The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise. (JINS, 2015, 21, 791–801)

The knowledge about personality traits in Parkinson’s disease (PD) is still limited. In particular, disgust proneness has not been investigated as well as its neuronal correlates. Although several morphometric studies demonstrated that PD is associated with gray matter volume (GMV) reduction in olfactory and gustatory regions involved in disgust processing, a possible correlation with disgust proneness has not been investigated. We conducted a voxel-based morphometry analysis to compare GMV between 16 cognitively normal male PD patients with mild to moderate symptoms and 24 matched control subjects. All participants had answered questionnaires for the assessment of disgust proneness, trait anger and trait anxiety. We correlated questionnaire scores with GMV in both groups. The clinical group reported selectively reduced disgust proneness toward olfactory stimuli associated with spoilage. Moreover, they showed GMV reduction in the central olfactory system [orbitofrontal cortex (OFC) and piriform cortex]. Disgust items referring to olfactory processing were positively correlated with OFC volume in PD patients. Our data suggest an association between PD-associated neurodegeneration and olfactory related facets of the personality trait disgust proneness. (JINS, 2015, 21, 314–317)

Our objective was to determine whether a Symbol Search paradigm developed for functional magnetic resonance imaging (FMRI) is a reliable and valid measure of cognitive processing speed (CPS) in healthy older adults. As all older adults are expected to experience cognitive declines due to aging, and CPS is one of the domains most affected by age, establishing a reliable and valid measure of CPS that can be administered inside an MR scanner may prove invaluable in future clinical and research settings. We evaluated the reliability and construct validity of a newly developed FMRI Symbol Search task by comparing participants’ performance in and outside of the scanner and to the widely used and standardized Symbol Search subtest of the Wechsler Adult Intelligence Scale (WAIS). A brief battery of neuropsychological measures was also administered to assess the convergent and discriminant validity of the FMRI Symbol Search task. The FMRI Symbol Search task demonstrated high test–retest reliability when compared to performance on the same task administered out of the scanner (r=.791; p<.001). The criterion validity of the new task was supported, as it exhibited a strong positive correlation with the WAIS Symbol Search (r=.717; p<.001). Predicted convergent and discriminant validity patterns of the FMRI Symbol Search task were also observed. The FMRI Symbol Search task is a reliable and valid measure of CPS in healthy older adults and exhibits expected sensitivity to the effects of age on CPS performance. (JINS, 2015, 22, 1–8)

A symptom of mild cognitive impairment (MCI) and Alzheimer’s disease(AD) is a flat learning profile. Learning slope calculation methods vary, andthe optimal method for capturing neuroanatomical changes associated with MCI andearly AD pathology is unclear. This study cross-sectionally compared fourdifferent learning slope measures from the Rey Auditory Verbal Learning Test(simple slope, regression-based slope, two-slope method, peak slope) tostructural neuroimaging markers of early AD neurodegeneration (hippocampalvolume, cortical thickness in parahippocampal gyrus, precuneus, and lateralprefrontal cortex) across the cognitive aging spectrum [normalcontrol (NC); (n=198;age=76±5), MCI (n=370;age=75±7), and AD (n=171;age=76±7)] in ADNI. Within diagnostic group,general linear models related slope methods individually to neuroimagingvariables, adjusting for age, sex, education, and APOE4 status. Among MCI,better learning performance on simple slope, regression-based slope, and lateslope (Trial 2–5) from the two-slope method related to largerparahippocampal thickness (all p-values<.01) andhippocampal volume (p<.01). Better regression-basedslope (p<.01) and late slope(p<.01) were related to larger ventrolateralprefrontal cortex in MCI. No significant associations emerged between any slopeand neuroimaging variables for NC (p-values ≥.05) orAD (p-values ≥.02). Better learning performancesrelated to larger medial temporal lobe (i.e., hippocampal volume,parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCIonly. Regression-based and late slope were most highly correlated withneuroimaging markers and explained more variance above and beyond other commonmemory indices, such as total learning. Simple slope may offer an acceptablealternative given its ease of calculation. (JINS, 2015,21, 455–467)

Based on previous studies demonstrating detrimental effects of reduced alertness on attentional orienting our study seeks to examine covert and overt attentional orienting in different arousal states. We hypothesized an attentional asymmetry with increasing reaction times to stimuli presented to the left visual field in a state of maximally reduced arousal. Eleven healthy participants underwent sleep deprivation and were examined repeatedly every 4 hr over 28 hr in total with two tasks measuring covert and overt orienting of attention. Contrary to our hypothesis, a reduction of arousal did not induce any asymmetry of overt orienting. Even in participants with profound and significant attentional asymmetries in covert orienting no substantial reaction time differences between left- and right-sided targets in the overt orienting task could be observed. This result is not in agreement with assumptions of a tight coupling of covert and overt attentional processes. In conclusion, we found differential effects of lowered arousal induced by sleep deprivation on covert and overt orienting of attention. This pattern of results points to a neuronal non-overlap of brain structures subserving these functions and a differential influence of the norepinephrine system on these modes of spatial attention. (JINS, 2015, 21, 545–557)

The aim of this study was to examine whether people differed in change in performance across the first five blocks of an online flanker task and whether those trajectories of change were associated with self-reported aerobic or resistance exercise frequency according to age. A total of 8752 men and women aged 13–89 completed a lifestyle survey and five 45-s games (each game was a block of ~46 trials) of an online flanker task. Accuracy of the congruent and incongruent flanker stimuli was analyzed using latent class and growth curve modeling adjusting for time between blocks, whether the blocks occurred on the same or different days, education, smoking, sleep, caffeinated coffee and tea use, and Lumosity training status (“free play” or part of a “daily brain workout”). Aerobic and resistance exercise were unrelated to first block accuracies. For the more cognitively demanding incongruent flanker stimuli, aerobic activity was positively related to the linear increase in accuracy [B=0.577%, 95% confidence interval (CI), 0.112 to 1.25 per day above the weekly mean of 2.8 days] and inversely related to the quadratic deceleration of accuracy gains (B=−0.619% CI, −1.117 to −0.121 per day). An interaction of aerobic activity with age indicated that active participants younger than age 45 had a larger linear increase and a smaller quadratic deceleration compared to other participants. Age moderates the association between self-reported aerobic, but not self-reported resistance, exercise and changes in cognitive control that occur with practice during incongruent presentations across five blocks of a 45-s online, flanker task. (JINS, 2015, 21, 802–815)

Demographic factors impact neuropsychological test performances and accounting for them may help to better elucidate current brain functioning. The NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neuropsychological tool, yet the original norms developed for the battery did not adequately account for important demographic/cultural factors known to impact test performances. We developed norms fully adjusting for all demographic variables within each language group (English and Spanish) separately. The current study describes the standards for individuals tested in English. Neurologically healthy adults (n=1038) and children (n=2917) who completed the NIH Toolbox norming project in English were included. We created uncorrected scores weighted to the 2010 Census demographics, and applied polynomial regression models to develop age-corrected and fully demographically adjusted (age, education, sex, race/ethnicity) scores for each NIHTB-CB test and composite (i.e., Fluid, Crystallized, and Total Composites). On uncorrected NIHTB-CB scores, age and education demonstrated significant, medium-to-large associations, while sex showed smaller, but statistically significant effects. In terms of race/ethnicity, a significant stair-step effect on uncorrected NIHTB-CB scores was observed (African American<Hispanic<White). After applying normative corrections, NIHTB-CB no longer demonstrated any significant associations with demographic factors. The previously developed norms still maintained significant associations with demographic factors, and demonstrated more variable impairment rates in segments of the healthy normative sample. Similar to other neuropsychological tests, demographic factors demonstrated significant associations with unadjusted NIHTB-CB scores. Application of fully corrected scores will help account for unwanted variance that is associated with non-clinical factors to more accurately reflect effects of disease-related changes in brain function. (JINS, 2015, 21, 378–391)

The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with frontostriatal dysfunction. While frontostriatal systems play a key role in behavioral inhibition, there are to our knowledge no fMRI studies investigating the potential impact of HIV on systems involved during the inhibition of voluntary movement. A total of 17 combined antiretroviral therapy (cART) naïve HIV+ participants as well as 18 age, gender, ethnic, education matched healthy controls performed a modified version of the stop-signal paradigm. This paradigm assessed behavior as well as functional brain activity associated with motor execution, reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing before stopping). HIV+ participants showed significantly slower responses during motor execution compared to healthy controls, whereas they had normal proactive response slowing. Putamen hypoactivation was evident in the HIV+ participants based on successful stopping, indicating subcortical dysfunction during reactive inhibition. HIV+ participants showed normal cortical functioning during proactive inhibition. Our data provide evidence that HIV infection is associated with subcortical dysfunction during reactive inhibition, accompanied by relatively normal higher cortical functioning during proactive inhibition. This suggests that HIV infection may primarily involve basic striatal-mediated control processes in cART naïve participants. (JINS, 2015, 21, 722–731)

Naming or word-finding tasks are a mainstay of the typical neuropsychological evaluation, particularly with older adults. However, many older adults have significant visual impairment and there are currently no such word-finding tasks developed for use with older visually impaired populations. This study presents a verbal, non-visual measure of word-finding for use in the evaluation of older adults with possible dysnomia. Stimuli were chosen based on their frequency of usage in everyday spoken language. A 60-item scale was created and given to 131 older Veterans. Rasch analyses were conducted and differential item functioning assessed to eliminate poorly-performing items. The final 55-item scale had a coefficient alpha of 0.84 and correlated with the Neuropsychological Assessment Battery Naming test, r=0.84, p<.01, Delis-Kaplan Executive Function System (D-KEFS) Category Fluency, r=0.45, p<.01, and the D-KEFS Letter Fluency, r=0.40, p<.01. ROC analyses found the measure to have sensitivity of 79% and specificity of 85% for detecting dysnomia. Patients with dysnomia performed worse on the measure than patients with intact word-finding, t(84)=8.2, p<.001. Patients with no cognitive impairment performed significantly better than patients with mild cognitive impairment, who performed significantly better than patients with dementia. This new measure shows promise in the neuropsychological evaluation of word-finding ability in older adults with or without visual impairment. Future directions include the development of a shorter version and the generation of additional normative data. (JINS, 2015, 21, 1–10)

Children with fetal alcohol spectrum disorders (FASD) show sociobehavioral impairments; however, the social cognitive profile contributing to these impairments is poorly understood. This study compared social perspective taking and empathy in children with FASD versus typically developing controls (TDC). Thirty-seven children with FASD and 21 TDC participated. Measures included parent-rated CBCL and SSIS, and NEPSY-II Theory of Mind, Test of Social Cognition and Index of Empathy. Parents rated the FASD group higher than TDC on indices of behavior problems and lower on indices of social skills and empathy. Children with FASD scored significantly below TDC on tasks requiring complex social cognition. The majority of correlations between social cognition and parent-ratings were not significant in FASD and TDC, with the exception of a negative correlation between self-reported empathy and parent-rated behavior difficulties in TDC. FASD subgroup analyses revealed lower theory of mind and empathy scores among children with ARND than pFAS/FAS. With regard to sex, males with FASD were rated as having more behavior difficulties than females, whereas TDC females obtained higher empathy ratings than males. In both groups, females scored higher on theory of mind and empathy indices. On theory of mind tasks, older children with FASD performed below younger, whereas younger TDC children performed more poorly than older. Children with FASD show reduced functioning on indices of sociobehavioral and social cognition, and the effects are influenced by sex and age. These findings provide insight into the clinical and social profile of children with FASD. (JINS, 2015, 21, 74–84)

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)

Perceived cognitive difficulties and cognitive impairment are important determinants of employment in people with multiple sclerosis (pwMS). However, it is not clear how they are related to adverse work outcomes and whether the relationship is influenced by depressive symptoms. Thus, this study examined perceived and actual general cognitive and prospective memory function, and cognitive appraisal accuracy, in relation to adverse work outcomes. The possible mediating and/or moderating role of depression was also examined. A cross-sectional community-based sample of 111 participants (33 males, 78 females) completed the Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ), Beck Depression Inventory – Fast Screen (BDI-FS), and questions related to their current or past employment. They then underwent cognitive testing using the Screening Examination for Cognitive Impairment, Auditory Consonant Trigrams test, Zoo Map Test, and Cambridge Prospective Memory Test. Perceived general cognitive and prospective memory difficulties in the workplace and performance on the respective cognitive tests were found to predict unemployment and reduced work hours since MS diagnosis due to MS. Depression was also related to reduced work hours, but it did not explain the relationship between perceived cognitive difficulties and the work outcomes. Nor was it related to cognitive test performance. The results highlight a need to address the perceptions of cognitive difficulties together with cognitive impairment and levels of depression in vocational rehabilitation programs in pwMS. (JINS, 2015, 21, 156–168)

The relationship between subjective memory complaints (SM) and objective memory (OM) performance in aging has been variably characterized in a substantial literature, to date. In particular, cross-sectional studies often observe weak or no associations. We investigated whether subjective memory complaints and objectively measured cognition influence each other over time, and if so, which is the stronger pathway of change—objective to subjective, or subjective to objective—or whether they are both important. Using bivariate latent change score modeling in data from a population study (N=1980) over 5 annual assessment cycles, we tested four corresponding hypotheses: (1) no coupling between SM and OM over time; (2) SM as leading indicator of change in OM; (3) OM as leading indicator of change in SM; (4) dual coupling over time, with both SM and OM leading subsequent change in the other. We also extended objective cognition to two other domains, language and executive functions. The dual-coupling models best fit the data for all three objective cognitive domains. The SM–OM temporal dynamics differ qualitatively compared to other domains, potentially reflecting changes in insight and self-awareness specific to memory impairment. Subjective memory and objective cognition reciprocally influence each other over time. The temporal dynamics between subjective and objective cognition in aging are nuanced, and must be carefully disentangled to shed light on the underlying processes. (JINS, 2015, 21, 732–742)

The base rates of abnormal test scores in cognitively normal samples have been a focus of recent research. The goal of the current study is to illustrate how Bayes’ theorem uses these base rates—along with the same base rates in cognitively impaired samples and prevalence rates of cognitive impairment—to yield probability values that are more useful for making judgments about the absence or presence of cognitive impairment. Correlation matrices, means, and standard deviations were obtained from the Wechsler Memory Scale –4th Edition (WMS-IV) Technical and Interpretive Manual and used in Monte Carlo simulations to estimate the base rates of abnormal test scores in the standardization and special groups (mixed clinical) samples. Bayes’ theorem was applied to these estimates to identify probabilities of normal cognition based on the number of abnormal test scores observed. Abnormal scores were common in the standardization sample (65.4% scoring below a scaled score of 7 on at least one subtest) and more common in the mixed clinical sample (85.6% scoring below a scaled score of 7 on at least one subtest). Probabilities varied according to the number of abnormal test scores, base rates of normal cognition, and cutoff scores. The results suggest that interpretation of base rates obtained from cognitively healthy samples must also account for data from cognitively impaired samples. Bayes’ theorem can help neuropsychologists answer questions about the probability that an individual examinee is cognitively healthy based on the number of abnormal test scores observed. (JINS, 2015, 21, 1–9)

Previous studies suggest that executive functions influence the performance on visuoconstructional tasks. This study aims to investigate whether the relationship between planning ability and the copy of complex figures is mediated by distinct components of executive functions (i.e., working memory, inhibitory control and cognitive flexibility). We included a 129 older adults with Alzheimer’s disease (n=36, AD), mild cognitive impairment (MCI, n=67), and with no evidence of cognitive impairment (controls, n=26). We evaluated the mediation effect of planning abilities, working memory, cognitive flexibility and inhibitory control on visuoconstructional tasks using a multiple mediation models. We found a significant direct effect of planning on visuoconstructional abilities and a partial mediation effect of working memory and cognitive flexibility on visuoconstructional abilities. The present results indicate that the performance on visuoconstructional task is mediated by multiple interrelated executive functions components, in particular working memory and cognitive flexibility. (JINS, 2015, 21, 392–398)

Given the substantial overlap in cognitive dysfunction between bipolar disorder (BD) and schizophrenia (SZ), we examined the utility of the MATRICS Consensus Cognitive Battery (MCCB)—developed for use in SZ—for the measurement of cognition in patients with BD with psychosis (BDP) and its association with community functioning. The MCCB, Multnomah Community Ability Scale, and measures of clinical symptoms were administered to participants with BDP (n=56), SZ (n=37), and healthy controls (HC) (n=57). Groups were compared on clinical and cognitive measures; linear regressions examined associations between MCCB and community functioning. BDP and SZ groups performed significantly worse than HC on most neurocognitive domains; BDP and HC did not differ on Social Cognition. Patients with BDP performed better than patients with SZ on most cognitive measures, although groups only differed on social cognition, working memory, verbal memory, and the composite after controlling for clinical variables. MCCB was not associated with community functioning. The MCCB is an appropriate measure of neurocognition in BDP but does not appear to capture social cognitive deficits in this population. The addition of appropriate social cognitive measures is recommended. (JINS, 2015, 21, 468–472)

Longitudinal normative data obtained from a robust elderly sample (i.e., believed to be free from neurodegenerative disease) are sparse. The purpose of the present study was to develop reliable change indices (RCIs) that can assist with interpretation of test score changes relative to a healthy sample of older adults (ages 50+). Participants were 4217 individuals who completed at least three annual evaluations at one of 34 past and present Alzheimer’s Disease Centers throughout the United States. All participants were diagnosed as cognitively normal at every study visit, which ranged from three to nine approximately annual evaluations. One-year RCIs were calculated for 11 neuropsychological variables in the Uniform Data Set by regressing follow-up test scores onto baseline test scores, age, education, visit number, post-baseline assessment interval, race, and sex in a linear mixed effects regression framework. In addition, the cumulative frequency distributions of raw score changes were examined to describe the base rates of test score changes. Baseline test score, age, education, and race were robust predictors of follow-up test scores across most tests. The effects of maturation (aging) were more pronounced on tests related to attention and executive functioning, whereas practice effects were more pronounced on tests of episodic and semantic memory. Interpretation of longitudinal changes on 11 cognitive test variables can be facilitated through the use of reliable change intervals and base rates of score changes in this robust sample of older adults. A Web-based calculator is provided to assist neuropsychologists with interpretation of longitudinal change. (JINS, 2015, 21, 558–567)

To determine if total lifetime physical activity (PA) is associated with better cognitive functioning with aging and if cerebrovascular function mediates this association. A sample of 226 (52.2% female) community dwelling middle-aged and older adults (66.5±6.4 years) in the Brain in Motion Study, completed the Lifetime Total Physical Activity Questionnaire and underwent neuropsychological and cerebrovascular blood flow testing. Multiple robust linear regressions were used to model the associations between lifetime PA and global cognition after adjusting for age, sex, North American Adult Reading Test results (i.e., an estimate of premorbid intellectual ability), maximal aerobic capacity, body mass index and interactions between age, sex, and lifetime PA. Mediation analysis assessed the effect of cerebrovascular measures on the association between lifetime PA and global cognition. Post hoc analyses assessed past year PA and current fitness levels relation to global cognition and cerebrovascular measures. Better global cognitive performance was associated with higher lifetime PA (p=.045), recreational PA (p=.021), and vigorous intensity PA (p=.004), PA between the ages of 0 and 20 years (p=.036), and between the ages of 21 and 35 years (p<.0001). Cerebrovascular measures did not mediate the association between PA and global cognition scores (p>.5), but partially mediated the relation between current fitness and global cognition. This study revealed significant associations between higher levels of PA (i.e., total lifetime, recreational, vigorous PA, and past year) and better cognitive function in later life. Current fitness levels relation to cognitive function may be partially mediated through current cerebrovascular function. (JINS, 2015, 21, 816–830)

Part B of the Trail Making Test (TMT-B) is one of the most widely used neuropsychological tests of “executive” function. A commonly held assumption is that the TMT-B can be used to detect frontal executive dysfunction. However, so far, research evidence has been limited and somewhat inconclusive. In this retrospective study, performance on the TMT-B of 55 patients with known focal frontal lesions, 27 patients with focal non-frontal lesions and 70 healthy controls was compared. Completion time and the number of errors made were examined. Patients with frontal and non-frontal lesions performed significantly worse than healthy controls for both completion time and the number of errors. However, there was no significant difference for both completion time and the number of errors when patients with frontal and non-frontal lesions were compared. Performance was also not significantly different between patients with focal lesions within different regions of the frontal lobe (orbital, left lateral, right lateral, medial). Our findings suggest that the TMT-B is a robust test for detection of brain dysfunction. However, its capacity for detecting frontal executive dysfunction appears rather limited. Clinicians should be cautious when drawing conclusions from performance on the TMT-B alone. (JINS, 2015, 21, 169–174)