls on measures of verbal memory (Linear mixed effects model; group x test interaction: F=1.997, p=0.03). On a measure of executive functioning, low- but not high-lethality attempters performed worse than non-suicidal depressed older adults (LL: Beta= -0.18, p=0.01; HL: Beta=-0.12, p=0.08) and non-depressed controls (LL: Beta=0.31, p Conclusions Cognitive profiles of older suicidal attempters varied based on the lethality of most lethal suicide attempt and age of first suicide attempt. Those with low-lethality and early-onset suicide attempts exhibited executive dysfunction relative to non-suicidal depressed older adults, in-line with previous findings indicating executive dysfunction as part of life-long suicide vulnerability factors. In contrast, late-onset attempters exhibited slower processing speed relative to non-suicidal depressed older adults, and high-lethality attempters performed worse on memory measures relative to low-lethality attempters, possibly indicating a dementia prodrome. This research was funded by: NIMH: R01 MH085651; VA VISN 4 MIRECC Advanced Research Fellowship, VA Office of Academic Affiliations

The Utility of the Repeatable Battery of Neuropsychological Status in Patients with Temporal and Non-temporal Lobe Epilepsy.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief neuropsychological battery that has been validated in the assessment of dementia and other clinical populations. The current study examines the utility of the RBANS in patients with epilepsy. Ninety-eight patients with epilepsy completed the RBANS as part of a more comprehensive neuropsychological evaluation. Performance on the RBANS was evaluated for patients with a diagnosis of temporal lobe epilepsy (TLE; n=51) and other epilepsy patients (non-TLE, n=47) in comparison to published norms. Multivariate analysis of variance compared group performances on RBANS indices. Rates of impairment were also compared across groups using cutoff scores of ≤1.0 and ≤1.5 standard deviations below the normative mean. Exploratory hierarchical regressions were used to examine the relations between epilepsy severity factors (i.e., age of onset, disease duration, and number of antiepileptic drugs [AEDs]) and RBANS performance. TLE and non-TLE patients performed below the normative sample across all RBANS indices. Those with TLE performed worse than non-TLE patients on the Immediate and Delayed Memory indices and exhibited higher rates of general cognitive impairment. Number of AEDs was the only epilepsy severity factor that significantly predicted RBANS total performance, accounting for 14% of the variance. These findings suggest that the RBANS has utility in evaluating cognition in patients with epilepsy and can differentiate TLE and non-TLE patients. Additionally, number of AEDs appears to be associated with global cognitive performance in adults with epilepsy.

Abstract 17: Cognitive, Psychological, and Functional Limitations After Sudden Cardiac Arrest Among a Racially and Ethnically Diverse United States Population

Background: To estimate the frequency of post-sudden cardiac arrest survivorship (PSCAS) problems (i.e., cognitive impairment, disability in activities of daily living, depression and posttraumatic stress disorder (PTSD)). Methods: We prospectively enrolled adults with return of spontaneous circulation after in-hospital or out-of-hospital CA between 9/2015-8/2018 at a high-volume, major academic center. A consecutive sample of survivors at hospital discharge and at one-year follow-up able to engage in the Repeatable Battery for Neuropsychological Status (RBANS) or Telephone Interview for Cognitive Status (TICS), Barthel Index (BI) as a measure of disability, Center for Epidemiological Studies Depression Scale (CES-D), and PTSD Checklist - Specific (PCL-S) were included. Results: Of 159 patients included, average age was 54±15 years, 41% were women, 30% identified themselves as Latinos and 18% as African-American. There were 14 deaths and 13 lost to follow-up at one-year. As shown in table 1, 1 out of 2 patients at discharge, and 1 out of 4 at one-year had global cognition scores similar to scores for patients with moderate traumatic brain injury and patients with mild Alzheimer’s disease, respectively. The majority had physical disability at hospital discharge, which showed improvement within one-year. A significant proportion of patients experienced depressive and PTSD symptoms at hospital discharge and the symptoms persisted at one-year. Conclusions: In a racial and ethnically diverse cohort in a major academic center in the US, one or more PSCAS problems were present and persisted in the majority of CA survivors, and co-occurring problems were present in one out of four at one-year. Future studies are needed to understand better the heterogeneous subtypes of PCAS and to identify modifiable risk factors and potential ameliorating factors. Table 1. Estimates of post-sudden cardiac arrest survivorship problems at discharge and one-year

Women have worse cognitive, functional, and psychiatric outcomes at hospital discharge after cardiac arrest

AimTo examine gender differences among cardiac arrest (CA) survivors’ cognitive, functional, and psychiatric outcomes at discharge. MethodsThis is a prospective, observational cohort of 187 CA patients admitted to Columbia University Medical Center, considered for Targeted Temperature Management (TTM), and survived to hospital discharge between September 2015 and July 2017. Patients with sufficient mental status at hospital discharge to engage in the Repeatable Battery for Neuropsychological Status (RBANS), Modified Lawton Physical Self-Maintenance Scale (M-PSMS), Cerebral Performance Category Scale (CPC), Center for Epidemiological Studies Depression Scale (CES-D), and Post-Traumatic Stress Disorder Checklist – Civilian Version (PCL-C) were included. Fisher’s exact, Wilcoxon Rank Sum, and regression analysis were utilized. Results80 patients (38% women, 44% white, mean age 53 ± 17 years) were included. No significant gender differences were found for age, race, Charlson Comorbidity Index, premorbid CPC or psychiatric diagnoses, arrest related variables, discharge CPC, or PCL-C scores. Women had significantly worse RBANS (64.9 vs 74.8, p = .01), M-PSMS (13.6 vs 10.6, p = .02), and CES-D (22.8 vs 14.3, p = .02) scores. These significant differences were maintained in multivariate models after adjusting for age, initial rhythm, time to return of spontaneous circulation, and TTM. ConclusionsWomen have worse cognitive, functional, and psychiatric outcomes at hospital discharge after cardiac arrest than men. Identifying factors contributing to these differences is of great importance in cardiac arrest outcomes research.

A Retrospective Study of Predictors of Return to Duty versus Medical Retirement in an Active Duty Military Population with Blast-Related Mild Traumatic Brain Injury.

Traumatic Brain Injury (TBI) has been described as the "signature injury" of the Global War on Terror. Explosive blast TBI has become a leading cause of injury as a result of the widespread use of improvised explosive devices in Iraq and Afghanistan. We present a retrospective cross-sectional study of patients with blast-related mild TBI (mTBI, N = 303) seen at the Intrepid Spirit Concussion Recovery Center at Naval Medical Center Camp Lejeune. The objective was to predict outcomes of return to duty (RTD) vs. medical retirement via medical evaluation board (MEB), based on brain imaging, neuropsychological data, and history of mTBI. The motivation is to inform prognosis and target resources to improve outcomes for service members who are less likely to RTD through the standard treatment program. The RTD was defined operationally as individuals who completed treatment and were not recommended for medical retirement or separation for TBI or related sequelae. Higher scores on the Repeatable Battery for Neuropsychological Status (RBANS) test were associated positively with RTD (p = 0.001). A history of three or more lifetime concussions was associated negatively with RTD, when compared with one concussion (p = 0.04). Elevated apparent diffusion coefficient (ADC) in the anterior corona radiata was associated negatively with RTD (p = 0.04). A logistic regression model was used to classify individuals with RBANS and imaging data (n = 81) as RTD or MEB according to RBANS, ADC, and a history of multiple (≥3) concussions. The RBANS (p = 0.003) and multiple concussions (p = 0.03) were significant terms in the logistic model, but ADC was not (p = 0.27). The area under the receiver operating characteristic curve was 0.77 (95% confidence interval 0.66-0.86). These results suggest cognitive testing and TBI history might be used to identify service members who are more likely to be retired medically from active duty.

Relationship between neuropsychological tests and driver's license renewal tests in Parkinson's disease

ABSTRACTObjective: To determine whether the standard Spanish driving test (ASDE test) was able to identify patients with Parkinson's disease (PD) at risk of unsafe driving and to examine the relationship between the ASDE test and the Useful Field of View (UFOV) as well as with a battery of neuropsychological tests in drivers with PD.Methods: Thirty-seven patients with PD and 33 controls matched by age and education level were included in an observational study. All participants were active drivers and patients with PD underwent study procedures after taking the medication in the “on” period. Subjects with a Mini-Mental State Examination (MMSE) score ≤ 24 were excluded. Neuropsychological tests (Repeatable Battery for Neuropsychological Status [RBANS], Trail Making Test [TMT-A and -B], and Block Design test), driving performance tests (ASDE Driver Test and UFOV), and daytime sleepiness (Epworth Sleepiness Scale) were assessed.Results: The PD group performed significantly worse than healthy controls in the ASDE Motor Coordination tests. No significant differences were observed in anticipation speed, multiple reaction time, concentrated attention, and resistance to monotony. All participants successfully completed the UFOV tests. Statistically significant differences between patients with PD and controls were found in processing speed (UFOV1; P =.03) and more patients with PD were found in the categories of higher driving risk levels (P =.03). In addition, patients with PD showed worse scores than healthy controls in visuospatial capacities (Line Orientation), psychomotor speed (Coding and TMT-A), memory (List Recognition, Story Recall), and executive function (TMT-B). The driving tests (ASDE and UFOV) showed a low sensitivity and a high specificity but a higher percentage of patients in the PD group failed in multiple reaction time, concentrated attention, and resistance to monotony. In addition, 18.9% of patients with PD showed a cutoff of 4 for UFOV risk. In the discriminant analysis, Line Orientation (visuospatial/constructive domain) and Figure Recall (delayed memory) were found to be statistically significant with a rate of correct classification of unsafe drivers with PD of 78.2%. In addition, normal results on the Line Orientation item were associated with a 1.5 times higher probability of non-risky driving in the multivariate analysis.Conclusions: At early stages of the disease, about 19% of patients with PD showed difficulties that may affect their driving capabilities. Line Orientation and Figure Recall are useful to alert clinicians to the risk of unsafe driving. For this reason, patients with PD should be evaluated for driving abilities more regularly to determine the extent of deficits that may influence driving performance.

Instructional influence on learning and decision making with respect to cognitive functioning

IntroductionHumans learn how to behave both through rules and instructions (explicit learning) as well as through environmental experiences (implicit learning). It has been shown that instructions can powerfully control people's choices, often leading to a confirmation bias.AimTo explore confirmation bias with respect to cognitive functioning in healthy adult participants.MethodsWe recruited 25 healthy adult control subjects (9 males, 16 females, age 31.40 ± 6.08 years). Participants completed Repeatable Battery of Neuropsychological Status (RBANSS) as well as Instructed Version of Probabilistic Selection Task (IPST) (Doll et al., 2009).ResultsBased on the performance on IPST into two groups: a group with higher and lower susceptibility to confirmation bias. We found no difference between these groups with respect to any of the cognitive domains measured with RBANSS (immediate memory, visuospatial abilities, language, attention and delayed memory) (U Mann-Whitney test, P &gt; 0.05).ConclusionIn healthy adults, susceptibility to confirmation bias is independent of cognitive functioning (immediate and delayed memory, visuospatial abilities, language and attention).Disclosure of interestThe authors have not supplied their declaration of competing interest.

Computational modeling of reinforcement learning using probabilistic selection task and instructional probabilistic selection task

IntroductionHumans learn how to behave both through rules and instructions as well as through environmental experiences. It has been shown that instructions can powerfully control people's choices, often leading to a confirmation bias.AimTo compare learning parameters in reinforcement learning task with and without instructions.MethodsWe recruited 52 healthy adult control subjects (21 males, 31 females, age 30 ± 6.5 years). Participants completed Repeatable Battery of Neuropsychological Status (RBANSS). Twenty-seven participants completed additionally Probabilistic Selection Task (PST) while twenty-five participants completed Instructional Probabilistic Selection Task (IPST). To analyze learning parameters, we used Q-learning model with 3 parameters: learning rate due to positive and negative reinforcements as well as exploration-exploitation parameter.ResultsBoth groups did not differ with respect to cognitive functioning measured with RBANSS (immediate and delayed memory, visuospatial abilities, language and attention); however, participants who completed PST had trend-level statistically faster learning rates due to positive (P = 0.099) and negative reinforcements (0.057) in comparison to participants who completed IPST. Both groups did not differ with respect to exploration-exploitation parameter (0.409).ConclusionIn healthy adults, interference of confirmation bias can influence learning speed independent of cognitive functioning (immediate and delayed memory, visuospatial abilities, language and attention).Disclosure of interestThe authors have not supplied their declaration of competing interest.

Altered metal metabolism in patients with HCV-related cirrhosis and hepatic encephalopathy.

Dysfunctional metal homeostasis contributes to oxidative stress and neuronal damage. These have been implicated in hepatic encephalopathy pathogenesis. To investigate whether altered metal metabolism is associated with hepatic encephalopathy. Twenty-one controls and 34 HCV-cirrhotic patients (ENC/NEC patients according to presence/absence of previous overt episodes of hepatic encephalopathy) and a control group were studied. Serum iron, copper, ceruloplasmin, ceruloplasmin activity, transferrin, and ceruloplasmin/transferrin ratio were determined. Neuropsychological tests were performed by the repeatable battery of neuropsychological status. Magnetic resonance assessed basal ganglia volumes and metal deposition (pallidal index and T2*). Cirrhotic patients performed worse than controls at cognitive tests, especially ENC patients,. At biochemical analysis copper concentrations, ceruloplasmin activity and transferrin levels were lower in ENC than in NEC patients and controls (p < 0.05 and p < 0.01, respectively). Ceruloplasmin/transferrin ratio was higher in ENC compared to NEC patients (p < 0.05), and controls (p < 0.01). By brain magnetic resonance, ENC patients showed reduced caudate and globus pallidus volumes compared to controls (p < 0.05), and ENC and NEC patients an increased pallidal index compared to controls (p < 0.01). In ENC patients, ceruloplasmin activity correlated with caudate volume and pallidal index (ρ = 0.773 and ρ = -0.683, p < 0.05). Altered metal metabolism likely contributes to cirrhotic hepatic encephalopathy.

Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age.

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean = 35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.

Openness to experience is related to better memory ability in older adults with questionable dementia

The personality traits Openness to experience and Neuroticism of the five-factor model have previously been associated with memory performance in nondemented older adults, but this relationship has not been investigated in samples with memory impairment. Our examination of 50 community-dwelling older adults (29 cognitively intact; 21 with questionable dementia as determined by the Clinical Dementia Rating Scale) showed that demographic variables (age, years of education, gender, and estimated premorbid IQ) and current depressive symptoms explained a significant amount of variance of Repeatable Battery of Neuropsychological Status Delayed Memory (adjusted R 2 = 0.23). After controlling for these variables, a measure of global cognitive status further explained a significant portion of variance in memory performance (ΔR2 = 0.13; adjusted R 2 = 0.36; p < .01). Finally, adding Openness to this hierarchical linear regression model explained a significant additional portion of variance (ΔR2 = 0.08; adjusted R 2 = 0.44; p < .01) but adding Neuroticism did not explain any additional variance. This significant relationship between Openness and better memory performance above and beyond one's cognitive status and demographic variables may suggest that a lifelong pattern of involvement in new cognitive activities could be preserved in old age or protect from memory decline. This study suggests that personality may be a powerful predictor of memory ability and clinically useful in this heterogeneous population.