Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N=238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change. (JINS, 2015, 21, 573–583)

While neuropsychological deficits in both “hot” and “cool” executive functions (EFs) have been documented among individuals with attention-deficit/hyperactivity disorder (ADHD), these EF deficits are not universal across all individuals with this diagnosis. One potential moderator of executive dysfunction may be the presence of comorbid oppositional defiant disorder (ODD). This study examined the association between “hot” and “cool” EFs and comorbid ODD in children with ADHD. Thirty-three children with ADHD and comorbid ODD (ADHD+ODD), 67 with ADHD without ODD (ADHD-ODD), and 30 typically developing controls participated. Children were 7–12 years of age. “Cool” EFs were assessed with a spatial span task and a card sorting test. “Hot” EFs were assessed using a delay discounting task and a gambling task. ADHD-ODD and ADHD+ODD groups performed more poorly on “cool” EF tasks than controls, but did not differ from each other. Furthermore, the number of ADHD symptoms, but not ODD symptoms, was associated with “cool” EF scores. The three groups did not differ on “hot” EF tasks and the number of ADHD or ODD symptoms was unrelated to “hot” EF scores. In sum, children with ADHD presented with “cool” EF deficits which appear to be unrelated to ODD comorbidity. However, “hot” EF deficits were not present among children with ADHD, irrespective of comorbid ODD status. (JINS, 2015, 21, 584–595)

Neuropsychological assessment aims to identify individual performance profiles in multiple domains of cognitive functioning; however, substantial variation exists in how deficits are defined and what cutoffs are used, and there is no universally accepted definition of neuropsychological impairment. The aim of this study was to derive and validate a clinical case definition rule to identify neuropsychological impairment in children and adolescents. An existing normative pediatric sample was used to calculate base rates of abnormal functioning on eight measures covering six domains of neuropsychological functioning. The dataset was analyzed by varying the range of cutoff levels [1, 1.5, and 2 standard deviations (SDs) below the mean] and number of indicators of impairment. The derived rule was evaluated by bootstrap, internal and external clinical validation (orthopedic and traumatic brain injury). Our neuropsychological impairment (NPI) rule was defined as “two or more test scores that fall 1.5 SDs below the mean.” The rule identifies 5.1% of the total sample as impaired in the assessment battery and consistently targets between 3 and 7% of the population as impaired even when age, domains, and number of tests are varied. The NPI rate increases in groups known to exhibit cognitive deficits. The NPI rule provides a psychometrically derived method for interpreting performance across multiple tests and may be used in children 6–18 years. The rule may be useful to clinicians and scientists who wish to establish whether specific individuals or clinical populations present within expected norms versus impaired function across a battery of neuropsychological tests. (JINS, 2015, 21, 596–609)

Non-right handedness (NRH) is reportedly more common in very preterm (VPT; <32 weeks’ gestation) children compared with term-born peers, but it is unclear whether neonatal brain injury or altered brain morphology and microstructure underpins NRH in this population. Given that NRH has been inconsistently reported to be associated with cognitive and motor difficulties, this study aimed to examine associations between handedness and neurodevelopmental outcomes in VPT 7-year-olds. Furthermore, the relationship between neonatal brain injury and integrity of motor tracts (corpus callosum and corticospinal tract) with handedness at age 7 years in VPT children was explored. One hundred seventy-five VPT and 69 term-born children completed neuropsychological and motor assessments and a measure of handedness at 7 years’ corrected age. At term-equivalent age, brain injury on MRI was assessed and diffusion tensor measures were obtained for the corpus callosum and posterior limb of the internal capsule. There was little evidence of stronger NRH in the VPT group compared with term controls (regression coefficient [b] −1.95, 95% confidence interval [−5.67, 1.77]). Poorer academic and working memory outcomes were associated with stronger NRH in the VPT group. While there was little evidence that neonatal unilateral brain injury was associated with stronger NRH, increased area and fractional anisotropy of the corpus callosum splenium were predictive of stronger NRH in the VPT group. VPT birth may alter the relationship between handedness and academic outcomes, and neonatal corpus callosum integrity predicts hand preference in VPT children at school age. (JINS, 2015, 21, 610–621)

This study investigated the relationship between insulin-resistance and constituent components of executive function in a sample of neurologically intact older adult subjects using the homeostasis model assessment (HOMA-IR) and latent factors of working memory, cognitive control and processing speed derived from confirmatory factor analysis. Low-density lipoprotein (LDL), mean arterial pressure (MAP), along with body mass index (BMI) and white matter hypointensity (WMH) were used to control for vascular risk factors, adiposity and cerebrovascular injury. The study included 119 elderly subjects recruited from the University of California, San Francisco Memory and Aging Center. Subjects underwent neuropsychological assessment, fasting blood draw and brain magnetic resonance imaging (MRI). Partial correlations and linear regression models were used to examine the HOMA-IR-executive function relationship. Pearson correlation adjusting for age showed a significant relationship between HOMA-IR and working memory (rp=−.18; p=.047), a trend with cognitive control (rp=−.17; p=.068), and no relationship with processing speed (rp=.013; p=.892). Linear regression models adjusting for demographic factors (age, education, and gender), LDL, MAP, BMI, and WMH indicated that HOMA-IR was negatively associated with cognitive control (r=−.256; p=.026) and working memory (r=−.234; p=.054). These results suggest a greater level of peripheral insulin-resistance is associated with decreased cognitive control and working memory. After controlling for demographic factors, vascular risk, adiposity and cerebrovascular injury, HOMA-IR remained significantly associated with cognitive control, with working memory showing a trend. These findings substantiate the insulin-resistance-executive function hypothesis and suggest a complex interaction, demonstrated by the differential impact of insulin-resistance on processing speed and specific aspects of executive function. (JINS, 2015, 21, 622–628)

Aberrant semantic processing has been linked to the etiology of formal thought disorder (TD) symptoms in schizophrenia. In this cross-sectional study, two prominent theories, overactivation and disorganized structure of semantic memory (SM), were examined in relation to TD symptoms using the continuum approach across two established semantic tasks (direct/indirect semantic priming and categorical fluency). The aim was to examine the validity of the two TD theories in relation to TD symptoms in schizophrenia. Greater direct and indirect priming, fluency productivity and category errors were expected if the data supported the overactivation theory. Reduced fluency productivity and increased category errors would be characteristic of disorganized storage. Fifty-seven schizophrenia/schizoaffective disorder patients and 48 controls completed a clinical assessment and the semantic tasks. There was significantly reduced direct priming in patients compared to controls (p<.05), while indirect priming was not significantly different; there was no association between TD and degree of priming. Patients produced more category-inappropriate words (p<.005) than controls, which was related to increasing severity of circumstantiality. The pattern of results was more indicative of a disorganized SM storage problem in this sample. This phenomenon may underlie some TD symptoms in general schizophrenia. The findings strengthen the relationship between SM deficits and TD symptoms, though this appears to differ between individual symptoms. The authors discuss the value of the continuum approach in addressing research questions in TD etiology. Given low levels of TD in this study, replication of these findings in a sample with greater TD is desirable. (JINS, 2015, 21, 629–638)

Both errorless learning (EL) and Goal Management Training (GMT) have been shown effective cognitive rehabilitation methods aimed at optimizing the performance on everyday skills after brain injury. We examine whether a combination of EL and GMT is superior to traditional GMT for training complex daily tasks in brain-injured patients with executive dysfunction. This was an assessor-blinded randomized controlled trial conducted in 67 patients with executive impairments due to brain injury of non-progressive nature (minimal post-onset time: 3 months), referred for outpatient rehabilitation. Individually selected everyday tasks were trained using 8 sessions of an experimental combination of EL and GMT or via conventional GMT, which follows a trial-and-error approach. Primary outcome measure was everyday task performance assessed after treatment compared to baseline. Goal attainment scaling, rated by both trainers and patients, was used as secondary outcome measure. EL-GMT improved everyday task performance significantly more than conventional GMT (adjusted difference 15.43, 95% confidence interval [CI] [4.52, 26.35]; Cohen’s d=0.74). Goal attainment, as scored by the trainers, was significantly higher after EL-GMT compared to conventional GMT (mean difference 7.34, 95% CI [2.99, 11.68]; Cohen’s d=0.87). The patients’ goal attainment scores did not differ between the two treatment arms (mean difference 3.51, 95% CI [−1.41, 8.44]). Our study is the first to show that preventing the occurrence of errors during executive strategy training enhances the acquisition of everyday activities. A combined EL-GMT intervention is a valuable contribution to cognitive rehabilitation in clinical practice. (JINS, 2015, 21, 639–649)

Traumatic brain injury (TBI) is associated with long-term changes in daily life functioning, yet the neuroanatomical correlates of these changes are poorly understood. This study related outcome assessed across several domains to brain structure derived from quantitative magnetic resonance imaging (MRI). Sixty individuals spanning a wide range of TBI severity participated 1-year post-injury as part of the Toronto TBI study. Volumetric data over 38 brain regions were derived from high resolution T1-weighted MRI scans. Functioning was assessed with a battery of self- and significant-other rated measures. Multivariate analysis (partial least squares) was used to identify shared variance between the neuroimaging and outcome measures. TBI was associated with item endorsement on outcome questionnaires without strong evidence for severity or focal lesion effects. Prefrontal midline, cingulate, medial temporal, right inferior parietal and basal ganglia/thalamic volumes were associated with measures of initiative, energization, and physical complaints. In the chronic stage of TBI, self-initiation, energization, and physical complaints related to a specific pattern of volume loss in midline and lateral regions known to be involved in motivation, apathy, and attention. These results suggest that crucial functional changes in chronic TBI may be associated with volume loss in established midline-frontal and attentional circuits. (JINS, 2015, 21, 650–655)