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PubMedDate not supplied

[Executive dysfunction in Huntington's disease].

INTRODUCTION: In the early stages of Huntington s disease (HD), there is selective vulnerability of the medium-sized spinous cells of the striate nucleus. These cells are connected with the dorsolateral prefrontal cortex, which is an area involved in cognitive processes concerning attention and executive function, forming part of one of the cortico-striatal circuits. OBJECTIVE: To analyze and interpret the executive dysfunction of a group of patients with HD at a moderately advanced stage. PATIENTS AND METHODS: We evaluated 16 patients and controls. Three clinical scales were used: the motor section of the UHDRS, the independence scale and the total functional capacity scale. For cognitive evaluation we used the study protocol of the Core Assessment Program for Intracerebral Transplantation for HD (CAPIT-HD). RESULTS: The patients with EH showed significant deterioration on the tests to evaluate cognitive function, attention and working memory. There were only two exceptions, the WEST and the direct order digit span. CONCLUSIONS: Patients with HD have executive dysfunction, probably due to dysfunction of the cortico-striatal circuits. We therefore agree with the proposal that fronto-striatal cognitive dysfunction is the most suitable name for the cognitive deterioration seen in this condition.

Adult↗

PubMed2005

Cognitive and functional neuroimaging correlate for anosognosia in mild cognitive impairment and Alzheimer's disease.

OBJECTIVES: To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD). METHODS: From a prospective Memory Clinic cohort including consecutively referred patients, age 60 years or above, and with MMSE score 20 or above, 36 patients with AD and 30 with MCI were included in this study. Anosognosia was assessed using a categorical scale and discrepancy scores between patients' and relatives' reports on a 20-item Memory Questionnaire (MQ). Behavioural symptoms were assessed with Frontal Behavioural Inventory (FBI). Executive functions were examined with a range of neuropsychological tests. Tc99m-HMPAO SPECT was obtained in an unselected sample of 55 of the 66 patients, and rCBF was analysed in six cortical frontal regions. RESULTS: Insight was equally impaired in the two patient groups. A significant correlation was found between impaired awareness and dementia severity (MMSE). Discrepancy-scores on the MQ were significantly correlated to scores on FBI and to rCBF in the right inferior frontal gyrus, but not to executive tests. The groups classified by the categorical ratings 'full', 'shallow' and 'no' awareness were not characterized by differences in behavioural symptoms, executive performance or frontal rCBF. CONCLUSIONS: Impaired awareness is associated with behavioural symptoms and may reflect functional impairment in the right inferior frontal cortex.

Aged↗

PubMed2006

Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test.

The specific role of particular cerebral regions with regard to executive functions remains elusive. We conducted a functional magnetic resonance imaging (fMRI) study to segregate different network components underlying the Wisconsin Card Sorting Test (WCST), a test widely applied clinically to assess executive abilities. Three different test variants of the WCST, differing in task complexity (A > B > C), were contrasted with a high-level baseline condition (HLB). Cognitive subcomponents were extracted in a serial subtraction approach (A-C, A-B, B-C). Imaging data were further subjected to a correlational analysis with individual behavioral parameters. Contrasting A with the HLB revealed the entire neural network underlying WCST performance, including frontoparietal regions and the striatum. Further analysis showed that, within this network, right ventrolateral prefrontal cortex related to simple working memory operations, while right dorsolateral prefrontal cortex related to more complex/manipulative working memory operations. The rostral anterior cingulate cortex (ACC) and the temporoparietal junction bilaterally represented an attentional network for error detection. In contrast, activation of the caudal ACC and the right dorsolateral prefrontal cortex was associated with increased attentional control in the context of increasing demands of working memory and cognitive control. Non-frontal activations were found to be related to (uninstructed relative to instructed) set-shifting (cerebellum) and working memory representations (superior parietal cortex, retrosplenium). The data provide neural correlates for the different cognitive components involved in the WCST. They support a central role of the right dorsolateral prefrontal cortex in executive working memory operations and cognitive control functions but also suggest a functional dissociation of the rostral and caudal ACC in the implementation of attentional control.

Brain↗

PubMed1996

Imitation and pantomime in high-functioning adolescents with autism spectrum disorders.

A study was designed to test 2 alternative hypotheses--a symbolic hypothesis and an executive function hypotheses--for the imitation and pantomime deficits found in previous studies of autism. The subjects were 17 adolescent high-functioning subjects with autism spectrum disorders and 15 clinical comparison subjects who were matched on chronological age and verbal IQ. Meaning and sequence were manipulated in facial and manual imitation tasks. Sequence was manipulated in the pantomime and control tasks. Recognition memory and motor control tasks were matched to the experimental tasks. The results provided no support for the symbolic deficit hypothesis; meaning aided rather than hindered the performance of the group with autism. Partial support for the executive deficit hypothesis was found. There were no group differences on motor control tasks, and few on the memory control tasks, arguing against deficits in motor initiation, basic motor coordination, or visual recognition memory.

Adolescent↗

PubMed2006

Neuropsychological changes in patients with primary lateral sclerosis.

Primary lateral sclerosis (PLS) has been defined as rare, and the neuropsychological changes remain poorly defined. We studied 20 patients with a diagnosis of PLS. We carried out an extensive psychometric testing including a general assessment (memory, language, attention, visual-constructional ability and praxis) and a more specific assessment of prefrontal and premotor cortex functions in order to characterize the neuropsychological profile of the patients compared to matched controls, and explore executive functions and premotor cortex functions. None of the PLS patients was demented but they all presented memory deficits reflecting an executive dysfunction. All patients but three had signs of premotor and/or prefrontal cortex deficits. The cognitive impairment in PLS, specifically related to a frontal lobe dysfunction, seems qualitatively similar to ALS. Our results suggest a patchy distribution of cortical involvement in PLS but it remains difficult to draw any definite conclusion as to the spatio-temporal progression of the disease into the different regions of the frontal lobe.

Adult↗

PubMed1997

Impaired upper limb coordination in alcoholic cerebellar degeneration.

BACKGROUND: Alcoholic cerebellar degeneration (ACD) is a disorder resulting from severe chronic alcoholism and malnutrition and is characterized by cognitive disturbances, ataxia of gait, and truncal instability, with generally preserved coordination of the upper extremities. OBJECTIVES: To determine whether cognitive deficits in patients with ACD are the same as those seen in patients with severe chronic alcoholism without ACD and to determine whether upper limb motor coordination is different in the 2 groups. DESIGN: We examined cognitive function and upper limb coordination in 56 patients with severe chronic alcoholism, 13 with ACD and 43 without ACD, who had comparable levels of total alcohol intake. Neuropsychological and motor function was measured using an expanded Halstead-Reitan Neuropsychological Test Battery, including the Tactual Performance Test and Grooved Pegboard Test. RESULTS: Neither group had impaired coordination of upper limb function on clinical neurological examination. Both groups had impaired performance on neuropsychological tests involving executive function, but the patients with ACD had greater impairment of upper limb coordination than the patients without ACD as measured by the Tactual Performance Test and Grooved Pegboard Test. CONCLUSIONS: The findings suggest that these 2 groups have similar cognitive deficits but that upper extremity motor functions are more significantly impaired in the ACD group and that quantitative tasks of motor function reveal these impairments.

Alcoholism↗

PubMed2003

Diazepam produces disinhibitory cognitive effects in male volunteers.

RATIONALE: Diazepam has well known amnestic and sedative effects but effects on fronto-executive function remain largely uninvestigated, especially on neuropsychologically validated tests of risk taking and orbitofrontal cortex function. OBJECTIVES: We aimed to determine the impact of diazepam on a variety of executive tasks. METHODS: The effects of 5, 10 and 20 mg of diazepam on a battery of neuropsychological tests were investigated using a randomised, double blind, placebo-controlled design. Seventy-five adult men were recruited. The Rogers et al. (1999b) test of risk-taking was given along with tasks from the CANTAB battery. RESULTS: Diazepam impaired performance on the Tower of London test of planning, without influencing visual pattern recognition memory. Subjects who had taken diazepam made more risky choices on the risk-taking task. On two speeded reaction time tasks diazepam impaired discrimination sensitivity and increased the bias to respond. CONCLUSIONS: In contrast to the well-known sedative effects of diazepam, we demonstrate disinhibitory effects on two speeded reaction time tasks. Our results show that diazepam can impair performance on reaction time tasks both by impairing sensitivity and by increasing the bias to respond. Furthermore diazepam impaired performance on tests of planning and risky decision making that depend predominantly on dorsolateral and orbitofrontal regions of the prefrontal cortex, respectively.

Adult↗

PubMed1994

Systematized delusions and neuropsychological function in paranoid and nonparanoid schizophrenia.

We extended research originating with the Tsuang-Winokur criteria for paranoid and nonparanoid schizophrenia. To partially resolve problems of subtype instability, 41 consecutive admissions meeting DSM-III-R criteria for schizophrenia were subdivided according to whether they ever experienced prominent systematized delusions. Neuropsychological profiles for paranoid patients and nonparanoids with a history of systematized delusions were extremely similar. When combined, this 'systematized' group had significantly better general verbal ability and verbal memory than patients who never manifested systematized delusions. There was also a significant neuropsychological function-by-group interaction. The neuropsychological data suggested that systematized patients had better premorbid cognitive functioning as well as a greater discrepancy between premorbid verbal ability and current attentional functioning. No between-group differences were found on a measure of prefrontal-executive function, nor were there any neuropsychological differences between traditionally defined (DSM-III-R) paranoid and nonparanoid subgroups. This study suggests a possible shift in the dividing line between paranoid and nonparanoid subtypes and illustrates the potential value of neuropsychological data for refining psychiatric nosologies.

Adult↗

PubMed2006

Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond.

This review summarizes our current understanding of catechol-o-methyltransferase (COMT) and how it relates to brain function and schizophrenia. We begin by considering the COMT gene, its transcripts and proteins, and its relevance for central catecholamine function. We then describe how variation in COMT activity affects the function of the prefrontal cortex (PFC) and associated areas, reviewing evidence that COMT modulates executive function and working memory and highlighting recent data that also implicate it in emotional processing. Finally, we discuss briefly the genetic association between COMT and schizophrenia, focusing in particular on the complex interaction of functional loci within the gene that may underlie the mixed results of studies to date. We conclude by outlining preliminary data indicating that COMT is a promising therapeutic target for ameliorating the cognitive deficits associated with schizophrenia.

Amino Acid Substitution↗

PubMed2006

Random number generation as an index of controlled processing.

Random number generation (RNG) is a functionally complex process that is highly controlled and therefore dependent on Baddeley's central executive. This study addresses this issue by investigating whether key predictions from this framework are compatible with empirical data. In Experiment 1, the effect of increasing task demands by increasing the rate of the paced generation was comprehensively examined. As expected, faster rates affected performance negatively because central resources were increasingly depleted. Next, the effects of participants' exposure were manipulated in Experiment 2 by providing increasing amounts of practice on the task. There was no improvement over 10 practice trials, suggesting that the high level of strategic control required by the task was constant and not amenable to any automatization gain with repeated exposure. Together, the results demonstrate that RNG performance is a highly controlled and demanding process sensitive to additional demands on central resources (Experiment 1) and is unaffected by repeated performance or practice (Experiment 2). These features render the easily administered RNG task an ideal and robust index of executive function that is highly suitable for repeated clinical use.

Adult↗

PubMed2005

Years of severe and isolated amnesia can precede the development of dementia in early-onset Alzheimer's disease.

A young patient with a severe and isolated memory disorder, meeting the criteria for MCI, was followed for a period of 8 years. His overall functional level remained stable with a CDR-score at 0.5 until the last year when it dropped to 1.0. Neuropsychological testing showed severe memory deficits but otherwise normal cognitive functions. Only minimal progression was measured; however, the last testing showed impaired abstraction and executive functioning as well as discrete problems generating names of objects and people. Neuroimaging, with MRI and SPECT, was consistent with a progressive degenerative disorder, and cerebrospinal fluid levels of beta-amyloid 1-42, tau protein, and phosphorylated tau protein were characteristic of Alzheimer's disease (AD). We argue that this is a case of prodromal AD, which illustrates an extreme version of the normal course with respect to slow progression of the disease and severity of amnesia early in the course.

Alzheimer Disease↗

PubMed2006

Cognitive functions among Hong Kong Chinese people with schizophrenia.

Persons with schizophrenia show deficits in a variety of cognitive domains including executive function, attention, memory and language. Similar interest in studying the impact of cognitive deficits on the everyday functioning of people with schizophrenia has been documented. This study examined the cognitive functioning among Hong Kong Chinese schizophrenic patients compared with other patient groups, and its relationship with functional outcome, especially in the social aspect. Results indicated that schizophrenic patients presented with mild cognitive problems compared with neurosurgical and demented patients. Initial support was found in relating cognitive functions, as measured by Neurobehavioral Cognitive Status Examination, with functional outcome as measured by Functional Independence Measures. The implication for community rehabilitation is also discussed.

Aged↗

PubMed2000

Dysexecutive syndrome in schizophrenia: A cross-cultural comparison between Japanese and British patients.

This study tested the hypothesis that the dysexecutive syndrome of schizophrenia is impervious to cultural differences. 18 Japanese and 22 British patients and 14 Japanese and 19 British control subjects were compared on the BADS (Behavioural Assessment of Dysexecutive Syndrome), a comprehensive neuropsychological assessment battery, designed for 'ecological validity', and other measures of frontal executive functions (EFs). Both cultural groups of schizophrenic patients showed equally severe impairment in most executive tests including the BADS (verbal fluency and intelligence were less impaired). Irrespective of cultural origin, similar neuropsychological deficits were found in patients with minimal intellectual deterioration. Our study suggests that socio-cultural background does not affect the dysexecutive profile of schizophrenia very much, and that neuropsychological assessment may possibly provide added clinical information relevant to the management and rehabilitation of schizophrenic patients across different cultures.

Journal Article↗

PubMed2006

Cognition and the sex chromosomes: studies in Turner syndrome.

Turner syndrome (TS) is a human genetic disorder involving females who lack all or part of one X chromosome. The complex phenotype includes ovarian failure, a characteristic neurocognitive profile and typical physical features. TS features are associated not only with complete monosomy X but also with partial deletions of either the short (Xp) or long (Xq) arm (partial monosomy X). Impaired visual-spatial/perceptual abilities are characteristic of TS children and adults of varying races and socioeconomic status, but global developmental delay is uncommon. The cognitive phenotype generally includes normal verbal function with relatively impaired visual-spatial ability, attention, working memory, and spatially dependent executive function. The constellation of neurocognitive deficits observed in TS is most likely multifactorial and related to a complex interaction between genetic abnormalities and hormonal deficiencies. Furthermore, other determinants, including an additional genetic mechanism, imprinting, may also contribute to cognitive deficits associated with monosomy X. As a relatively common genetic disorder with well-defined manifestations, TS presents an opportunity to investigate genetic and hormonal factors that influence female cognitive development. TS is an excellent model for such studies because of its prevalence, the well-characterized phenotype, and the wealth of molecular resources available for the X chromosome. In the current review, we summarize the hormonal and genetic factors that may contribute to the TS neurocognitive phenotype. The hormonal determinants of cognition in TS are related to estrogen and androgen deficiency. Our genetic hypothesis is that haploinsufficiency for gene/genes on the short arm of the X chromosome (Xp) is responsible for the hallmark features of the TS cognitive phenotype. Careful clinical and molecular characterization of adult subjects missing part of Xp links the TS phenotype of impaired visual spatial/perceptual ability to specific distal Xp chromosome regions. We demonstrate that small, nonmosaic deletion of the distal short arm of the X chromosome in adult women is associated with the same hallmark cognitive profile seen in adult women with TS. Future studies will elucidate the cognitive deficits and the underlying etiology. These results should allow us to begin to design cognitive interventions that might lessen those deficits in the TS population.

Adult↗

PubMedDate not supplied

Neuropsychological deficits in vascular dementia in relation to Alzheimer's disease: reviewing evidence for functional similarity or divergence.

The hypothesis that vascular dementia (VAD) may be associated with a specific pattern of neuropsychological dysfunction as compared to Alzheimer's disease (AD) is reviewed. The empirical findings were evaluated with regard to methodology, most importantly the comparability between groups regarding demographic variables and severity of dementia. They were also classified according to the cognitive and sensory-motor functions affected. No consistent differences were found between VAD and AD patients in neuropsychological performance testing general cognitive functioning, syntax, verbal comprehension, visuospatial tasks, and primary as well as semantic memory, indicating a functional similarity between VAD and AD. However, inferior performance was found for VAD in executive functioning, verbal fluency, attention, and motor performance. Superior performance for VAD was found in naming and with regard to intrusion errors. The findings on episodic memory were inconclusive. These results should be considered in light of possible selection bias due to the fact that all studies used a hospital-based sample of subjects and not subjects from the community. Bias may also arise from the variations in lesion site, size, number, and timing between different VAD groups. Third, the risk of confounding errors due to a lack of comparability between etiological groups in terms of demographic variables as well as cognitive decline cannot be excluded. Future studies should take into account variation in the severity of cognitive decline, variation regarding lesion characteristics, etiological factors, and subtypes of VAD in order to increase our knowledge about the functional features of VAD.

Aged↗

PubMed2000

Clinical and neuropsychological profiles of obsessive-compulsive schizophrenia: a pilot study.

This pilot study compared characteristics of obsessive-compulsive (OC) schizophrenic patients and a matched non-OC schizophrenic control group. The OC-schizophrenic group required more intensive clinical interventions and had a poorer clinical course, lower levels of functioning, and longer periods of hospitalization. They showed greater negative symptoms and more impaired executive functioning. These findings suggest OC-schizophrenic patients may have an atypical set of clinical and neuropsychiatric characteristics, perhaps constituting a subgroup within the schizophrenia spectrum. Pathophysiology and possible treatment implications require further study.

Adult↗

PubMed2002

Sustained attention deficit in bipolar disorder.

BACKGROUND: Recovery in bipolar disorder is central to its definition but is rarely complete. Previous work has suggested that neuropsychological impairment persists during the euthymic state but has been confounded partly by mild affective symptoms in remitted patients. AIMS: To characterise neuropsychological functioning in the euthymic phase of bipolar disorder with an emphasis on tasks of executive functioning. METHOD: Thirty euthymic patients with bipolar disorder were compared with thirty healthy controls on neuropsychological tasks differentially sensitive to damage within prefrontal cortex. RESULTS: Bipolar I patients were impaired on tasks of attentional set shifting, verbal memory and sustained attention. Only sustained attention deficit survived controlling for mild affective symptoms. This deficit was related to progression of illness, but was none the less present in a subgroup of patients near illness onset. CONCLUSIONS: Sustained attention deficit may represent a neuropsychological vulnerability marker for bipolar disorder, providing a focus for further understanding of the phenotype and analysis of the neuronal networks involved.

Adolescent↗

PubMedDate not supplied

[Cognitive impairment in multiple sclerosis patients].

In addition to neurological symptoms, multiple sclerosis is characterized by cognitive function impairment. Disturbances of memory, recall, information processing, visual-spacial perception, attention, and executive function, in less extent of speech, are present in about 60% of patients. They are similar to disorders in other subcortical dementias. Once they appear, they rarely recede. Conventional, and especially nonconventional magnetic resonance imaging evaluates more precisely the tissue substrate--diffuse neuroaxonal lesion of the entire brain parenchyma--than clinical findings, already in the early stage of the disease. Alterations in the brain imaging are manifested by T2 hyperintensive and T1 hypointensive lesions, decreased neuronal marker N-acetyl-aspartate in magnetic spectroscopy, decreased magnetization transfer ratio, and increased diffusivity with reduced anisotropy in diffusion-weighted imaging. Total volume of brain lesion, corpus callosum diameter, and relation of measures of brain chambers and the rest of the brain, are best indices of cognitive dysfunction in multiple sclerosis. Their diagnosis in the very beginning of the disease allows early application of therapeutic procedures. Symptomatic treatment of these disorders is not efficient, and immunomodulation, particularly the use of biologic versions of interferon-beta, shows disputable effects. Cognitive dysfunctions affect relationships and working ability of patients.

Attention Deficit Disorder with Hyperactivity↗