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Blood DHEAS concentrations correlate with cognitive function in chronic schizophrenia patients: a pilot study.

There is evidence that neurosteroids such as DHEA and its sulfated form DHEAS can modulate cognitive function. We hypothesize that DHEA/S concentrations may be linked to cognitive impairment in schizophrenia. The aim of this pilot study was to test this hypothesis by examining the relationship between blood levels of DHEAS and cognitive function. The performance of 26 stable medicated chronic schizophrenia patients in a range of neuropsychological domains including verbal memory (Wechsler Memory Scale), executive function (AIM), memory of faces (PFMT), memory for objects (VOLT) and identification of facial emotional expressions (PEAT) was assessed. Single morning blood samples were assayed for levels of DHEAS and cortisol. Significant associations were found between DHEAS levels and DHEAS/Cortisol ratio and verbal memory, executive function and memory for faces. The relationship was independent of the age related reduction in DHEAS levels. These preliminary results suggest that DHEAS may be associated with cognitive impairment in schizophrenia.

Adult↗

Behavioural changes after closed head injury. A neuropsychological issue.

The long-term behavioural consequences of moderate to severe closed head injury (CHI) have been examined within a neuropsychological framework. It is argued that neuropsychological assessment must be considered if the behavioural sequelae of a brain injury are to be fully appreciated and assessment and rehabilitation modules appropriately formulated. Functioning of the frontal lobes is emphasised because this is the area most at risk when a head injury occurs. The meaning of 'executive functions' is examined, and the behavioural and rehabilitation implications of an impaired 'executor' are discussed. It is demonstrated that traditional individual and family-based psychotherapeutic techniques are inappropriate for people with impaired executive functions.

Behavior↗

Real-life-type problem solving in Tourette syndrome.

OBJECTIVE: The main objective of the study was to examine social problem solving in real-life-type situations in Tourette syndrome (TS). BACKGROUND: Studies of cognitive functioning in TS have usually focused on nonsocial, abstract tasks, with mixed findings as to whether there is evidence of impairment in executive functions in those without comorbid disorders. The current study focuses primarily on social functioning, using a problem-solving task known to be sensitive to frontal lobe lesions. METHODS: TS participants without comorbid diagnoses were compared with matched healthy control participants on a problem-solving task, using a range of interpersonal problem scenarios presented on video. A set of more abstract executive tests was also included. RESULTS: Participants with TS were found to perform below a matched control group on the problem-solving task both in generating a range of potential problem solutions, and in selecting appropriate final solutions. They also performed more poorly on aspects of executive function. CONCLUSIONS: This study provides evidence of difficulties in both social and nonsocial aspects of functioning in TS. The implications of the findings for our understanding of TS and problem solving are discussed.

Adult↗

Cognitive functioning in siblings discordant for schizophrenia.

OBJECTIVE: The objective of this study was to investigate neuropsychological impairment as a genetically mediated risk indicator for schizophrenia while accounting for prevalence of schizotypy signs/symptoms in siblings. METHOD: Cognitive functioning in 25 individuals with schizophrenia, 25 unaffected siblings and 25 unrelated healthy controls, was assessed using neuropsychological tests of sustained attention, memory and learning, executive function, visual-spatial ability and psychomotor performance. RESULTS: Unaffected siblings demonstrated better performance than patients on some measures of memory and learning and executive function. Patients and siblings demonstrated impaired Full Scale IQ and verbal fluency, otherwise siblings performed similarly to healthy controls. Controlling for differences in IQ, the shared deficit in verbal fluency disappeared. CONCLUSION: Patients with schizophrenia and unaffected siblings (without schizotypy personality disorder) shared a neuropsychological deficit in verbal fluency. This deficit appeared to be mediated by IQ. Deficits, which differentiated patients from controls, may not be inherited and perhaps are related to the manifestation or treatment of schizophrenia.

Adult↗

Neurodevelopmental effects of postnatal lead exposure at very low levels.

This study is among the first to examine specific neurobehavioral deficits in children exposed at very low lead levels. A systematic analysis for the presence of a threshold of lead exposure was conducted. The sample consisted of 246 African American, inner-city children from whom blood lead concentrations were assessed at 7.5 years of age. The results consistently show neurobehavioral deficits in relation to low levels of lead in the areas of intelligence, reaction time, visual-motor integration, fine motor skills, attention, including executive function, off-task behaviors, and teacher-reported withdrawn behaviors. Effects were identified in the specific domains of attention, executive function, visual-motor integration, social behavior, and motor skills, which have been previously suggested as part of lead's "behavioral signature". Visual inspection of nonparametric regression plots suggested a gradual linear dose-response relation for most endpoints. No threshold discontinuity was evident. Regression analyses in which lead exposure was dichotomized at 10 microg/dl were no more likely to be significant than analyses dichotomizing exposure at 5 microg/dl. Given that associations were found between lead levels as low as 3 microg/dl for multiple outcomes, these data provide additional evidence that there is no apparent lower bound threshold for postnatal lead exposure.

Adult↗

Inhibition of ongoing responses in patients with traumatic brain injury.

In addition to slowness of information processing, it is often assumed that executive functions are deficient in patients with traumatic brain injuries (TBI). The aim of this study was to investigate a specific executive function, the inhibition of ongoing responses in TBI. Twenty-seven patients with TBI and 27 orthopedic patients (OC) performed the stop signal task, which allows the estimation of the time it takes to inhibit an ongoing response. Contrary to expectations, patients with TBI did not perform worse than the OC in the inhibition of ongoing responses. Furthermore, subgroups of the TBI, with frontal and nonfrontal lesions, and with focal versus diffuse damage, did not show any differences in performance. None of the clinical, demographic or neuropsychological data had a significant relationship to inhibition time, apart from age, which showed a significant relationship only in the TBI. It seems likely that deficits in the inhibition of ongoing responses are not very common after TBI.

Adolescent↗

Neuropsychological outcome of children with intrauterine growth restriction: a 9-year prospective study.

OBJECTIVE: The aim was to evaluate the effect of late-onset intrauterine growth restriction on the neuropsychological profile and on academic achievements at 9 years of age using a large-scale prospective paradigm. STUDY DESIGN: We followed up 123 infants diagnosed with late-onset intrauterine growth restriction yearly for 9 years. They were matched with 63 children for gestation age and multiple socioeconomic factors and evaluated by an extensive neuropsychological battery to assess intelligence quotient, academic achievements, learning and memory, visuomotor skills, visuospatial integration, attention, language, executive functions, and creativity. RESULTS: Children with intrauterine growth restriction had lower intelligence quotient and more frequent neuropsychological difficulties. Difficulties in executive functioning, inflexibility-creativity, and language, indicative of frontal lobe dysfunction, were typically affected by intrauterine growth restriction and were rarely identified in the control group. Learning difficulties accompanied by lower academic achievements were more prevalent in the intrauterine growth restriction group, particularly when anthropometric catch-up was incomplete. CONCLUSIONS: The longitudinal findings reaffirm that functional coherence depends on preestablished structural growth and reorganization of the central nervous system. The neuropsychological profile at 9 years of age indicates that late-onset intrauterine growth restriction compromises frontal network functioning.

Attention↗

Cognitive functioning after medial frontal lobe damage including the anterior cingulate cortex: a preliminary investigation.

Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was compared with age and education matched healthy controls. Both patients showed intact intellectual, memory, and language abilities. No clear-cut abnormalities were noted in visuoperceptual functions. Speed of information processing was mildly reduced only in Patient 2 (bilateral ACC lesion). The patients demonstrated weak or impaired performance only on selective executive function tests. Performance on anterior attention tasks was satisfactory. We tentatively suggest that our findings are inconsistent with anterior attention theories of ACC function based on neuroimaging findings. We propose that the data may imply that the ACC does not have a central role in cognition. We speculate that our findings may be compatible with the view that the ACC integrates cognitive processing with autonomic functioning to guide behaviour.

Adult↗

Cholinergic treatment of amnesia following basal forebrain lesion due to aneurysm rupture--an open-label pilot study.

Impairments of memory are often found after rupture and repair of aneurysms leading to a basal forebrain lesion. This open study investigated whether cholinergic substitution therapy may be a treatment option. The effect of donepezil, a cholinesterase inhibitor on memory functions was tested in an open-label, exploratory study in 11 patients with a chronic amnestic syndrome from a ruptured and repaired aneurysm of the anterior communicating artery (seven patients), the anterior cerebral (two) or the pericallosal artery (two). Mean time since onset was 75.4 months. Memory was evaluated at baseline and consecutively after 4 weeks of 5 mg donepezil daily, 8 weeks of 10 mg donepezil, and 4 weeks after drug discontinuation. Memory functions were assessed using the California Verbal Learning Test and compared with a matched group of normal, untreated controls. Tests of attention and of executive functions were also administered. Donepezil was well tolerated. Strong group effects were found at baseline and at all follow-up measurements showing profound impairments of memory functions in the patient group. Within patient statistics showed significant improvements of short and long delay free recall scores during the treatment period, both with 5 and 10 mg donepezil daily, whereas attentional and executive functions improved only non-significantly. Memory functions decreased after drug discontinuation. Repeated test administration in the control group also showed an increase of memory scores which was minor when compared with the performance change in the patient group. Donepezil may improve episodic memory functions in patients suffering from a chronic amnestic syndrome caused by rupture and repair of aneurysms of the anterior communicating, the anterior cerebral or the pericallosal artery. Future doubled-blind, placebo-controlled trials are warranted to confirm these findings.

Adult↗

The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers.

RATIONALE: Corticosteroids are elevated in certain neuropsychiatric disorders and this may contribute to the neuropsychological impairments reported in these disorders. OBJECTIVE: To examine the effects of hydrocortisone on learning, memory and executive function. METHODS: Hydrocortisone 20 mg was administered twice daily for 10 days to normal male volunteers in a randomized, placebo control, crossover, within-subject design. Learning, memory and executive function were measured using selected subtests from the Cambridge Neuropsychological Test Automated Battery. RESULTS: Hydrocortisone caused impairments of visuo-spatial memory. These included increased within search errors and impaired use of strategies on the spatial working memory subtest. In addition, administration of hydrocortisone was associated with more errors in the paired associate learning subtest, although no effect was found on the Tower of London. Hydrocortisone speeded response latencies in certain tests (pattern and spatial recognition memory). CONCLUSION: These results indicate that chronic administration of hydrocortisone leads to deficits in certain tests of cognitive function sensitive to frontal lobe dysfunction and may contribute to the cognitive impairment reported in certain neuropsychiatric disorders.

Adult↗

Executive deficits in chronic PTSD related to political violence.

UNLABELLED: Twenty-two subjects with chronic PTSD were compared to 23 subjects with no diagnoses (NPD) on tests of executive functioning (EF) that are assumed to have clinical significance after exposure to political violence. METHOD: The three cognitive components of EF, intentionality, inhibition and executive memory [Burgess, P. W., Alderman, N., Evans, J., Emslie, H., Wilson, B. A. (1998). The ecological validity of tests of executive function. Journal of the International Neuropsychological Society, 4, 547-58], were measured using the Tower of London, Stroop Color-Word Test and Wisconsin Card Sorting Test (WCST), respectively. RESULTS: The PTSD group was impaired on tasks measuring automatic processing and executive memory. Executive memory problems were related to elevated posttraumatic symptoms, but the executive components intentionality and inhibition did not differentiate the groups. Arousal and intrusive symptoms had no impact on intentionality. CONCLUSION: Posttraumatic symptoms are related to automatic processing problems and impairment in executive memory. Observed dysfunctions in mental flexibility could have a negative impact on the cognitive processing of traumatic memory, thus preventing from recovery.

Adolescent↗

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.

Adolescent↗

Are the cognitive deficits associated with impaired insight in schizophrenia specific to executive task performance?

Although impaired insight in schizophrenia has been associated with deficits in executive task performance, the relationship remains unclear. We aimed to clarify this relationship by fractionating executive functioning into the theoretically derived functions of inhibition, working memory, set shifting, and sustained attention. We compared the performance of patients showing impaired insight, patients showing good insight, and a matched control group on measures of each of these executive functions, along with measures of current cognitive functioning and memory. We found that while patients with impaired insight performed significantly below those with good insight on our working memory task, they also performed poorly on measures of general cognitive functioning and memory. We conclude that while impaired insight does appear to be associated with executive deficits, this association may not be specific but may instead relate to cognitive deficits more generally.

Adult↗

Neuropsychological changes in a prospectively followed cohort of homosexual and bisexual men with and without HIV infection.

We evaluated neuropsychological test performance of 168 homosexual and bisexual men with and without human immunodeficiency virus (HIV) infection (113 HIV+ subjects and 55 HIV- controls) over 4.5 years of semiannual follow-up. Analyses of the longitudinal data were performed by applying generalized estimating equations (GEEs) to regression analyses with repeated measures. Compared with the HIV- men, the HIV+ subjects performed more poorly on memory testing. Performance on all tests tended to improve over time, but this improvement was attenuated or eliminated in the HIV+ group for tests of language and attention. Within the HIV+ subjects, improvement over time in tests of memory, executive function, language, and attention was attenuated or eliminated in patients with lower CD4 levels; more advanced HIV disease was associated with poorer memory and executive function and with attenuated or reduced learning effects for memory, motor speed, and language tests. Clinically significant neurologic findings were associated with worse memory and orientation and with attenuated or reversed learning effects for memory, language, and attention tests. There were 33 deaths in the HIV+ group. In the men who died, there was more rapid decline in executive, language, and attentional test performance. These observations remained significant after controlling for HIV disease severity. We conclude that HIV infecting the CNS results in progressive cognitive change that is closely associated with neurologic findings. In addition, our findings suggest a relation between more rapid cognitive progression and death.

Adult↗

Heavy alcohol consumption in individuals with HIV infection: effects on neuropsychological performance.

Higher rates of alcohol use have been reported in HIV+ individuals compared to the general population. Both heavy alcohol use and HIV infection are associated with increased risk of neuropsychological (NP) impairment. We examined effects of heavy active alcohol use and HIV on NP functioning in a large sample of community-residing HIV+ individuals and HIV- controls. The four main study groups included 72 HIV- light/non-drinkers, 70 HIV- heavy drinkers (>100 drinks per month), 70 HIV+ light/non-drinkers, and 56 HIV+ heavy drinkers. The heavy drinking group was further subdivided to assess effects of the heaviest levels of active alcohol use (>6 drinks per day) on NP functioning. A comprehensive NP battery was administered. Multivariate analysis of covariance was employed to examine the effect of HIV and alcohol on NP functioning after adjusting for group differences in age and estimated premorbid verbal intellectual functioning. The analyses identified main effects of heavy drinking and HIV on NP function, with greatest effects involving the contrast of HIV+ heavy drinkers and the HIV- light drinkers. Synergistic effects of heaviest current drinking and HIV infection were identified in analyses of motor and visuomotor speed. Supplementary analyses also revealed better NP function in the HIV+ group with antiretroviral treatment (ART) and lower level of viral burden, a finding that was consistent across levels of alcohol consumption. Finally, heavy alcohol use and executive functioning difficulties were associated with lower levels of self-reported medication adherence in the HIV+ group. The findings suggest that active heavy alcohol use and HIV infection have additive adverse effects on NP function, that they may show synergistic effects in circumstances of very heavy active alcohol use, and that heavy drinking and executive functioning may mediate health-related behaviors in HIV disease.

Adult↗

Impairment in event sequencing in disorganised and non-disorganised patients with schizophrenia.

It has been suggested that thought disorder in schizophrenia is associated with impaired executive functions and with a defective understanding of others' behaviour. Action sequence knowledge processing and goal detection are considered as crucial components of executive functioning. Here, we used a picture-sequencing task to assess the ability of schizophrenic patients (n = 40) with and without disorganisation symptoms to arrange different types of action sequence representations. Disorganisation symptoms appear to be associated with a general sequencing impairment, while patients without disorganisation symptoms displayed difficulties in ordering sequences requiring subjects to infer mental states in story characters along with a relatively preserved performance in correctly arranging mechanical or behavioural event sequences. These results reveal that only schizophrenic patients without disorganisation symptoms show a selective deficit in mentalising abilities whereas disorganisation symptoms are associated with a more severe event sequencing impairment probably reflecting basic failures of inferential reasoning.

Adult↗

Is the phonological loop responsible for intelligence-related differences in forward digit span?

Children with mild mental retardation were compared with CA-matched and verbal-age-matched children without mental retardation on a forward digit span task. Forward digit span is typically used as a measure of the phonological loop (Baddeley, 1986). We hypothesized that intelligence-related differences in forward digit span are largely due to central executive functioning rather than phonological loop functioning. Results showed that the highly significant group difference in forward digit span was reduced to nonsignificance when a measure of central executive functioning was covaried out.

Attention↗

Age-related differences and complexity of ongoing activities in time- and event-based prospective memory.

Aging is presumed to disrupt self-initiated processing, and a time-based prospective memory task (i.e., action to be performed at a particular time) entails more self-initiated activities than an event-based prospective memory task (i.e., action to be performed to a critical event). Accordingly, older participants are predicted to be particularly bad in a time-based prospective memory task. However, the prediction is not always confirmed. Self-initiated activities entail central executive functioning. We therefore predicted the age deficit to emerge more clearly when the performance on the ongoing task also involved more central executive functioning. Time-based prospective memory among older adults collapsed when the complexity of the ongoing task increased. However, an age deficit was also obtained when the pacing of the event-based prospective memory task was high because of the general slowing of functioning by older adults.

Adolescent↗