Objective: To characterize cognitive function in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in comparison with other chronic conditions, and to investigate its association with disease activity, and other psychological factors. Methods: Cross-sectional study including patients with AAV, rheumatoid arthritis (RA) (n = 30), and chronic kidney disease (CKD) (n = 29). Patients underwent a standardized neuropsychological battery (NEUROPSI). Sleep quality, fatigue, depression, and anxiety levels were assessed. Results: A total of 60 patients with AAV were included, median age of 54 years, and disease duration of 5.6 years. Prevalence of cognitive dysfunction (CD) in AAV patients was similar to RA and CKD (35%, 40%, and 39.3%, respectively, p = .88). When AAV patients with (n = 21) and without (n = 39) CD were compared, significantly more patients with CD had high disease activity (67% vs. 31%, p = .009). Abnormal performance was more frequent in the executive functions in the three groups (45% AAV, 51.7% RA, and 50% CKD), followed by language (25%, 13.8%, and 25%, respectively). Verbal and visual attentional tests were more frequently impaired in patients from the CKD group (p = .021), and psychomotor functions were more frequently affected in AAV patients (p < .05). Hospital Anxiety and Depression Scale (HADS) total score (especially anxiety) was higher in patients with memory impairment than in those with normal memory function (M = 6.79, SD = 4.53 vs. M = 4.5, SD = 3.6, p < .01). Neither Sleep Quality Index nor fatigue scale scores differed between those cognitively impaired and not impaired. Conclusions: No statistically significant differences were found in the frequency of CD among the three clinical populations. (JINS, 2019, 25, 595–602)

Objectives: We conducted joint analyses from five randomized clinical trials (RCTs) of online family problem-solving therapy (OFPST) for children with traumatic brain injury (TBI) to identify child and parent outcomes most sensitive to OFPST and trajectories of recovery over time. Methods: We examined data from 359 children with complicated mild to severe TBI, aged 5–18, randomized to OFPST or a control condition. Using profile analyses, we examined group differences on parent-reported child (internalizing and externalizing behavior problems, executive function behaviors, social competence) and family outcomes (parental depression, psychological distress, family functioning, parent–child conflict). Results: We found a main effect for measure for both child and family outcomes [F(3, 731) = 7.35, p < .001; F(3, 532) = 4.79, p = .003, respectively], reflecting differing degrees of improvement across measures for both groups. Significant group-by-time interactions indicated that children and families in the OFPST group had fewer problems than controls at both 6 and 18 months post baseline [t(731) = −5.15, p < .001, and t(731) = −3.90, p = .002, respectively, for child outcomes; t(532) = −4.81, p < .001, and t(532) = −3.80, p < .001, respectively, for family outcomes]. Conclusions: The results suggest limited differences in the measures’ responsiveness to treatment while highlighting OFPST’s utility in improving both child behavior problems and parent/family functioning. Group differences were greatest at treatment completion and after extended time post treatment.

Objectives: Visual-spatial neglect is a common attentional disorder after right-hemisphere stroke and is associated with poor rehabilitation outcomes. The presence of neglect symptoms has been reported to vary across personal, peripersonal, and extrapersonal space. Currently, no measure is available to assess neglect severity equally across these spatial regions and may be missing subsets of symptoms or patients with neglect entirely. We sought to provide initial construct validity for a novel assessment tool that measures neglect symptoms equally for these spatial regions: the Halifax Visual Scanning Test (HVST). Methods: In Study I, the HVST was compared to conventional measures of neglect and functional outcome scores (wheelchair navigation) in 15 stroke inpatients and 14 healthy controls. In Study II, 19 additional controls were combined with the control data from Study I to establish cutoffs for impairment. Patterns of neglect in the stroke group were examined. Results: In Study I, performance on all HVST subtests were correlated with the majority of conventional subtests and wheelchair navigation outcomes. In Study II, neglect-related deficits in visual scanning showed dissociations across spatial regions. Four inpatients exhibited symptoms of neglect on the HVST that were not detected on conventional measures, one of which showed symptoms in personal and extrapersonal space exclusively. Conclusions: The HVST appears a useful measure of neglect symptoms in different spatial regions that may not be detected with conventional measures and that correlates with functional wheelchair performance. Preliminary control data are presented and further research to add to this normative database appears warranted. (JINS, 2019, 25, 490–500)

Objective: Concussion in children and adolescents is a prevalent problem with implications for subsequent physical, cognitive, behavioral, and psychological functioning, as well as quality of life. While these consequences warrant attention, most concussed children recover well. This study aimed to determine what pre-injury, demographic, and injury-related factors are associated with optimal outcome (“wellness”) after pediatric concussion. Method: A total of 311 children 6–18 years of age with concussion participated in a longitudinal, prospective cohort study. Pre-morbid conditions and acute injury variables, including post-concussive symptoms (PCS) and cognitive screening (Standardized Assessment of Concussion, SAC), were collected in the emergency department, and a neuropsychological assessment was performed at 4 and 12 weeks post-injury. Wellness, defined by the absence of PCS and cognitive inefficiency and the presence of good quality of life, was the main outcome. Stepwise logistic regression was performed using 19 predictor variables. Results: 41.5% and 52.2% of participants were classified as being well at 4 and 12 weeks post-injury, respectively. The final model indicated that children who were younger, who sustained sports/recreational injuries (vs. other types), who did not have a history of developmental problems, and who had better acute working memory (SAC concentration score) were significantly more likely to be well. Conclusions: Determining the variables associated with wellness after pediatric concussion has the potential to clarify which children are likely to show optimal recovery. Future work focusing on wellness and concussion should include appropriate control groups and document more extensively pre-injury and injury-related factors that could additionally contribute to wellness. (JINS, 2019, 25, 375–389)

Objectives: The aim of our study was to assess the differences in facial emotional recognition (FER) between patients with first-episode psychosis (FEP), patients with multi-episode schizophrenia (SCH), and healthy controls (HC) and to find possible correlations of FER with psychopathology in the two patient groups. Methods: We performed a cross-sectional study enrolling 160 patients from two psychiatric hospitals in Croatia (80 FEP and 80 SCH) and 80 HC during the period from October 2015 until October 2017. Patients were assessed once during their hospital treatment, using the Penn Emotion Recognition Task for assessment of FER, rating scales for psychopathology and depression and self-reporting questionnaires for impulsiveness, aggression, and quality of life. Results: The number of correctly identified emotions significantly decreased from HC to FEP [Δ −7%; 95% confidence interval (CI) [−12% to −3%], effect size r = 0.30] and more markedly in SCH (Δ −15%; 95% CI [−25% to −10%], effect size r = 0.59) after the adjustment for age and gender and correction for multiple testing. Correct FER for negative emotions, but not for happiness and neutral emotions, had a statistically significant negative correlation with some features on the scales of psychopathology, impulsivity and aggression in both patient groups. Conclusions: Impairment of FER is present from the first episode of schizophrenia and increases further with multiple psychotic episodes, but it may depend on or contribute to clinical symptoms. Therefore, assessment of FER should be included in the clinical assessment and integrated in the plan of treatment from the beginning of the illness. (JINS, 2019, 25, 165–173)

Objective: To examine trajectories of declines in learning and retention during the predementia phase of Alzheimer’s disease (AD) using the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR). Method: Learning was defined by the sum of free recall over three test trials. Retention was defined in two ways: by delayed free recall (DFR) and by savings; DFR adjusted for learning. The performances of 217 incident AD cases from the Baltimore Longitudinal Study of Aging (BLSA) were aligned based on the time that AD was first diagnosed. The predementia phase of learning and retention decline was assessed using change point models in which cognitive trajectories are described by a series of linear components with knots delineating times of accelerating decline. Results: Trajectories for both learning and DFR had two change points: the first at 6.58 (95% confidence intervals (CI): 6.56, 6.60) to 7.29 (95% CI: 6.13, 8.46) years before diagnosis followed by gradual decline over the next 4 years, and a second acceleration of decline 1.89 (0.56, 3.24) to 2.93 (95% CI: 1.56, 4.30) years before diagnosis. The change points for DFR were not significantly earlier in the predementia phase than the change points for learning. Savings had one change point, 5.3 (95% CI: 3.56, 7.04) years before diagnosis. Conclusion: Both learning and DFR showed similar profiles of decline in the years prior to the clinical diagnosis of AD. When delayed recall was adjusted for initial learning, the measure was less sensitive to early disease. (JINS, 2019, 25, 699–705)

Objectives: The aim of this study was to investigate the effects of infant and toddler head growth on intelligence scores from early childhood to adulthood in very preterm (<32 weeks gestational age; VP) and/or very low birth weight (<1500 g; VLBW) and term born individuals. Methods: 203 VP/VLBW and 198 term comparisons were studied from birth to adulthood as part of the prospective geographically defined Bavarian Longitudinal Study (BLS). Head circumference was assessed at birth; 5, 20 months; and 4 years of age. Intelligence was assessed with standardized tests in childhood (6 and 8 years: K-ABC) and at 26 years (Wechsler Adult Intelligence Scale, WAIS). Structural equation modeling (SEM) was used to model the effect of head growth on IQ. Results: On average, VP/VLBW had lower head circumference at birth (27.61 cm vs. 35.11 cm, mean difference 7.49, 95% confidence interval [7.09–7.90]) and lower adult intelligence scores (88.98 vs. 102.54, mean difference 13.56 [10.59–16.53]) than term born comparison individuals. Head circumference at birth (e.g., total effect β=.48; p<.001 for adult IQ) and head growth in childhood predicted intelligence development from age 6 to 26 years in both VP/VLBW and term born individuals (70% of variance in adult IQ explained by full model). Effects of gestation and birth weight on intelligence were fully mediated by head circumference and growth. Conclusions: This longitudinal investigation from birth to adulthood indicates head growth as a proxy of brain development and intelligence. Repeated early head circumference assessment adds valuable information when screening for long-term neurocognitive risk. (JINS, 2019, 25, 48#x2013;56)

Objectives: Although individuals with traumatic brain injury (TBI) often report higher levels of social isolation, little is known about the factors influencing their self-perception of loneliness. The aim of the current study was to investigate the relationship between loneliness, social network size, and personality variables (neuroticism and extraversion) after TBI, and in particular whether specific personality variables mediate the relationship between social network size and perception of loneliness. Methods: Here, we assessed self-reported loneliness, personality variables, and social network size of 24 individuals with moderate-to-severe TBI and 41 healthy comparison participants. We then carried out a mediation analysis to examine whether personality variables mediated the relationship between loneliness and social network size. Results: Our results indicate that individuals with TBI reported higher levels of loneliness and neuroticism, but there was no group difference in social network size or extraversion. The mediation analysis revealed that the association between social network size and loneliness was mediated by neuroticism, but not by extraversion. Conclusions: Our findings show that neuroticism is an intervening variable in the relationship between social network size and self-perception of loneliness in individuals with moderate-to-severe TBI, and presents a new possible target for clinicians and rehabilitators seeking to address reports of loneliness and social isolation in TBI. (JINS 2019, 25, 266–274)

Objective: Cognitive reserve (CR) capacity can be viewed as the maximum processing potential of neural systems that support adaptive cognitive performance in age-related cognitive decline. CR is a complex construct that can only be measured indirectly. Proxy measures (e.g., psychosocial/lifestyle variables) are traditionally used to reflect CR. However, strong relationships have been observed between these measures and cognitive functions (e.g., executive function [EF], processing resources [PR], fluid/crystallized abilities); therefore, the organizational structure of indicators implicated in CR remains unclear. The objective of this study was to test a hypothetical, theoretical model of CR capacity that includes both traditional CR proxy indicators and measures of cognitive function [Satz et al. (2011). Journal of Clinical and Experimental Neuropsychology, 33(1), 121–130], which remain, as yet, untested. Method: Construct validity of the model was investigated in healthy older adults through exploratory and confirmatory factor analysis (EFA and CFA) using data from the Maastricht Ageing Study (MAAS). A secondary CFA was conducted to validate the model using data from the Irish Longitudinal Study on Ageing (TILDA). Results: EFA and CFA in MAAS established a two-factor model comprising EF/PR and cumulative cognitive enrichment (CCE), which was further validated in a secondary analysis in TILDA. Convergent and discriminant validity was supported in MAAS (range of R2 = .228–.635; factor correlation confidence interval (CI) = .622, .740) and TILDA (range of R2 = .172–.899; factor correlation CI = .559, .624). Conclusions: A dual model of CR elucidated the relationships between hypothesized indicators of CR capacity and revealed a two-factor structure suggesting that both control (EF/PR) and representational processes (CCE) are involved in CR capacity.

Objectives: An important question in longitudinal research is whether the individuals who discontinue participation differ in their level of, or their change in, cognitive functioning relative to individuals who return for subsequent occasions. Methods: Performance in five cognitive domains was examined in nearly 5000 participants between 18 and 85 years of age who completed between one and five longitudinal occasions. Results: Little or no differences in cognitive performance were apparent between young adults who did or did not return for subsequent longitudinal occasions. However, among adults above about 45 years of age, returning participants had higher levels of cognitive performance, but approximately similar magnitude of longitudinal change, as participants completing fewer occasions. Conclusions: These results suggest that generalizability of longitudinal comparisons may be restricted to individuals with relatively high levels of cognitive functioning, but that rates of cognitive change are nearly comparable for individuals completing different numbers of longitudinal occasions.

Objective: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22–47 years following football retirement) using diffusion tensor imaging (DTI). Method: Forty former high school football players aged 40–65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. Results: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p < .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p < .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. Discussion: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.

Objective: Deficits in the semantic learning strategy were observed in subjects with amnestic mild cognitive impairment (aMCI) in our previous study. In the present study, we explored the contributions of executive function and brain structure changes to the decline in the semantic learning strategy in aMCI. Methods: A neuropsychological battery was used to test memory and executive function in 96 aMCI subjects and 90 age- and gender-matched healthy controls (HCs). The semantic clustering ratio on the verbal learning test was calculated to evaluate learning strategy. Medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) were measured on MRI with the MTA and Fazekas visual rating scales, respectively. Results: Compared to HCs, aMCI subjects had poorer performance in terms of memory, executive function, and the semantic clustering ratio (P < .001). In aMCI subjects, no significant correlation between learning strategy and executive function was observed. aMCI subjects with obvious MTA demonstrated a lower semantic clustering ratio than those without MTA (P < .001). There was no significant difference in the learning strategies between subjects with high-grade WMH and subjects with low-grade WMH. Conclusion: aMCI subjects showed obvious impairment in the semantic learning strategy, which was attributable to MTA but independent of executive dysfunction and subcortical WMH. These findings need to be further validated in large cohorts with biomarkers identified using volumetric brain measurements. (JINS, 2019, 25, 706–717)

Objective: Emotion recognition is an important aspect of emotion processing, which is needed for appropriate social behavior and normal socialization. Previous studies in adults with antisocial personality disorder or psychopathy, in those convicted of criminal behavior, or in children with conduct disorder show impairments in negative emotion recognition. The present study investigated affective facial and prosody recognition in a sample of children at high risk of developing future criminal behavior. Methods: Participants were 8- to 12-year-old children at high risk of developing criminal behavior (N=219, 83.1% boys) and typically developing controls (N=43, 72.1% boys). The high-risk children were recruited through an ongoing early intervention project of the city of Amsterdam, that focuses on the underage siblings or children of delinquents, and those failing to attend school. Facial and vocal recognition of happy, sad, angry, and fear was measured with the Facial Emotion Recognition (FER) test and the prosody test of the Amsterdam Neuropsychological Tasks (ANT), respectively. Results: The high-risk group was significantly worse in facial affect recognition and had particular problems with fear and sadness recognition. No hostile attribution bias was found. The high-risk group did not differ from controls in affective prosody recognition but needed significantly more time to recognize emotions. Conclusions: The emotion-specific deficits found in forensic and clinical populations are already present in a sample of children at high risk of developing future criminal behavior. These findings help us understand a possible underlying mechanism of antisocial behavior that could provide directions for tailored interventions. (JINS, 2019, 25, 57–64)

Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293–301)

Objectives: Antisaccade error rate has been proposed to be one of the most promising endophenotypes for schizophrenia. Increased error rate in patients has been associated with working memory, attention and other executive function impairments. The relationship between antisaccade error rate and other neuropsychological processes in patients compared to healthy controls has not been explored in depth. This study aimed to replicate the finding of heightened antisaccade error rate in patients and determine which cognitive processes were most strongly associated with antisaccade error rate in both patients and controls. In addition, the study investigated whether different antisaccade task paradigms engage different cognitive processes. Methods: One hundred and ninety-one participants (54 patients with schizophrenia/schizoaffective disorder and 137 controls) completed the antisaccade task, which included both gap and step task parameters. Neuropsychological measures were obtained using the MCCB and the Stroop task. Results: The current study replicated a pronounced antisaccade error rate deficit in patients. In patients, working memory variance was most significantly associated with antisaccade errors made during the step condition, while attentional processes were most associated with errors made during the gap condition. In controls, overall global cognitive performance was most associated with antisaccade rates for both gap and step conditions. Conclusions: The current study demonstrates that in schizophrenia patients, but not controls, elevated antisaccade error rate is associated with attention and working memory, but not with global cognitive impairment or psychopathological processes. Our novel findings demonstrate that the gap and step conditions of the antisaccade task engage different cognitive processes. (JINS, 2019, 25, 174–183)

Objectives: The current study used a mixed-method design to qualitatively examine parents’ definitions of resilience and factors they believed optimized their child’s early outcome following neonatal brain injury. This was followed by quantitative analyses of early developmental and mental health outcomes and their relation to salient biopsychosocial factors. Methods: Participants were parents of children diagnosed with neonatal brain injury due to stroke or hypoxic-ischemic encephalopathy (N=51; age range of children 18 months to 8 years). The Parent Experiences Questionnaire (PEQ) was used to qualitatively analyze parents’ open-ended responses about their child’s early experiences and outcome. The Child Behavior Checklist (CBCL) and Scales of Independent Behaviour Early Developmental Form (SIB-ED) parent ratings were used to measure child resilience from a quantitative perspective, identifying “at-risk” and “resilient” children using standard cutoffs. “Resilient” and “at-risk” children were compared on biopsychosocial variables using univariate t tests and chi-square analyses. Results: Parents provided five unique definitions of their child’s positive outcomes, and many children demonstrated resilience based on parent perspectives and quantitative definitions. Supporting factors included close medical follow-up, early intervention, and intrinsic factors within the child and parent. Group comparisons of “resilient” and “at-risk” children highlighted the importance of parent mental health across these early developmental and mental health outcomes. Conclusions: Many children were described as resilient during the early years by parents using qualitative and quantitative approaches. Findings highlighted the importance of parent well-being in promoting optimal early outcomes. (JINS, 2019, 25, 390–402.)