Environmental dependency (ED) phenomena, including utilization behavior and imitation behavior, are clinical manifestations typically observed in patients with the behavioral variant of fronto-temporal dementia (bvFTD), who may also show the closing-in (CI) phenomenon. Here, we explored the neuropsychological correlates of ED and CI in bvFTD, and the association of ED with CI to clarify the mechanisms underlying these clinical manifestations. Thirty-one bvFTD patients underwent a wide cognitive assessment in addition to special tasks to detect occurrence of CI and ED phenomena. Both ED and CI phenomena were present in more than half of the sample. Logistic regression analyses revealed that both ED and CI phenomena were significantly associated with poor scores on frontal neuropsychological tests. Although ED and CI often co-occurred, 3/12 patients with CI did not show ED, and 5/18 patients with ED did not show CI. A logistic regression model showed that the presence of ED was not significantly associated to CI. CI and ED are associated to progressive derangement of frontal functions in bvFTD. However, specific frontal dysfunctions might explain the occurrence of either phenomenon in isolation. (JINS, 2015, 21, 1–7)

Although cognitive deficits are common in patients with chronic heart failure (CHF), no study to date has investigated whether these deficits extend to the capacity to execute delayed intentions (prospective memory, PM). This is a surprising omission given the critical role PM plays in correctly implementing many important CHF self-care behaviors. The present study aimed to provide the first empirical assessment of PM function in people with CHF. The key dependent measure was a laboratory measure of PM that closely simulates PM tasks in daily life – Virtual Week. A group comparison design was used, with 30 CHF patients compared to 30 demographically matched controls. Background measures assessing executive functions, working memory, and verbal memory were also administered. The CHF group exhibited significant PM impairment, with difficulties generalizing across different types of PM tasks (event, time, regular, irregular). The CHF group also had moderate deficits on several of the background cognitive measures. Given the level of impairment remained consistent even on tasks that imposed minimal demands on memory for task content, CHF-related difficulties most likely reflects problems with the prospective component. However, exploratory analyses suggest that difficulties with retrospective memory and global cognition (but not executive control), also contribute to the PM difficulties seen in this group. The implications of these data are discussed, and in particular, it is argued that problems with PM may help explain why patient engagement in CHF self-care behaviors is often poor. (JINS, 2015, 21, 1–10)

Education and related proxies for cognitive reserve (CR) are confounded by associations with environmental factors that correlate with cerebrovascular disease possibly explaining discrepancies between studies examining their relationships to cognitive aging and dementia. In contrast, sex-related memory differences may be a better proxy. Since they arise developmentally, they are less likely to reflect environmental confounds. Women outperform men on verbal and men generally outperform women on visuospatial memory tasks. Furthermore, memory declines during the preclinical stage of AD, when it is clinically indistinguishable from normal aging. To determine whether CR mitigates age-related memory decline, we examined the effects of gender and APOE genotype on longitudinal memory performances. Memory decline was assessed in a cohort of healthy men and women enriched for APOE ɛ4 who completed two verbal [Rey Auditory Verbal Learning Test (AVLT), Buschke Selective Reminding Test (SRT)] and two visuospatial [Rey-Osterrieth Complex Figure Test (CFT), and Benton Visual Retention Test (VRT)] memory tests, as well as in a separate larger and older cohort [National Alzheimer’s Coordinating Center (NACC)] who completed a verbal memory test (Logical Memory). Age-related memory decline was accelerated in APOE ɛ4 carriers on all verbal memory measures (AVLT, p=.03; SRT p<.001; logical memory p<.001) and on the VRT p=.006. Baseline sex associated differences were retained over time, but no sex differences in rate of decline were found for any measure in either cohort. Sex-based memory advantage does not mitigate age-related memory decline in either APOE ɛ4 carriers or non-carriers. (JINS, 2015, 21, 95–104)

Parkinson’s disease (PD) is characterized by asymmetric motor symptom onset attributed to greater degeneration of dopamine neurons contralateral to the affected side. However, whether motor asymmetries predict cognitive profiles in PD, and to what extent dopamine influences cognition remains controversial. This study evaluated cognitive variability in PD by measuring differential response to dopamine replacement therapy (DRT) based on hemispheric asymmetries. The influence of DRT on cognition was evaluated in mild PD patients (n=36) with left or right motor onset symptoms. All subjects were evaluated on neuropsychological measures on and off DRT and compared to controls (n=42). PD patients were impaired in executive, memory and motor domains irrespective of side of motor onset, although patients with left hemisphere deficit displayed greater cognitive impairment. Patients with right hemisphere deficit responded to DRT with significant improvement in sensorimotor deficits, and with corresponding improvement in attention and verbal memory functions. Conversely, patients with greater left hemisphere dopamine deficiency did not improve in attentional functions and declined in verbal memory recall following DRT. These findings support the presence of extensive mild cognitive deficits in early PD not fully explained by dopamine depletion alone. The paradoxical effects of levodopa on verbal memory were predicted by extent of fine motor impairment and sensorimotor response to levodopa, which reflects extent of dopamine depletion. The findings are discussed with respect to factors influencing variable cognitive profiles in early PD, including hemispheric asymmetries and differential response to levodopa based on dopamine levels predicting amelioration or overdosing. (JINS, 2015, 21, 259–270)

Impaired self-awareness after traumatic brain injury (TBI) is often seen in stark contrast to the observations of significant-others, who are acutely aware of the difficulties experienced by patients. Our objective was to investigate the relationship between metacognitive knowledge in daily life and emergent awareness of errors during laboratory tasks, since the breakdown of error detection mechanisms may impose limitations on the recovery of metacognitive knowledge after TBI. We also examined the extent to which these measures of awareness can predict dysexecutive behaviors. A sample of TBI patients (n=62) and their significant-others, provided reports of daily functioning post injury. In addition, patients underwent a neuropsychological assessment and were instructed to signal their errors during go/no-go tests. Interrelationships between metacognitive and emergent levels of awareness were examined, after controlling for the influence of secondary cognitive variables. Significant-other ratings correlated with errors made by the patients on neuropsychological tests but not with their premorbid function. Patients who under-reported daily life difficulties or over-reported their competency, compared to significant-other reports, were less likely to show awareness of laboratory errors. Emergent awareness was also identified as the sole predictor of performance on the modified six-element test, an ecologically valid test of multitasking. The online breakdown of error awareness after brain injury is related to difficulties with metacognitive awareness as reported in daily life, and is also predictive of dysexecutive behaviors. These findings are discussed in the context of multidimensional and neural models of awareness and error monitoring. (JINS, 2015, 21, 473–482)

The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are now aging into adulthood, and concerns are growing about the development of radiotherapy-induced cognitive deficits in the aging brain. These deficits are hypothesized to increase over time. Their impact on daily functioning of older survivors, and the accompanying need for interventions, should be anticipated. By describing a detailed profile of executive function deficits and their associations with age, specific targets for neuropsychological intervention can be identified. Fifty survivors of childhood lymphoid malignancies and 58 related controls were assessed with the Amsterdam Neuropsychological Tasks program. The survivors were on average 31.1 (4.9) years old, treated with 22.5 (6.8) Gy cranial irradiation, and examined on average 25.5 (3.1) years after diagnosis. The survivors showed significantly decreased response speed, irrespective of the task at hand. Furthermore, we found deficits in working memory capacity, inhibition, cognitive flexibility, executive visuomotor control, attentional fluctuations, and sustained attention. Older age was associated with poorer performance on executive visuomotor control and inhibition. On executive visuomotor control, 50% of female survivors performed more than 1.5 SD below average, versus 15.4% of male survivors. The combination of visuospatial working memory problems and decreasing executive visuomotor control could result in difficulty with learning new motor skills at older ages, like walking with a cane. Deterioration of executive control and inhibition may result in decreased behavioral and emotional regulation in aging survivors. Especially the deficiency in executive visuomotor control in female survivors should be considered for (prophylactic) intervention. (JINS, 2015, 21, 657–669)

Human neuroimaging studies of reward processing typically involve tasks that engage decision-making processes in the dorsal striatum or focus upon the ventral striatum’s response to feedback expectancy. These studies are often compared to the animal literature; however, some animal studies include both feedback and nonfeedback events that activate the dorsal striatum during feedback expectancy. Differences in task parameters, movement complexity, and motoric effort to attain rewards may partly explain ventral and dorsal striatal response differences across species. We, therefore, used a target capture task during functional neuroimaging that was inspired by a study of single cell modulation in the internal globus pallidus during reward-cued, rotational arm movements in nonhuman primates. In this functional magnetic resonance imaging study, participants used a fiberoptic joystick to make a rotational response to an instruction stimulus that indicated both a target location for a capture movement and whether or not the trial would end with feedback indicating either a small financial gain or a neutral outcome. Portions of the dorsal striatum and pallidum demonstrated greater neural activation to visual cues predicting potential gains relative to cues with no associated outcome. Furthermore, both striatal and pallidal regions displayed a greater response to financial gains relative to neutral outcomes. This reward-dependent modulation of dorsal striatal and pallidal activation in a target-capture task is consistent with findings from reward studies in animals, supporting the use of motorically complex tasks as translational paradigms to investigate the neural substrates of reward expectancy and outcome in humans. (JINS, 2015, 21, 399–411)

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)

Cognitive functioning, particularly executive functioning, is a strong predictor of functional outcomes in people with schizophrenia. Cognitive remediation has been shown to improve specific cognitive processes, but adjunctive interventions are required for meaningful gains in adaptive functioning, particularly in people with chronic illness. This study examined whether (and how) environmental adaptations, used without training, may circumvent cognitive difficulties and facilitate everyday task performance in individuals with chronic schizophrenia. Forty-two individuals with chronic schizophrenia/schizoaffective disorder were administered cognitive measures and two versions of the Naturalistic Action Test (NAT)—a standard version (ST-NAT), and a user-centered version (UC-NAT) that incorporated environmental adaptations designed to facilitate task performance. The NAT conditions were counterbalanced across participants. Analyses compared performance between the NAT versions and examined the cognitive correlates of each NAT condition. Individuals with schizophrenia made fewer errors on the UC-NAT as compared to the ST-NAT; this between-group difference was significant for all error types. Compared to the ST-NAT, the UC-NAT performance was not significantly associated with an executive function measure of planning. Environmental adaptations may be implemented without extensive training to improve everyday action in individuals with chronic schizophrenia. Environmental adaptations that reduce planning demands may be most effective in this population. (JINS, 2015, 21, 319–329)

To examine the association between reasoning through medical treatment decisions and cognition in a sample of patients with brain metastasis. The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (i.e., intact or impaired). Results indicate that measures of episodic memory and processing speed were associated with reasoning. Using these two predictors, actuarial equations were constructed that can be used to help screen for impaired reasoning ability in patients’ with brain metastasis. The equations presented in this study have clinical significance as they can be used to help identify patients at risk for possessing a diminished ability to reason through medical treatment decisions and, thus, are in need of a more comprehensive evaluation of their medical decision-making capacity. (JINS, 2015, 21, 412–418)

There is evidence to suggest that social skills, such as the ability to understand the perspective of others (theory of mind), may be affected by childhood traumatic brain injuries; however, studies to date have only considered moderate and severe traumatic brain injury (TBI). This study aimed to assess theory of mind after early, mild TBI (mTBI). Fifty-one children who sustained mTBI between 18 and 60 months were evaluated 6 months post-injury on emotion and desires reasoning and false-belief understanding tasks. Their results were compared to that of 50 typically developing children. The two groups did not differ on baseline characteristics, except for pre- and post-injury externalizing behavior. The mTBI group obtained poorer scores relative to controls on both the emotion and desires task and the false-belief understanding task, even after controlling for pre-injury externalizing behavior. No correlations were found between TBI injury characteristics and theory of mind. This is the first evidence that mTBI in preschool children is associated with theory of mind difficulties. Reduced perspective taking abilities could be linked with the social impairments that have been shown to arise following TBI. (JINS, 2015, 21, 483–493)

This study aimed at comparing neuropsychological test scores in 83 cardiologists and nurses (exposed group, EG) working in the cardiac catheterization laboratory, and 83 control participants (non exposed group, nEG), to explore possible cognitive impairments. The neuropsychological assessment was carried out by means of a battery called “Esame Neuropsicologico Breve.” EG participants showed significantly lower scores on the delayed recall, visual short-term memory, and semantic lexical access ability than the nEG ones. No dose response could be detected. EG participants showed lower memory and verbal fluency performances, as compared with nEG. These reduced skills suggest alterations of some left hemisphere structures that are more exposed to IR in interventional cardiology staff. On the basis of these findings, therefore, head protection would be a mandatory good practice to reduce effects of head exposure to ionizing radiation among invasive cardiology personnel (and among other exposed professionals). (JINS, 2015, 21, 670–676)

Aerobic exercise training has been shown to attenuate cognitive decline and reduce brain atrophy with advancing age. The extent to which resistance exercise training improves cognition and prevents brain atrophy is less known, and few studies include long-term follow-up cognitive and neuroimaging assessments. We report data from a randomized controlled trial of 155 older women, who engaged in 52 weeks of resistance training (either once- or twice-weekly) or balance-and-toning (twice-weekly). Executive functioning and memory were assessed at baseline, 1-year follow-up (i.e., immediately post-intervention), and 2-year follow-up. A subset underwent structural magnetic resonance imaging scans at those time points. At 2-year follow-up, both frequencies of resistance training promoted executive function compared to balance-and-toning (standardized difference [d]=.31–.48). Additionally, twice-weekly resistance training promoted memory (d=.45), reduced cortical white matter atrophy (d=.45), and increased peak muscle power (d=.27) at 2-year follow-up relative to balance-and-toning. These effects were independent of one another. These findings suggest resistance training may have a long-term impact on cognition and white matter volume in older women. (JINS, 2015, 21, 745–756)

The frontoparietal control network, anatomically and functionally interposed between the dorsal attention network and default mode network, underpins executive control functions. Individuals with attention-deficit/hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions, which are mainly mediated by the frontoparietal control network. Involvement of the frontoparietal control network based on the anterior prefrontal cortex in neurobiological mechanisms of ADHD has yet to be tested. We used resting-state functional MRI and seed-based correlation analyses to investigate functional connectivity of the frontoparietal control network in a sample of 25 children with ADHD (7–14 years; mean 9.94±1.77 years; 20 males), and 25 age-, sex-, and performance IQ-matched typically developing (TD) children. All participants had limited in-scanner head motion. Spearman’s rank correlations were used to test the associations between altered patterns of functional connectivity with clinical symptoms and executive functions, measured by the Conners’ Continuous Performance Test and Spatial Span in the Cambridge Neuropsychological Test Automated Battery. Compared with TD children, children with ADHD demonstrated weaker connectivity between the right anterior prefrontal cortex (PFC) and the right ventrolateral PFC, and between the left anterior PFC and the right inferior parietal lobule. Furthermore, this aberrant connectivity of the frontoparietal control network in ADHD was associated with symptoms of impulsivity and opposition-defiance, as well as impaired response inhibition and attentional control. The findings support potential integration of the disconnection model and the executive dysfunction model for ADHD. Atypical frontoparietal control network may play a pivotal role in the pathophysiology of ADHD. (JINS, 2015, 21, 271–284)

The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (FICV(3,877)=11.25; p<.0001; FPacedTiming(3,877)=22.89; p<.0001). When prodromal HD participants closest to HD diagnosis were compared to controls, Cohen’s d effect sizes were larger in magnitude for the within-task variability measure, paced timing (−1.01), and the SDMT (−0.79) and paced tapping coefficient of variation (CV) (−0.79) compared to the measures of across-task variability [CV (0.55); intra-individual standard deviation (0.26)]. Across-task variability may be a sensitive marker of cognitive decline in individuals with prodromal HD approaching disease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample. (JINS, 2015, 21, 8–21)

Executive functions (EF) and psychomotor speed (PMS) has been widely studied in Huntington’s disease (HD). Most studies have focused on finding markers of disease progression by comparing group means at different disease stages. Our aim was to investigate performances on nine measures of EF and PMS in a group of premanifest and manifest HD-gene expansion carriers and to investigate which measures were most sensitive for assessment of individual patients by analyzing frequencies of impaired performances relative to healthy controls. We recruited HD gene-expansion carriers, 48 manifest and 50 premanifest and as controls 39 healthy gene-expansion negative individuals. All participants underwent neurological examination and neuropsychological testing with nine cognitive measures. The frequency of impairment was investigated using cutoff scores. In group comparisons the manifest HD gene-expansion carriers scored significantly worse than controls on all tests and in classification of individual scores the majority of scores were classified as probably impaired (10th percentile) or impaired (5th percentile) with Symbol Digit Modalities Test (SDMT) being the most frequently impaired. Group comparisons of premanifest HD gene-expansion carriers and healthy controls showed significant differences on SDMT and Alternating fluency tests. Nevertheless the frequencies of probably impaired and impaired scores on individual tests were markedly higher for Alternating and Lexical fluency tests than for SDMT. We found distinct group differences in frequency of impairment on measures of EF and PMS in manifest and premanifest HD gene-expansion carriers. Our results indicate to what degree these measures can be expected to be clinically impaired. (JINS, 2015, 21, 1–10)

Impairment on inhibitory tasks has been well documented in bipolar disorder (BD). Differences in cerebral blood flow (CBF) between BD patients and healthy comparison (HC) participants have also been reported. Few studies have examined the relationship between cognitive performance and regional CBF in this patient population. We hypothesized that group differences on an inhibitory task (the Delis-Kaplan Executive Function Scale’s Color-Word Inhibition task) would be associated with differential CBF in bilateral anterior cingulate cortex (ACC), inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) regions. Whole brain resting CBF was measured using Multiphase Pseudocontinuous Arterial Spin Labeling MR imaging for 28 euthymic BD and 36 HC participants. Total gray matter (GM) CBF was measured, and regional CBF values were extracted for each region of interest (ROI) using Freesurfer-based individual parcellations. Group, CBF, and group-by-CBF interaction were examined as predictors of inhibition performance. Groups did not differ in age, gender or education. BD patients performed significantly worse on Color-Word inhibition. There were no significant group differences in CBF in either total GM or in any ROI. There was a group by CBF interaction in the bilateral ACC, right IPL and right DLPFC such that better inhibitory performance was generally associated with higher resting state CBF in BD subjects, but not HC participants. Although CBF was not abnormal in this euthymic BD sample, results confirm previous reports of inter-episode inhibitory deficits and indicate that the perfusion-cognition relationship is different in BD compared to HC individuals. (JINS, 2015, 21, 105–115)