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PubMed2007

Early cognitive deficits in Swedish gene carriers of Huntington's disease.

The primary focus of this study was to examine whether there is early neuropsychological impairment in presymptomatic Huntington's disease (HD). A broad neuropsychological assessment battery was administered to 24 asymptomatic gene carriers (HD+) and 31 noncarriers (HD-). The gene carriers revealed inferior cognitive functioning as compared with the noncarriers in memory and executive functions. When the gene carriers were assigned to 2 groups based on predicted years to onset (with 15 and over being HD+ late and under 15 being HD+ near), the HD+ near group performed significantly worse than the HD+ late group in all domains but ability to shift conceptually and visuospatial memory. Results suggest that early cognitive deficits are detectable prior to motor symptoms, first in memory functions and then in executive functions and perceptual motor speed.

Adult↗

PubMed2006

Distinct neural mechanisms of risk and ambiguity: a meta-analysis of decision-making.

Converging evidence from human and animal studies suggests that decision-making relies upon a distributed neural network based in the frontal lobes. In particular, models of decision-making emphasize the involvement of orbitofrontal cortices (OFC) and the medial wall. While decision-making has been studied broadly as a class of executive function, recent models have suggested the differentiation between risky and ambiguous decision-making. Given recent emphasis on the role of OFC in affectively laden "hot" executive function and dorsolateral prefrontal cortex (DLPFC) in more purely cognitive "cool" executive function, we hypothesize that the neural substrates of decision-making may differ depending on the nature of the decision required. To test this hypothesis, we used recently developed meta-analytic techniques to examine the existent functional neuroimaging literature. An initial meta-analysis of decision-making, both risky and ambiguous, found significantly elevated probabilities of activation in frontal and parietal regions, thalamus, and caudate. Ambiguous decision-making was associated with activity in DLPFC, regions of dorsal and subcallosal anterior cingulate cortex (ACC), and parietal cortex. Risky decision-making was associated with activity in OFC, rostral portions of the ACC, and parietal cortex. Direct statistical comparisons revealed significant differences between risky and ambiguous decision-making in frontal regions, including OFC, DLPFC, and ACC, that were consistent with study hypotheses. These findings provide evidence for the dissociation of neural circuits underlying risky and ambiguous decision-making, reflecting differential involvement of affective "hot" and cognitive "cool" processes.

Brain↗

PubMed2004

Evaluation of the effect of radiotherapy for pituitary tumours on cognitive function and quality of life.

AIMS: Pituitary tumours are often treated with radiotherapy, which can cause cognitive impairment when given in high doses. It is assumed that current regimens do not cause damage, but this has not been established. The aim was to determine whether radiotherapy given to people with pituitary tumours was associated with cognitive impairment and reduced quality of life. MATERIAL AND METHODS: We retrospectively compared two outcome groups (patients with pituitary tumours who had undergone radiotherapy and surgery and patients with pituitary tumours who had surgery alone), and carried out standardised tests of cognitive function and quality of life. RESULTS: The data suggested that patients with pituitary tumours treated with surgery, with or without radiotherapy, had cognitive impairment compared with the normal population. Patients receiving radiotherapy performed significantly worse than those receiving only surgery on the Stroop test, a measure of executive function. They also scored significantly lower on the Physical Health composite of the SF36, although this difference was no longer significant when account was taken of baseline differences between the groups. There were no significant differences in other cognitive functions, mood, general well-being or the Mental Health Composite of the SF36. CONCLUSIONS: Patients treated for pituitary disease may have cognitive impairment. A decrease in cognitive function was found regardless of treatment type. The decrease seemed to be greater in the radiotherapy group and was mainly on executive function. This impairment of executive function could affect daily life. Further prospective studies are required to assess the effect of pituitary disease on cognitive function and the safety of radiotherapy.

Adult↗

PubMed2004

Deficient saccadic inhibition in Asperger's disorder and the social-emotional processing disorder.

BACKGROUND: Both Asperger's disorder and the social-emotional processing disorder (SEPD), a form of non-verbal learning disability, are associated with executive function deficits. SEPD has been shown to be associated with deficient saccadic inhibition. OBJECTIVE: To study two executive functions in Asperger's disorder and SEPD, inhibition and task switching, using a single saccadic paradigm. METHODS: 22 control subjects and 27 subjects with developmental social processing disorders-SEPD, Asperger's disorder, or both syndromes-performed random sequences of prosaccades and antisaccades. This design resulted in four trial types, prosaccades and antisaccades, that were either repeated or switched. The design allowed the performance costs of inhibition and task switching to be isolated. RESULTS: Subjects with both Asperger's disorder and SEPD showed deficient inhibition, as indicated by increased antisaccade errors and a disproportionate increase in latency for antisaccades relative to prosaccades. In contrast, task switching error and latency costs were normal and unrelated to the costs of inhibition. CONCLUSIONS: This study replicates the finding of deficient saccadic inhibition in SEPD, extends it to Asperger's disorder, and implicates prefrontal cortex dysfunction in these syndromes. The finding of intact task switching shows that executive function deficits in Asperger's disorder and SEPD are selective and suggests that inhibition and task switching are mediated by distinct neural networks.

Adult↗

PubMed2006

Bipolar I patients with and without a history of psychotic symptoms: do they differ in their cognitive functioning?

Recently, many reports have consistently demonstrated cognitive deficits in patients with bipolar disorder (BD), but their relationship with symptomatology, specifically psychotic symptoms, remains unclear. Our main hypothesis was that a history of hallucinations and/or delusions in the course of BD-I is associated with severe cognitive deficits. We investigated several cognitive functions (memory, attention, verbal fluency and executive functions) in 18 BD-I patients with a history of psychotic symptoms (HPS+), 17 BD-I patients without a history of psychotic symptoms (HPS-), 33 schizophrenic patients and 26 healthy control subjects. Both groups of BD-I patients were more impaired than the normal controls in attention, verbal memory, verbal fluency and executive functions. Only HPS+ BD-I patients showed more difficulties in completing the Stroop test than nonpsychotic bipolar patients. Nevertheless, after adjustment for the effects of current psychopathology, this difference disappeared. Schizophrenic subjects showed worse performance than BD-I subjects in verbal memory and verbal fluency. These results suggest that a history of psychotic symptoms in bipolar I disorder may not be associated with more cognitive deficits. Further research on euthymic bipolar patients with and without HPS is required to confirm these findings.

Adolescent↗

PubMed2000

Neuropsychological functioning in first-episode psychosis--evidence of specific deficits.

Neuropsychological impairment is ubiquitous in schizophrenia even at the first presentation of psychotic symptoms. We sought to elucidate the nature of the neuropsychological profile at the onset of the illness by examining the neuropsychological functioning of 40 patients experiencing their first episode of psychosis and 22 matched controls. All participants completed a battery of neuropsychological tasks designed to assess attention, verbal learning/memory, non-verbal memory, spatial ability, psychomotor speed, and executive function. First-episode patients showed significant impairment on tasks of executive function, including those requiring the ability to form and initiate a strategy, to inhibit prepotent responses, and to shift cognitive set, and also on tasks of verbal fluency. Memory impairments were seen on verbal learning and delayed non-verbal memory only. Impairment on tasks of psychomotor speed suggests that there may be a significant amount of cognitive slowing even at the first onset of psychosis. We suggest that our patients may be experiencing difficulty in specific aspects of executive functions, including the ability to form and execute a strategy, and these difficulties may be mediating the deficits observed on tasks of verbal learning.

Adolescent↗

PubMed1998

Disruptive, delinquent and aggressive behavior in female adolescents with a psychoactive substance use disorder: relation to executive cognitive functioning.

OBJECTIVE: This study had four objectives: (1) to determine whether female adolescents with a psychoactive substance use disorder are more impaired than controls on a battery of neuropsychological tests of Executive Cognitive Functioning (ECF); (2) to determine whether these individuals exhibit higher levels of disruptive, delinquent and aggressive behavior compared with controls; (3) to determine whether ECF is related to disruptive, delinquent and aggressive behavior in this population; and (4) to determine whether these relations are moderated by drug use. METHOD: Multiple indicators of ECF, and disruptive, delinquent and aggressive behavior, as well as drug use, were used to test these relations in a sample of 188 female adolescents who qualified for a DSM-III-R diagnosis of a psychoactive substance use disorder (PSUD) and 95 normal controls between the ages of 14-18 years (N = 283). RESULTS: Hierarchical multiple regression equations determined that ECF was related to disruptive, delinquent and aggressive behavior even when chronological age, SES and drug use were accounted for. The final regression models suggested that drug use was more strongly related to disruptive and delinquent behavior, whereas ECF was more strongly related to aggression. Drug use did not moderate any relation between ECF and the dependent measures. CONCLUSIONS: One implication of these results is that violence prevention and treatment outcomes may be ameliorated by incorporating cognitive habilitation of ECF as an integral component of multimodel interventions.

Adolescent↗

PubMed2000

Dissociation of ketamine effects on rule acquisition and rule implementation: possible relevance to NMDA receptor contributions to executive cognitive functions.

BACKGROUND: The demands of the Wisconsin Card Sorting Test (WCST) change with experience. This report contains two studies designed to examine N-methyl-D-aspartate (NMDA) receptor contributions to the executive components of WCST performance. These aspects of WCST performance figure more prominently in the initial completion of this task than in subsequent task repetitions in healthy populations. METHODS: In the first study, healthy subjects (n = 15) completed the WCST on two occasions separated by 1 week. In the second study, healthy subjects (n = 22) completed two test days spaced by approximately 1 week, during which, they completed the WCST and other assessments after administration of the NMDA antagonist ketamine (intravenous bolus 0.26 mg/kg followed by infusion of 0.65 mg/kg/hour) or matched placebo. RESULTS: In the first study, subjects reduced the number of total and perseverative errors with a single repetition of the WCST. In the second study, ketamine significantly increased the number of total errors and the number and percent of perseverative errors on the first, but not the second test day. Similarly, it reduced the number of category criteria met on the first, but not second test day. Ketamine also increased distractibility, impaired recall, produced psychosis, altered perception, and had effects resembling the negative symptoms of schizophrenia. However, only WCST performance showed order dependency. CONCLUSIONS: This order dependency further implicates NMDA receptors in executive cognitive functions associated with the frontal cortex.

Adult↗

PubMed2006

Profile of executive deficits in cocaine and heroin polysubstance users: common and differential effects on separate executive components.

OBJECTIVES: Structure of executive function was examined and we contrasted performance of substance dependent individuals (polysubstance users) and control participants on neuropsychological measures assessing the different executive components obtained. Additionally, we contrasted performance of polysubstance users with preference for cocaine vs heroin and controls to explore possible differential effects of the main substance abused on executive impairment. METHODS: Two groups of participants were recruited: abstinent polysubstance users and controls. Polysubstance users were further subdivided based on their drug of choice (cocaine vs heroin). We administered to all participants a comprehensive protocol of executive measures, including tests of fluency, working memory, reasoning, inhibitory control, flexibility, and decision making. RESULTS: Consistent with previous models, the principal component analysis showed that executive functions are organized into four separate components, three of them previously described: updating, inhibition, and shifting; and a fourth component of decision making. Abstinent polysubstance users had clinically significant impairments on measures assessing these four executive components (with effect sizes ranging from 0.5 to 2.2). Cocaine polysubstance users had more severe impairments than heroin users and controls on measures of inhibition (Stroop) and shifting (go/no go and category test). Greater severity of drug use predicted poorer performance on updating measures. CONCLUSION: Executive functions can be fractionated into four relatively independent components. Chronic drug use is associated with widespread impairment of these four executive components, with cocaine use inducing more severe deficits on inhibition and shifting. These findings show both common and differential effects of two widely used drugs on different executive components.

Adult↗

PubMed2006

Executive dysfunction in homebound older people with diabetes mellitus.

OBJECTIVES: To describe patterns of cognitive deficits and activities of daily living (ADLs) in older people with diabetes mellitus. DESIGN: Cross-sectional, population-based study. SETTING: Three homecare agency areas in Boston, Massachusetts. PARTICIPANTS: Two hundred ninety-one homebound people aged 60 and older; 40% with diabetes mellitus. MEASUREMENTS: Demographic data; evidence of diabetes mellitus and other diseases; Mini-Mental State Examination and tests of memory and executive function; ADLs. RESULTS: Executive and visuospatial functions were more impaired in individuals with diabetes mellitus than in those without, as assessed using Block Design (mean score+/-standard deviation 17.1+/-8.6 vs 20.5+/-9.6, P=.003) and Trails B (median seconds to accomplish the task: 255 vs 201, P=.03). For memory, word retention score was lower in those with diabetes mellitus than without (39.1+/-28.9 vs 48.0+/-29.7, P=.01), but the other memory tests did not show a difference between these two subgroups. More individuals with diabetes mellitus suffered from depressive symptoms than those without (55% vs 42%, P=.03). The ADL scores of those with diabetes mellitus were higher than those without. CONCLUSION: The pattern of cognitive deficits in people with diabetes mellitus suggests frontal-subcortical dysfunction, as seen in microvascular disease of the brain. The impairment in ADLs may be associated with this executive dysfunction, which cerebral microvascular disease in diabetes mellitus may cause.

Activities of Daily Living↗

PubMedDate not supplied

[Executive dysfunctions in adults with attention deficit hyperactivity disorder].

INTRODUCTION: Several different follow-up studies have shown that attention deficit hyperactivity disorder (ADHD) can persist into adulthood. AIM: To review the findings in adults with ADHD related to alterations in the executive functions. DEVELOPMENT: Research conducted among children with ADHD has revealed the existence of alterations in different tasks that evaluate the executive functions, such as the planning test, sustained attention tasks, cognitive flexibility, verbal fluency and working memory tasks, as well as several inhibition response tasks. In adults with ADHD, despite the lower number of reports in the literature and the methodological shortcomings that exist in some studies, analogous results have also been described with respect to executive functioning, namely, disorders affecting inhibition response, the capacity for planning, difficulties in cognitive flexibility and verbal fluency, and problems with working memory, which include aspects of spatial working memory, logical or visual memory. CONCLUSIONS: The findings we have available at present enable us to confirm the persistence of executive dysfunctions in adult patients with ADHD that are similar to those observed in children with ADHD.

Adult↗

PubMed2026

Role of Polygenic Risk Scores in Predicting Cognitive Functioning after Mild Traumatic Brain Injury: A TRACK-TBI Study.

Patients with traumatic brain injury (TBI) and Glasgow Coma Scale scores of 13-15 (historically called mild TBI [mTBI]) commonly experience changes in cognitive functioning, including processing speed, memory, and executive functioning. In a prospective sample (N = 523) of individuals of European descent who had been treated in a U.S. level 1 trauma center for mTBI, we examined the prognostic value of four polygenic risk scores (PRS) for cognitive outcomes at 6-months postinjury. To estimate the impact of mTBI on cognition, primary cognitive outcomes were scaled as z-scores reflecting changes in performance relative to predicted preinjury performance. The PRS examined were previously developed and validated to predict cognition-related outcomes of educational attainment (Education-PRS), intelligence (Intelligence-PRS), and Alzheimer's disease (AD-mild traumatic brain injury (APOE)-PRS and AD + APOE-PRS). Both the Education-PRS and Intelligence-PRS displayed bivariate associations with all four cognitive outcomes (β = 0.19-0.32), whereas neither Alzheimer's disease PRS was significantly associated with any outcome. After controlling for other factors known to predict cognitive outcomes of TBI (e.g., sex, education, mTBI severity defined by a combination of Glasgow Coma Scale scores and the presence/absence of acute intracranial findings on clinical neuroimaging), the Education-PRS and Intelligence-PRS remained independently predictive of verbal episodic memory (β = 0.10-0.16), whereas their associations with processing speed and executive functioning were mostly nonsignificant and were mediated through educational attainment. Looking across primary z-score and secondary raw score outcomes, cognitive outcomes 6 months post-mTBI were good on average, and PRS made small independent contributions to outcome prediction. The mediation model findings may support theories of cognitive reserve, which propose that individuals with stronger preinjury cognitive processing abilities (often estimated by educational history) can better compensate for TBI. Moreover, findings indicate that PRS may contribute modestly to multivariable models predicting cognitive function after TBI.

Humans↗

PubMed2000

Electrodermal hyporeactivity and antisocial behavior: does anxiety mediate the relationship?

Electrodermal hyporeactivity in the anticipation of aversive stimuli is a highly reliable correlate of diagnosed psychopathy and undersocialized aggressive conduct disorder (UACD), and it has been interpreted as reflecting a weak behavioral inhibition system (BIS) as conceptualized in Gray's work (e.g., in: Royce, J.R. (Ed.), Multivariate Analysis and Psychological Theory. Academic Press, New York, NY, p. 409, 1973). This interpretation predicts that electrodermal hyporeactivity should be associated with a single dimension of temperament involving both low anxiety and behavioral disinhibition. However, temperament scales identify separate dimensions of trait anxiety/neuroticism and inhibitory control, and most investigators have assumed that the BIS is associated with the trait anxiety/neuroticism dimension. The present review supports the view that electrodermal hyporeactivity is associated with both low anxiety and disinhibition, as expected, and, possibly, with poor control of emotional expression. Additionally, electrodermal hyporeactivity appears to relate to an impulsivity dimension among psychopaths rather than to the core personality features of psychopathy. Recent findings raise the possibility that psychopaths suffer from a broader deficit (sometimes described as an executive function deficit) than a weak BIS and that electrodermal hyporeactivity might relate to this broader deficit. It is proposed that problems with impulsivity are more strongly documented than the broader concept of executive function deficits and that a primary disinhibition can produce secondary executive function deficits. A disinhibitory deficit is consistent with the weak BIS hypothesis. Overall, the results appear to be consistent with the electrodermal hyporeactivity-weak BIS hypothesis, but many issues remain to be resolved.

Antisocial Personality Disorder↗

PubMed1996

Executive cognitive functioning and aggressive behavior in preadolescent boys at high risk for substance abuse/dependence.

OBJECTIVE: This study had three purposes; (1) to assess the underlying factor structure of a battery of neuropsychological tests putatively measuring executive cognitive functioning (ECF) in a sample of boys at high and low risk for substance abuse/dependence; (2) to assess the relationship between ECF and aggressive behavior; and (3) to determine the interactive effects of ECF and a family history (FH) of substance dependence on aggressive behavior. METHOD: Multiple measures of ECF and aggressive behavior were used to test these relationships in a sample of 291 10-12 year old boys with and without a FH of substance dependence. RESULTS: Analyses indicated that the measures of ECF loaded on one factor. ECF was related to aggressive behavior even when accounting for IQ and SES. The interaction between ECF and a FH of substance dependence was also associated with aggressive behavior. CONCLUSIONS: The central finding of this investigation indicates that ECF and its interaction with a FH of substance dependence are associated with aggressive behavior. These results suggest that violence prevention and treatment efforts in high risk groups should incorporate cognitive habilitation focusing on training in ECFs.

Adolescent↗

PubMed2003

Neuropsychological effects of treatments for adults with cancer: a meta-analysis and review of the literature.

A meta-analysis was conducted to evaluate possible neuropsychological effects of treatments for cancer in adults. A search revealed 30 studies, encompassing 29 eligible samples, and leading to inclusion of a total of 838 patients and control participants. A total of 173 effect sizes (Cohen's d) were extracted across 7 cognitive domains and as assessed in the literature via 3 methods of comparison (post-treatment compared with normative data, controls, or baseline performance). Statistically significant negative effect sizes were found consistently across both normative and control methods of comparison for executive function, verbal memory, and motor function. The largest effects were for executive function and verbal memory normative comparisons (-.93 and -.91, respectively). When limiting the sample of studies in the analyses to only those with relatively "less severe" diagnoses and treatments, the effects remained. While these results point toward some specific cognitive effects of systemic cancer therapies in general, no clear clinical implications can yet be drawn from these results. More research is needed to clarify which treatments may produce cognitive decrements, the size of those effects, and their duration, while ruling out a wide variety of possible mediating or moderating variables.

Adult↗

PubMed2006

COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia.

Preliminary evidence suggests that a single nucleotide polymorphism (SNP), the val108/158met SNP, within the gene that codes for catechol-O-methyltransferase (COMT), a key enzyme involved in regulating dopamine (DA) transmission within the prefrontal cortex (PFC), is related to cognitive function in schizophrenia and cognitive improvement with atypical antipsychotic drugs (APDs). Specifically, several studies have identified an association between working memory and executive functions, and COMT val108/158met genotype in schizophrenia; although there have been several negative findings that are likely related to small sample sizes and, possibly, medication status of patients at the time of testing. The association between COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine was investigated in a relatively large prospective sample of patients with schizophrenia, most of whom were unmedicated at baseline. Patients were genotyped for the COMT val108/158met SNP after completing a cognitive battery consisting of tests of attention, working memory, verbal learning and memory, executive function, and verbal fluency at baseline and after 6 weeks and 6 months of treatment with clozapine. Consistent with several previous studies, an association between COMT genotype and tests of executive function and working memory was identified at baseline. In addition, a novel interaction between genotype and improvement on tests of attention and verbal fluency was identified. Specifically, met homozygous and val/met heterozygous patients demonstrated significantly greater improvement than val homozygous patients following 6 months of treatment with clozapine. The results are discussed in relation to previous cross-sectional studies and prospective investigations of the associations between COMT genotype, cognition, and cognitive improvement with atypical APDs in schizophrenia.

Adult↗

PubMed2005

The effects of total sleep deprivation on the generation of random sequences of key-presses, numbers and nouns.

According to a recent hypothesis, executive functions should be particularly vulnerable to the effects of total sleep deprivation. Random generation is a task that taps executive functions. In three experiments we examined the effects of total sleep deprivation on random generation of key-presses, numbers, and nouns, in particular on the suppression of prepotent responses and the selection of next responses by way of applying a local-representativeness heuristic. With random key-presses suppression of prepotent responses did not suffer from lack of sleep, but it became poorer at a sufficiently high pacing rate. In contrast, suppression of prepotent responses suffered when numbers and nouns were generated. According to these findings different types of random generation tasks involve different types of inhibitory process. With only four response alternatives, but not with larger response sets, application of the local-representativeness heuristic was impaired after a night without sleep. In terms of a simple formal model, serial-order representations of the preceding responses are used in selecting the next response only for the small response set, and not for larger response sets. Thus, serial-order representations are likely to suffer from loss of sleep. These findings strongly suggest that random generation involves multiple processes and that total sleep deprivation does not impair all sorts of executive functions, but only some.

Adult↗

PubMed2004

Neurocognitive functioning and quality of life among dually diagnosed and non-substance abusing schizophrenia inpatients.

The aim of this study was to compare the domains of intellectual, memory and executive functions of persons with schizophrenia who concurrently have substance abuse disorders (the dually diagnosed) with a group of non-substance-abusing patients with schizophrenia and to ascertain if there were differences between the two groups in their perceptions of quality of life. Neuropsychological and quality of life data of 46 dually diagnosed and 43 non-substance-abusing patients with schizophrenia was analysed retrospectively. All subjects were inpatients of a state psychiatric hospital. Selected subtests of the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale-III constituted the intellectual and memory measures whilst the measures of executive functioning were the Stroop Color Word Test, the FAS version of the Controlled Oral Word Association Test, and the Trail Making Test (Trails A & B). Perceptions of quality of life were evaluated using the World Health Organization Quality of Life measure. The two groups did not differentiate on intellectual and memory domains, however, the dually diagnosed showed a significantly better facility with tasks of executive functions. In addition, the dually diagnosed expressed higher levels of satisfaction with their quality of life compared to the non-substance-abusing patients with schizophrenia. These results have implications for interventions.

Adult↗