Differences In Neurocognitive Functioning Research Articles

A-089 The Role of Anxiety Severity and Neurocognitive Functions in Parkinson’s Disease

Abstract Objective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. While much of the extant literature on neuropsychiatric symptoms and cognitive deficits have focused on depression, comparatively less have examined the role of anxiety among patients with PD. Here, we examined levels of anxiety severity (i.e., minimal, mild, moderate–severe) and cognition in this population. Method Fifty-six PD patients (M age = 60.8 ± 9.3; 69.6% male) being considered for surgical intervention were evaluated at an outpatient clinic. Inclusion criteria included no history of neurosurgical procedure and no other diagnosis of a neurodegenerative disorder. Participants completed a battery of neuropsychological tests and reported mood symptoms (Geriatric Depression Scale-15, Beck Anxiety Inventory). Those who scored above clinical cutoffs for depressive symptoms were excluded due to high comorbidity with anxiety. Motor symptom severity was rated by neurologists using the Unified Parkinson’s Disease Rating Scale. Results Analysis of covariance revealed significant group differences on tests of working memory (p = .03), set-shifting (p = .04), problem-solving (p = .05), and phonemic fluency (p = .03) when controlling for motor symptom severity. PD patients with moderate–severe levels of anxiety performed significantly lower than those with minimal or mild anxiety (p’s < .05). There were no other significant group differences in neuropsychological test performance. Conclusions These findings suggest measurable differences in neurocognitive functions associated with frontostriatal circuits among PD patients with varying levels of overall anxiety. Future work should consider the potential overlap between anxiety and PD symptoms as they relate to cognition.

A-34 Sex and Sport Differences in Baseline Neurocognitive Performance in Division-I Collegiate Athletes using the NIH Toolbox® Cognition Battery

Abstract Objective Understanding sex and sport-related differences in baseline neurocognitive scores may aid in interpreting post-injury performance. Sex and sport-related differences in neurocognitive performance for collegiate athletes have not been examined on the NIH Toolbox® Cognition Battery (NIHTB-CB). Therefore, this study sought to determine if baseline scores on the NIHTB-CB differ between sex or sport in collegiate athletes. It was hypothesized that sex, but not sport-related differences would exist in CB baseline performance. Method 107 Division-I athletes (47 females, 60 males) that participated in soccer (n = 45), football (n = 30), or cheerleading (n = 32) volunteered to participate. Participants completed tablet-based NIHTB-CB assessments including the Flanker Inhibitory Control & Attention (FICA), Dimensional Change Card Sort (DCCS), Picture Sequence Memory (PSM), and Pattern Comparison Processing Speed (PCPS) tests. These assessments measured visual attention, cognitive flexibility, memory recall, and processing speed, respectively. Fully corrected t-scores were used for analyses. Parametric and non-parametric tests compared scores based on sex and sport. Results Females demonstrated greater performance on the PCPS (Females: 64.72 ± 9.84, Males: 61.08 ± 8.85; p = 0.006). Males exhibited better performance on the FICA (Females: 45.72 ± 10.12, Males: 51.03 ± 10.70; p = 0.009). After controlling for sex, a significant difference across sports was identified in the FICA (p = 0.007) with cheerleading (43.81 ± 9.28) exhibiting poorer performance than football (54.33 ± 10.44; p = 0.002) and soccer (48.42 ± 10.28; p = 0.047). No sex or sport differences were identified for the DCCS or PSM. Conclusions Baseline differences in neurocognitive performance exist on the NIHTB-CB based on sex and sport suggesting these variables be taken into consideration when interpreting post-concussion scores in collegiate athletes.

S96. EXAMINING DIFFERENCES BETWEEN CURRENT CANNABIS CONSUMPTION AND COGNITIVE FUNCTIONING OF FIRST-EPISODE PSYCHOSIS PATIENTS: A RETROSPECTIVE STUDY

BackgroundAlthough growing research has observed a positive association between cannabis consumption and cognition in patients with first-episode psychosis (FEP), such better performance has not always been found across all cognitive domains. Furthermore, it remains unclear whether frequency of use is related to cognitive functioning in a dose-dependent manner. Understanding these associations may help to better manage cognitive impairments highly prevalent in FEP patients and inform prognosis. The aim of this study was to compare current cannabis use and cognitive functioning of FEP patients in a naturalistic setting. We hypothesized that FEP patients with current cannabis consumption (for the past 6 months or more) would present with higher cognitive performance scores compared to patients with no current consumption.MethodsThis cross-sectional, retrospective study included 192 current cannabis-using and 137 non-using patients at time of admission to a specialized early intervention clinic for FEP at the Douglas Mental Health University Institute in Montreal, Canada. Participants completed clinical and cognitive test batteries, including assessments of verbal memory, executive functioning, processing speed, working memory, attention, and visual memory. Cognitive domains were assessed using Weschler Memory Scale III and CogState Battery. Current cannabis consumption and frequency of use were assessed using the Chemical Use, Abuse, and Dependence Scale (CUAD). In addition to comparing status of cannabis consumption, four groups of FEP patients were analyzed according to frequency of use: 1) non-users (NU, n = 102), 2) light-users (LU, n = 21), 3) moderate-users (MU, n = 35), and heavy-users (HU, n = 64). Separate MANCOVA analyses were conducted to test the main effects of 1) current cannabis consumption (use vs non-use) and 2) frequency of cannabis use (none, light-use, moderate use, heavy use) on six cognitive domain performance scores. Age, sex, cigarette use, and cognitive battery type were entered as covariates, as they are known to influence neurocognitive scores.ResultsBetween-group comparisons on demographic variables revealed statistically significant differences in age (with NU being older than LU) and cigarette use (with the HU having higher % of use). Contrary to our hypothesis, no significant differences were found between current users and non-users, even while controlling for potential confounds, F(6,143) =1.61, p=.149. When splitting the user group based on frequency of use, no significant differences were observed on cognitive performance, F(18,399.3) =.903, p=.575.DiscussionOur findings reveal no significant differences between current cannabis consumption and cognitive functioning in a large representative sample of FEP patients at time of entry into a treatment clinic. This is consistent with previous studies that showed absence of differences in neurocognitive functioning between FEP cannabis users and non-users (e.g., Bugra et al., 2013). Other potential confounds such as the age of cannabis use onset, history of use and the different types of cannabis preparations may influence the present results and necessitate measurement in future investigations. The age differences observed may suggest that those who develop psychosis at a later age could be less predisposed to use cannabis. Alternatively, it is possible that light-use of cannabis somehow triggers the onset of psychosis, as is suggested by the literature that cannabis use is a component cause of developing psychosis.

REM Sleep Behavior Disorder in Parkinson's Disease: Effects on Cognitive, Psychiatric, and Functional outcomes.

Rapid eye movement sleep behavior disorder (RBD) affects 33-46% of patients with Parkinson's disease (PD) and may be a risk factor for neuropsychological and functional deficits. However, the role of RBD on neuropsychological functioning in PD has yet to be fully determined. We, therefore, examined differences in neurocognitive performance, functional capacity, and psychiatric symptoms among nondemented PD patients with probable RBD (PD/pRBD+) and without (PD/pRBD-), and healthy comparison participants (HC). Totally, 172 participants (58 PD/pRBD+; 65 PD/pRBD-; 49 HC) completed an RBD sleep questionnaire, psychiatric/clinical questionnaires, performance-based and self-reported functional capacity measures, and underwent a comprehensive neuropsychological battery assessing attention/working memory, language, visuospatial function, verbal and visual learning and memory, and executive function. Controlling for psychiatric symptom severity, the PD/pRBD+ group had poorer executive functioning and learning performance than the PD/pRBD- group and poorer neuropsychological functioning across all individual cognitive domains than the HCs. In contrast, PD/pRBD- patients had significantly lower scores than HCs only in the language domain. Moreover, PD/pRBD+ patients demonstrated significantly poorer medication management skills compared to HCs. Both PD groups reported greater depressive and anxiety severity compared to HCs; PD/pRBD+ group also endorsed greater severity of apathy compared to HCs. The presence of pRBD is associated with poorer neuropsychological functioning in PD such that PD patients with pRBD have poorer cognitive, functional, and emotional outcomes compared to HC participants and/or PD patients without pRBD. Our findings underscore the importance of RBD assessment for improved detection and treatment of neuropsychological deficits (e.g., targeted cognitive interventions).

Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)

AimsThe TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. MethodsBlinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. DiscussionThe TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient’s outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors’ neurocognitive function and societal participation.

Sex differences in cognitive functioning of patients at-risk for psychosis and healthy controls: Results from the European Gene-Environment Interactions study.

Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC. The data analyzed in this study were collected within the multicenter European Gene-Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group). Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC. Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.

Difference in Cognitive Function by First Onset Age of Alcohol Induced Blackout and Its Duration.

ObjectiveAlcohol-induced blackout (blackout) is a typical early symptom of cognitive impairment caused by drinking. However, the first onset age of blackout or the duration after onset of blackout has not been directly compared in previous studies. The purpose of this study was to investigate the differences in cognitive function to the first start age of blackouts and their duration.MethodsThirty-one male subjects were included in this study. Their age at the first blackout and the duration after the onset of blackout were investigated. Neuropsychological tests were conducted to determine their attention, memory, and executive function. Subjects were divided into three groups according to their age of the first onset blackout (group O1, < 20 years; group O2, 21–39 years; and group O3, > 40 years). Subjects were also divided into three groups by duration after the onset of blackout (P1, < 10 years; P2, 10–29 years; and P3, > 30 years). We then examined differences in neurocognitive function among these groups.ResultsO1 tended to have a lower memory score than O2 (F = 3.28, p = 0.053). Significant differences were observed in attention and executive function between groups P1 and P3 (Digit Span_backward: F = 6.07, p < 0.05; visual span_forward: F = 4.19, p < 0.05; executive intelligence quotient: F = 3.55, p < 0.05).ConclusionGreater memory impairment was detected in subjects having an earlier age of the first blackout. The longer the duration after the onset of blackout, the more impaired their attention and executive function skills.

Differences in neurocognitive performance and metabolic and inflammatory indices in male adults with obesity as a function of regular exercise.

What is the central question of this study? Does regular exercise have benefits with regard to the neurocognitive problems related to obesity and are regular-exercise-induced neurocognitive changes associated with changes in the levels of metabolic/inflammatory biomarkers? What is the main finding and its importance? Although obese individuals with regular exercise showed higher C-reactive protein levels as compared to the healthy-weight individuals, only the obese individuals with a sedentary lifestyle showed deviant neurocognitive performance and higher metabolic and tumour necrosis factor-α levels. The P3 amplitude was correlated with the levels of leptin in the obese individuals with regular activity, implicating that the potential mechanism of neurocognitive facilitation as a result of regular exercise could be reduced serum leptin levels. Obesity has been shown to be highly associated with deterioration in executive functions, elevated energy metabolic indices and low-grade systemic inflammation. Exercise has the capacity to reduce these negative phenomena. This work examined the effect of regular exercise on neurocognitive deficits and metabolic/inflammatory markers in obesity. Fifty-four participants were divided into three groups: healthy-weight (HW), obesity with regular exercise (ORE) and obesity with sedentary lifestyle (OSL), according to their BMI and frequency of exercise. Dual-energy X-ray absorptiometry was applied to assess the whole-body composition of the participants. The assessment included neurocognitive measures during the Posner paradigm test and fasting blood measurements. Relative to the HW group, only the OSL group showed significantly longer reaction times and smaller P3 amplitudes, even when controlling for the cardiorespiratory fitness co-variable. Although the OSL group exhibited a greater N2 amplitude than the HW group, when controlling for cardiorespiratory fitness the difference between the two groups disappeared. The OSL group showed greater levels of metabolic indices (i.e. leptin, insulin and glucose) than the HW group. The three groups had comparable interleukin (IL)-1β and IL-6 levels. However, the ORE and OSL groups showed higher levels of C-reactive protein than the HW group. The OSL group exhibited higher tumour necrosis factor-α levels than the HW and ORE groups. P3 amplitude was negatively correlated with the levels of leptin in the ORE group. Individuals with obesity can still obtain advantages with regard to neurocognitive and metabolic/inflammatory indices through engaging in regular exercise, possibly due to reduced serum leptin levels.

Gender differences of neurocognitive functioning in patients with first-episode schizophrenia in China

AimsTo investigate the gender differences in neurocognitive functioning in patients with first-episode schizophrenia (FES) in China. MethodsA total of 449 Chinese patients with FES (210 males, 239 females) were included in this study. Participants’ psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Neurocognitive functioning was assessed by 10 neuropsychological tests from a battery. Neurocognitive test scores were converted to scale scores and t-scores using normative data from Chinese populations. ResultsMales were younger and less likely to be married, had an earlier age of illness onset and a longer duration of untreated psychosis (DUP), and scored higher on the PANSS negative, general and total scales than females. After controlling for potential confounders, females performed better than males in the verbal learning and memory domain (p=0.016). While most neurocognitive domains were correlated with PANSS negative scores for male patients with FES, for female patients with FES, negative associations were found between scores on the PANSS general subscales and neurocognitive domains. We also performed a case-control comparison with a group of patients with clinically stable schizophrenia (CSS) (n=60) who were matched by age, sex and education years with patients with FES (n=58). After controlling for potential confounders, no significant differences were found between patients with FES and patients with CSS in all neurocognitive domains. Female patients still performed better in the verbal learning and memory domain (t=2.14, p=0.034). No interaction effects of gender and disease were found. ConclusionsGender was an independent influence factor for the verbal learning and memory domain. Both female patients with first-episode schizophrenia and female patients with clinically stable schizophrenia performed better than male patients.

Sex Differences in Neurocognitive Function in Adults with HIV: Patterns, Predictors, and Mechanisms.

Sex differences in cognitive function are well documented yet few studies had adequate numbers of women and men living with HIV (WLWH; MLWH) to identify sex differences in neurocognitive impairment (NCI) and the factors contributing to NCI. Here, we review evidence that WLWH may be at greater risk for NCI. We conducted a systematic review of recent studies of NCI in WLWH versus MLWH. A power analysis showed that few HIV studies have sufficient power to address male/female differences in NCI but studies with adequate power find evidence of greater NCI in WLWH, particularly in the domains of memory, speed of information processing, and motor function. Sex is an important determinant of NCI in HIV, and may relate to male/female differences in cognitive reserve, comorbidities (mental health and substance use disorders), and biological factors (e.g., inflammation, hormonal, genetic).

The Role of Quality of Education in Neurocognitive Functioning in a Diverse Sample with Chronic Opioid Use Disorder

Abstract Objective Literacy is a proxy for quality of education (QoE) and mediates ethnicity-related differences in neurocognitive (NC) performance in some populations (Manly et al., 2002; Rivera Mindt et al., 2008). However, it is unknown whether this relationship exists in the context of chronic opioid use disorder (OUD). This study examined the role of ethnicity, QoE, opioid use severity, and depression in predicting NC performance in a diverse sample of persons with OUD. Participants and Method This cross-sectional study included 74 adults with OUD (Age M = 40.3 [SD = 10.5]; Education M = 11.3 [2.5]; 24% female; 68% Latinx and 32% Non-Latinx White [NLW]). All participants completed comprehensive NC testing and psychiatric/substance use questionnaires. Variables included ethnicity (Latinx vs. Non-Latinx White), years of education, QoE (Wide Range Achievement Test, Third Edition; WRAT-3 Reading Standard Scores), opioid use severity (high vs. low OAT dose), current depression (Beck Depression Inventory, Second Edition; BDI-II Total Score), and demographically-corrected NC T-scores were computed and used for average domain T-scores (e.g., learning, memory, verbal fluency, executive function). Bivariate and ANCOVA analyses were used to compare ethnic groups. Results There were no significant group differences on opioid use severity or current depression (p’s &amp;gt; .05). However, compared to the NLW group, the Latinx group had lower years of education (M = 10.9 [SD = 1.7] vs. M = 12.2 [SD = 3.5]; t[72)] = 2.1, p &amp;lt; .05), QoE (M = 83.1 [SD = 13.6] vs. M = 94.8 [SD = 9.4]; t[72] = 3.8, p &amp;lt; .001), executive functioning (M = 42.0 [SD = 6.5] vs. M = 45.8 [SD = 8.5]; t[72) = 2.1, p &amp;lt; .05), and learning (M = 32.2 [SD = 8.2] vs. M = 37.8 [SD = 8.7]; t[72)] = 2.7, p &amp;lt; .05), with medium to large effect sizes (Cohen’s d &amp;gt; .50). The overall effect of ethnicity became non-significant for executive functioning after accounting for QoE (F[2,70] = 10.0, p = .002) and years of education (F[2,70)] = 16.8, p &amp;lt; .001). Conclusions The current study found that accounting for years of education and QoE attenuates some differences in NC performance between Latinx and Non-Latinx participants. References Manly, J. J., Jacobs, D. M., Touradji, P., Small, S. A., &amp; Stern, Y. (2002). Reading level attenuates differences in neuropsychological test performance between African American and White elders. Journal of the International Neuropsychological Society, 8(3), 341-348. Mindt, M. R., Arentoft, A., Germano, K. K., D’Aquila, E., Scheiner, D., Pizzirusso, M., ... &amp; Gollan, T. H. (2008). Neuropsychological, cognitive, and theoretical considerations for evaluation of bilingual individuals. Neuropsychology review, 18(3), 255-268.

History of High Motion Sickness Susceptibility Predicts Vestibular Dysfunction Following Sport/Recreation-Related Concussion.

To compare vestibular dysfunction at 1 to 10 and 11 to 20 days following sport/recreation-related concussion (SRC) in athletes with and without history of motion sickness susceptibility. Secondary aims of this study were to investigate differences in neurocognitive performance and affective symptoms in these groups. Cross-sectional. Concussion Specialty Clinic. One hundred twenty-four adolescents and adults (82 males, 42 females) aged 14 to 26 (16.36 ± 2.10) years, diagnosed with SRC in the past 10 (4.56 ± 2.54) days; 47 participants composed the sample for quartile analyses. Motion sickness susceptibility questionnaire short form score. Computerized neurocognitive test scores, vestibular/oculomotor screening scores (VOMS), and symptom factor scores from a standardized concussion symptom inventory. There was no association between history of motion sickness susceptibility and VOMS scores (above or below clinical cutoff) at 1 to 10 days after injury, although at 11 to 20 days after injury there was an association between high motion sickness susceptibility and symptoms above clinical cutoff on 5 of the 6 VOMS items (P values 0.01-0.04). The high motion sickness group had more affective symptoms on the symptom inventory than the no motion sickness group (P = 0.002) at 1 to 10 days after injury. Groups did not differ on computerized neurocognitive testing (P = 0.11). Athletes with a preexisting history of motion sensitivity may exhibit more prolonged vestibular dysfunction following SRC, and may experience more affective symptoms early in recovery.

Multilevel Mapping of Sexual Dimorphism in Intrinsic Functional Brain Networks.

Differences in cognitive performance between males and females are well-described, most commonly in certain spatial and language tasks. Sex-related differences in cognition are relevant to the study of the neurotypical brain and to neuropsychiatric disorders, which exhibit prominent disparities in the incidence, prevalence and severity of symptoms between men and women. While structural dimorphism in the human brain is well-described, controversy exists regarding the existence and degree of sex-related differences in brain function. We analyzed resting-state functional MRI from 650 neurotypical young adults matched for age and sex to determine the degree of sexual dimorphism present in intrinsic functional networks. Multilevel modeling was pursued to create 8-, 24-, and 51-network models of whole-brain data to quantify sex-related effects in network activity with increasing resolution. We determined that sexual dimorphism is present in the majority of intrinsic brain networks and affects ∼0.5–2% of brain locations surveyed in the three whole-brain network models. It is particularly common in task-positive control networks and is pervasive among default mode networks. The size of sex-related effects varied by network but can be moderate or even large in size. Female > male effects were on average larger, but male > female effects spread across greater network territory. Using a novel methodology, we mapped dimorphic locations to meta-analytic association test maps derived from task fMRI, demonstrating that the neurocognitive footprint of intrinsic neural correlates is much larger in males. All results were replicated in a motion-matched sub-sample. Our findings argue that sex is an important biological variable in human brain function and suggest that observed differences in neurocognitive performance have identifiable intrinsic neural correlates.

The influence of differences in neurocognitive function on lower limb kinematics, kinetics, and muscle activity during an unanticipated cutting motion.

Background Neurocognitive function may be a risk factor for anterior cruciate ligament (ACL) injury by changing neuromuscular control such as muscle activities. However, the effect of differences in neurocognitive function on biomechanics and neuromuscular control related to ACL injury risk is not clear. The purpose of this study was to examine the effect of differences in neurocognitive function on biomechanics and neuromuscular control during an unanticipated side-step cutting motion. Method The subjects were 15 collegiate female athletes who were divided into two groups using the Symbol Digit Modalities Test (SDMT). The experimental task was an unanticipated side-step cutting motion from a 30 cm high box. We calculated joint angles and moments using a 3-dimensional motion analysis system from the dominant leg, and measured muscle activities using a surface electromyography. We calculated the co-contraction ratio (CCR) as relative muscle activity of the quadriceps to the hamstring. Results As a result, subjects with a lower SDMT score had significantly increased quadriceps activity before and after ground contact and decreased CCR only after ground contact. Conclusion In the lower SDMT score group, the quadriceps showed stronger muscle activity than the hamstring during an unanticipated side-step cutting motion. This dominant quadriceps muscle activity has been reported to increase the load on the ACL, and there was a possibility of increasing the risk of the ACL injury. Considering these factors, subjects with lower neurocognitive function could have a high risk of ACL injury due to alterations in muscle activities surrounding the knee.

Cognitive Function and Quality of Life in Vorinostat-Treated Patients after Matched Unrelated Donor Myeloablative Conditioning Hematopoietic Cell Transplantation

Myeloablative conditioning allogeneic hematopoietic cell transplantation (HCT) puts patients at greater risk for significant cognitive and quality of life decline compared with recipients of reduced-intensity conditioning or autologous HCT. Vorinostat, a histone deacetylase inhibitor, has been shown to have neuroprotective and neurorestorative effects in preclinical models of neurologic diseases. Thus, within the context of a myeloablative conditioning phase II clinical trial of vorinostat combined with tacrolimus and methotrexate for graft-versus-host disease prophylaxis, we conducted an ancillary study to evaluate feasibility of assessing associations between vorinostat and neurocognitive function and quality of life (ClinicalTrials.gov NCT02409134). Nine patients (mean age, 53 years; range, 36 to 66) underwent computerized neuropsychological testing (Cogstate) and completed surveys of mood (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), and quality of life (Functional Assessment of Cancer Therapy–General). Control cohorts from a separate concurrent longitudinal study (19 autologous and 18 allogeneic HCT patients, who matched the vorinostat patients on relevant medical and demographic variables) completed the same test battery. All allogeneic patients received busulfan-based myeloablative conditioning and were transplanted with HLA-matched unrelated donors. The total neurocognitive performance score of vorinostat patients did not change significantly across the study duration (ie, baseline, day 30, day 100, and day 160). Depression, anxiety, and quality of life also did not differ significantly across time. In univariate analyses (analysis of variance), vorinostat-treated patients showed no difference in neurocognitive function or quality of life compared with autologous and allogeneic control subjects. However, when medical variables were accounted for in a linear mixed effects regression model, the total neurocognitive performance of vorinostat-treated patients was comparable with autologous control subjects. Notably, autologous control subjects performed significantly better than allogeneic control subjects (estimate, .64; standard error, .23; P ≤ .01). Moreover, a smaller percentage of vorinostat-treated patients were classified as mildly, moderately, or severely impaired across neurocognitive domains as well as time points compared with both control cohorts. Thus, vorinostat may have neurorestorative or neuroprotective effects in the HCT setting. Accordingly, we recognize the need for a future, full-scale randomized controlled trial to further examine this hypothesis.

Neurocognitive and Health Correlates of Overweight and Obesity among Ten-Year-Old Children Born Extremely Preterm

To assess the relationship between overweight (body mass index [BMI] percentile ≥85 and <95) and obesity (BMI ≥95 percentile) and developmental and health outcomes at 10 years of age in a cohort of individuals born extremely preterm. This was an observational cohort study of children born extremely preterm and then assessed at age 10 years for neurocognitive function and parent-reported behavior and health outcomes. Participants included 871 children aged 10 years. To describe the strength of association between overweight or obesity and outcomes, we used logistic regression models adjusting for confounders. Neurocognitive function, academic achievement, parent-reported health outcome surveys, and height and weight were measured. BMI category at 10 years of age was not associated with differences in intelligence, language, or academic achievement. Parents of children with obesity were more likely to report their child had asthma (OR 2.2; 95% CI 1.4-3.5), fair/poor general health (OR 3.2; 95% CI 1.4-7.5), and decreased physical function (OR 1.7; 95% CI 1.1-2.9) but less likely to have physician diagnosed attention-deficit/hyperactivity disorder (OR 0.5; 95% CI 0.3-0.97) or an individualized education plan (OR 0.6; 95% CI 0.4-0.99). Among children born extremely preterm, an elevated BMI, compared with normal or low BMI, is not associated with a difference in neurocognitive function. However, asthma, fair/poor general health, and decreased physical function were more prevalent among study participants with obesity, and attention-deficit/hyperactivity disorder and individualized education plan were less prevalent.

Effectiveness of temozolomide combined with whole brain radiotherapy for non-small cell lung cancer brain metastases.

BackgroundWe performed a retrospective analysis to compare the efficacy of whole brain radiotherapy (WBRT) combined with temozolomide (TMZ) versus WBRT alone as first‐line treatment for brain metastases (BM).MethodsSeventy‐eight non‐small cell lung cancer patients with BM were observed, including 45 patients who received WBRT plus TMZ (TMZ + WBRT) and 33 patients who received WBRT alone (WBRT). The primary outcome was overall survival (OS). Secondary outcomes included progression‐free survival (PFS), objective response rate (ORR), and adverse events.ResultsThe TMZ + WBRT arm achieved significant improvement in ORR (P = 0.0108) compared to the WBRT arm. PFS in the TMZ + WBRT arm was significantly longer than in the RT arm (6.0 vs. 3.5 months; P = 0.038). OS was not significantly different between the two arms. Although increased adverse reactions were experienced in the TMZ + WBRT arm, patients were tolerant of the side effects. Statistically significant differences in neurocognitive function and quality of life were observed between the arms at six months.ConclusionConcomitant TMZ + WBRT compared to WBRT alone significantly increases ORR and median PFS in patients with BM, but no remarkable difference in median OS was found. Adding TMZ to the treatment strategy could prevent neurocognitive function and quality of life from deteriorating. Although the addition of TMZ increases the incidence of adverse effects, no significant difference was observed. Thus, TMZ is safe and effective.

Effects of Developmental Age on Symptom Reporting and Neurocognitive Performance in Youth After Sports-Related Concussion Compared to Control Athletes.

There is increased necessity to focus research on school-aged athletes with sports-related concussion (SRC). This study assessed differences in symptom reporting and neurocognitive performance in youth athletes who sustained a sports-related concussion. A total of 1345 concussed and 3529 nonconcussed athletes (ages 8-21) completed the Immediate Post-concussive Assessment and Cognitive Testing (ImPACT). Analyses of covariance were conducted in order to assess differences in neurocognitive performance and symptom reporting between the sports-related concussion and control groups across age ranges. Longitudinal hierarchical linear modeling was employed to examine age and its relationship with rates of sports-related concussion recovery in neurocognitive performance. Results revealed athletes aged 13 to 15 had significantly lower neurocognitive performance scores compared to same-aged athletes without a history of sports-related concussion. With respect to the hierarchical linear modeling results, age was identified as a unique predictor of symptom recovery, particularly for ages 8 to 12. Results provide a better understanding of typical symptom reporting and neurocognitive outcomes for younger athletes across different ages.

Parasympathetic and sympathetic activity are associated with individual differences in neural indices of selective attention in adults

Multiple theoretical frameworks posit that interactions between the autonomic nervous system and higher-order neural networks are crucial for cognitive and emotion regulation. However, few studies have directly examined the relationship between measures of autonomic physiology and brain activity during cognitive tasks, and fewer studies have examined both the parasympathetic and sympathetic autonomic branches when doing so. Here, 93 adults completed an ERP auditory selective attention task concurrently with measures of parasympathetic activity (high-frequency heart rate variability; HF-HRV) and sympathetic activity (preejection period; PEP). We focus on the well-studied N1 ERP component to test for associations with baseline values of HF-HRV and PEP. Individuals with higher resting HF-HRV and shorter resting PEP showed larger effects of selective attention on their ERPs. Follow-up regression models demonstrated that HF-HRV and PEP accounted for unique variance in selective attention effects on N1 mean amplitude. These results are consistent with the neurovisceral integration model, such that greater parasympathetic activity is a marker of increased selective attention, as well as other theoretical models that emphasize the role of heightened sympathetic activity in more efficient attention-related processing. The present findings highlight the importance of autonomic physiology in the study of individual differences in neurocognitive function and, given the foundational role of selective attention across cognitive domains, suggest that both parasympathetic and sympathetic activity may be key to understanding variability in brain function across a variety of cognitive tasks.

S80. NEUROCOGNITIVE FUNCTIONING IN YOUTH AT RISK OF SERIOUS MENTAL ILLNESS

BackgroundNeurocognitive deficits are associated with many serious mental illnesses (SMI), including schizophrenia, bipolar disorder, and major depressive disorder, and have been found to negatively impact social and occupational outcomes, clinical prognosis, and overall quality of life. These deficits have also been observed in people in earlier phases of schizophrenia, specifically in young people at clinical high risk (CHR) of psychosis. In these youth, neurocognitive deficits present at a level intermediate to healthy controls and those with early psychosis, indicating that mild impairments in neurocognitive functioning may be early markers of illness development. It is possible that neurocognitive deficits may be present in young people at risk of a range of SMI beyond the psychosis-spectrum, including affective and anxiety disorders. The aim of this study was to compare neurocognitive functioning in a sample of youth at risk of SMI across the different clinical stages described by McGorry and colleagues and compare them to healthy controls (HCs). It was hypothesized that participants in the later stages of risk, characterized by the presence of subthreshold psychiatric symptoms or attenuated syndromes, would exhibit impairments in neurocognitive performance compared to HCs and asymptomatic youth at familial high risk.MethodsThis was an observational, cross-sectional study of 243 male and female individuals between the ages of 12–26. The sample consists of participants in the Canadian Psychiatric Risk and Outcome Study (PROCAN) and included: asymptomatic participants at familial high risk for SMI (Stage 0; n=41); youth with early mood or anxiety symptoms (Stage 1a; n=52); youth with attenuated psychotic or affective syndromes and distress (Stages 1b; n=108); and HCs (n=42). The neurocognitive battery included the WRAT-4 reading task, WASI Vocabulary and WASI Matrix Reasoning tasks, and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). All neurocognitive tasks were administered at baseline. Group differences in neurocognitive performance were analyzed using MANCOVA/ANCOVA analyses. Covariates included age and sex.ResultsSubjects in Stage 0 and Stage 1a did not significantly differ from any group. Subjects in Stage 1b (attenuated syndromes) had significantly lower neurocognitive scores in the domains of speed of processing, working memory, attention/vigilance and reasoning and problem solving, and on composite scores of neurocognitive performance and full-scale IQ compared to HCs. A secondary analysis demonstrated that subjects in Stage 1b who met CHR status according to Criteria of Psychosis-risk Syndromes (n=83) had lower scores in the domains of working memory, verbal learning, and reasoning and problem solving and on the overall composite score than the other participants in Stage 1b who did not meet CHR criteria.DiscussionThis study provides evidence for a growing literature which suggests that neurocognitive deficits may be markers of susceptibility for SMI development. It also increases what is known about neurocognitive performance associated with different stages of risk for SMI. Identification of such impairments could aid with detection of early mental health problems prior to illness onset.