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PubMed2005

One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia.

Neurocognitive deficits in schizophrenia can reach 1 to 2 standard deviations below healthy controls. The comparative effect of typical and atypical antipsychotic medications on neurocognition is controversial, and based primarily on studies with small samples and large doses of typical comparator medications. The present study assessed neurocognitive efficacy. It was hypothesized that olanzapine treatment would improve neurocognitive deficits to a greater degree than either risperidone or haloperidol treatment. This was a double-blind, randomized, controlled, parallel study with neurocognition assessed at baseline, and 8, 24, and 52 weeks. Per protocol, the haloperidol arm was discontinued. Four hundred and fourteen inpatients or outpatients with schizophrenia and schizoaffective disorder were treated with oral olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Individual domains (executive function, learning and memory, processing speed, attention/vigilance, verbal working memory, verbal fluency, motor function, and visuospatial ability) were transformed into composite scores and compared between treatment groups. At the 52-week endpoint, neurocognition significantly improved in each group (p < 0.01 for olanzapine and risperidone, p = 0.04 for haloperidol), with no significant differences between groups. Olanzapine- and risperidone-treated patients significantly (p < 0.05) improved on domains of executive function, learning/memory, processing speed, attention/vigilance, verbal working memory, and motor functions. Additionally, risperidone-treated patients improved on domains of visuospatial memory. Haloperidol-treated patients improved only on domains of learning/memory. However, patients able to remain in treatment for the entire 52 weeks benefited more from olanzapine or risperidone treatment than haloperidol treatment.

Adolescent↗

PubMed2005

Final transitions: family caregiving at the end of life.

BACKGROUND: This study aimed to understand how caregivers make the transition to end-stage caregiving and to illuminate its unique aspects using a stress process model. METHODS: Qualitative in-depth interviews were conducted with 74 caregivers of a family member who had been receiving hospice care for at least 2 weeks. Interviews were tape recorded, transcribed, and coded for emergent themes using constant comparative analysis. RESULTS: End-stage caregiving was characterized in the sample as (1) comprehension of terminality (the interrelationship of information, physical and cognitive decline, and personality change and role losses), (2) near-acute care, (3) executive functions, and (4) final decision making. The comprehension of terminality emerged from three interrelated experiences: receiving and assimilating concrete information about the illness, observing the progression of the disease, and observing the personality change and role loss. The primary stressors (unique end-stage caregiving tasks) were providing near-acute care, assuming an executive function, and beginning and final decision making. The secondary stressors were family role conflict, work conflict, and financial strain. Resources, such as intrinsic and extrinsic religious and faith practices and social support, were identified. Negative outcomes included intense emotional responses, and positive outcomes included heightened development of meaning making. CONCLUSION: The findings suggest that palliative care professionals have important opportunities to provide information and support to family caregivers during the final stages of the patient's terminal illness.

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PubMed2006

Sensorimotor gating deficits in adults with autism.

BACKGROUND: Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is impaired in a family of neuropsychiatric disorders characterized by abnormalities of inhibitory function. Adults with autistic disorder (AD) exhibit clinical features of inhibitory deficits, such as restrictive and repetitive behaviors, that may be explained by deficits in sensorimotor gating. METHODS: Acoustic startle reactivity, habituation, and PPI (30-, 60-, 120-msec interstimulus intervals) were assessed in 14 adult men diagnosed with AD and 16 typically developing normal comparison (NC) participants. All participants were administered measures of intelligence and frontal-executive functioning. RESULTS: Adults with AD exhibited significantly less PPI in the 60-msec condition than NC participants, which was correlated with increased ratings of restricted and repetitive behaviors. The groups did not differ on measures of startle amplitude or overall habituation. There was, however, a significant group-by-block habituation effect. Furthermore, PPI was not related to intelligence but was moderately associated with performance on a measure of frontal-executive functioning. CONCLUSIONS: Adults with AD have sensorimotor gating deficits similar to other neurodevelopmental disorders, implicating a failure of normal inhibitory regulation of sensory, motor, and attentional mechanisms. Thus, PPI deficits may be indirectly linked to one of the hallmark features of AD.

Acoustic Stimulation↗

PubMed2005

Corpus callosum size correlates with asymmetric performance on a dichotic listening task in healthy aging but not in Alzheimer's disease.

Alzheimer's disease (AD) involves not only gray matter but also white matter pathology, as reflected by atrophy of the corpus callosum (CC). Since decreased CC size may indicate reduced functional interhemispheric connectivity, differences in callosal size may have cognitive consequences that may become specifically apparent in neuropsychological tasks that tap hemispheric laterality. In the present study, we examined callosal functioning with a dichotic listening task in 25 Alzheimer patients, 20 healthy elderly and 20 healthy elderly with subjective memory complaints. We found decreased performance, increased ear asymmetry, and decreased callosal size in the AD group compared to healthy elderly. As expected, in the healthy elderly, we found significant negative correlations between ear asymmetry and callosal size, specifically in the anterior and posterior callosal subareas. While the association with the posterior subareas (isthmus and splenium) points at involvement of temporal areas mediating language processing, the association with the anterior subarea (the rostrum and genu) points at involvement of frontal areas mediating attention and executive functions. Remarkably however, in contrast to the healthy elderly, callosal size was not related to ear asymmetry in the AD group. The absence of an association between callosal atrophy and ear asymmetry implies that other pathological processes, next to reduced callosal functioning, attribute to ear asymmetry in AD. Difficulties to attend specifically to the left ear during dichotic listening in some of the AD patients, points at decreased attention and executive functions and suggests that pathology of specifically the frontal areas is involved.

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PubMed2000

Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices.

Distinct domains of the prefrontal cortex in primates have a set of connections suggesting that they have different roles in cognition, memory, and emotion. Caudal lateral prefrontal areas (areas 8 and 46) receive projections from cortices representing early stages in visual or auditory processing, and from intraparietal and posterior cingulate areas associated with oculomotor guidance and attentional processes. Cortical input to areas 46 and 8 is complemented by projections from the thalamic multiform and parvicellular sectors of the mediodorsal nucleus associated with oculomotor functions and working memory. In contrast, caudal orbitofrontal areas receive diverse input from cortices representing late stages of processing within every unimodal sensory cortical system. In addition, orbitofrontal and caudal medial (limbic) prefrontal cortices receive robust projections from the amygdala, associated with emotional memory, and from medial temporal and thalamic structures associated with long-term memory. Prefrontal cortices are linked with motor control structures related to their specific roles in central executive functions. Caudal lateral prefrontal areas project to brainstem oculomotor structures, and are connected with premotor cortices effecting head, limb and body movements. In contrast, medial prefrontal and orbitofrontal limbic cortices project to hypothalamic visceromotor centers for the expression of emotions. Lateral, orbitofrontal, and medial prefrontal cortices are robustly interconnected, suggesting that they participate in concert in central executive functions. Prefrontal limbic cortices issue widespread projections through their deep layers and terminate in the upper layers of lateral (eulaminate) cortices, suggesting a predominant role in feedback communication. In contrast, when lateral prefrontal cortices communicate with limbic areas they issue projections from their upper layers and their axons terminate in the deep layers, suggesting a role in feedforward communication. Through their widespread connections, prefrontal limbic cortices may exercise a tonic influence on lateral prefrontal cortices, inextricably linking areas associated with cognitive and emotional processes. The integration of cognitive, mnemonic and emotional processes is likely to be disrupted in psychiatric and neurodegenerative diseases which preferentially affect limbic cortices and consequently disconnect major feedback pathways to the neuraxis.

Animals↗

PubMed2004

Patterns of memory impairment and perseverative behavior discriminate early Alzheimer's disease from subcortical vascular dementia.

Previous research suggests that the neuropsychological deficits in Alzheimer's disease (AD) are different from that of vascular dementia (VaD), especially with respect to memory, language and executive functions, but negative findings were reported. Our objective was to clarify the cognitive syndrome in AD and VaD in the early stage of these disorders. We investigated 45 patients with early AD, 23 patients with subcortical VaD and 35 normal controls. All subjects were assessed with neuropsychological battery designed to measure memory, language, praxis and executive functions. Patients with AD had significantly worse scores on Story Recall (p<0.02) and on all measures of the Free and Cued Selective Reminding Test (p<0.03 to 0.001) than did patients with VaD, as well as greater number of perseverations (p<0.02) on category fluency. Conversely, VaD patients had more perseverations (p<0.02) on the Modified Card Sorting Test. Despite the similar degree of overall cognitive deterioration, the findings show more impaired retrieval from long-term storage in AD than in VaD. Moreover, the data suggest that AD and subcortical VaD affect perseverative behavior in a different fashion. These results may be helpful in differentiating AD from VaD in the early stage of these disorders, when mental impairments are not pervasive yet.

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PubMed2002

Persistent cognitive deficits associated with lithium intoxication: a neuropsychological case description.

We present the case of a 51-year-old patient with an acute lithium intoxication associated with several cognitive deficits. During the acute phase of intoxication the patient displayed general psychomotor slowing, dysarthric speech, mood changes, and incoherent discourse. Neuropsychological assessment revealed ideomotor apraxia, profound deficits of visuospatial processing, an impairment of memory and of frontal-executive functions. Other cognitive abilities, such as orientation, spontaneous speech, comprehension, naming, reading, writing, and working memory remained intact. An electroencephalogram revealed diffuse slowing with rhythmic trains, whereas MRI showed no cerebral abnormality. Follow-up examinations at 4 and 14 weeks with lithium levels in the normal range showed substantial recovery of memory abilities and executive functions, whereas praxis and visuoperceptual functions remained impaired, despite the fact that lithium was immediately withdrawn after the intoxication became manifest. We conclude that lithium intoxication may be associated with variable behavioural and cognitive impairments, some of them potentially persistent. Different from other case studies our findings suggest that lithium intoxication may cause a combined, multifocal functional impairment of subcortical and cortical neural mechanisms in both hemispheres.

Antimanic Agents↗

PubMed2001

Acting nasty in the face of failure? Longitudinal observations of "hard-to-manage" children playing a rigged competitive game with a friend.

Peer problems are almost universal among children with disruptive behavior disorders, and have been linked to social information processing deficits that lead to heightened threat responses. This 2-year longitudinal study uses direct observations to examine the real-life significance of this finding. Forty "hard-to-manage" children and 40 typically developing control children were filmed at ages 5 and 7 playing a rigged competitive game in which they experienced a clear threat of losing. Group differences in negative behavior (hard-to-manage > controls) were stable over time and independent of verbal ability. Predictors of individual differences in negative behavior were also examined. Previous studies with this sample have shown that at 4 years of age, the hard-to-manage children displayed elevated frequencies of violent pretend play, coupled with poor performance on tests of executive function and theory of mind. In this study, 4-year-olds whose pretend play indicated a preoccupation with violence were more likely to respond negatively to the threat of losing a competitive game at age 5 and at age 7. Four-year-olds who performed poorly on tests of theory of mind and executive function showed higher rates of negative behavior at age 5 but not age 7. These findings highlight just a few of the multiple paths leading to peer problems among children with disruptive behavior problems.

Affect↗

PubMed2005

Selective cognitive deficits in obsessive-compulsive disorder compared to panic disorder with agoraphobia.

OBJECTIVE: Visual-spatial and executive functions deficits have been reported in obsessive-compulsive disorder (OCD). We investigated their specificity comparing cognitive function in OCD, panic disorder with agoraphobia (PD/A) and controls by a comprehensive neuropsychological battery. METHOD: Fifty-five subjects (25 OCD, 15 PD/A, 15 controls) without current depressive episode underwent structured clinical interview for DSM-IV, Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale. Neuropsychological battery assessed: executive functions, visual discrimination, spatial memory and learning, verbal memory, general intellectual functioning. RESULTS: OCD showed controlled fluency, visual-spatial construction, learning and memory deficits; PD/A spatial learning impairment. OCD was discriminated from PD/A and controls by three tests scores, predicting group membership for 76.4% of the cases. CONCLUSION: Visual-constructive and controlled fluency deficits seem specific in OCD, while the spatial learning deficit, shared with PD patients, may not be disorder-specific, but anxiety-related. Results support the proposed ventral frontal-striatal circuit involvement in OCD.

Adolescent↗

PubMedDate not supplied

Neuropsychological findings in hyperthyroid patients.

AIM: to evaluate attention, concentration, memory changes and executive function inpatients with hyperthyroidism compared with normal thyroid function patients. METHODS: a cross sectional study was conducted in 21 patients (14F, 7M) with symptoms of sweating, sleep disturbance, fine tremor, headache, palpitation, nervousness, forgetfulness and diarrhea. Neurological examination found that 2 patients had proximal paresis and periodic paralysis. Their thyroid functions (FT4 and TSHS) were done, 13 patients were hyperthyroid, 2 patients were subclinical hyperthyroid and 6 patients were euthyroid. Neuropsychological tests such as: Mini Mental State Examination (MMSE), Trail Making Test (TMT) A and B, Continuous Performance Test (CPT), Vigilance Complex Task (VCT), Digit Forward and Backward Repetition (DFR, DBR) were performed in all of those patients. The mean age of sample was 47,3 +/- 8,45 years old and all of them had minimal 6 years education background, no history of cerebro vascular disease, brain injury or tumour or infection, epilepsy, cerebral degeneration, and taking neuroleptics or antidepressants. RESULTS: using the Kendall correlation coefficients showed that FT4 had negative correlation with VCT, CPT, DFR, DBR and positive correlation with TMT A (time) and TMT B (time and error). Study T-test showed that high level of thyroid function had significant difference in TMT A (time), TMT B (time), DBR, DFR, VCT, CPT. Fischer exact gave statistically significant in VCT and fine tremor in hyperthyroid patients (RR VCT 5.60, 95% CI 0.93-33.68, RR fine tremor 0.50, 95% CI 0.28-0.88). CONCLUSION: hyperthyroid patients had significant decrease on attention, concentration, verbal memory and executive function (working memory) compared with euthyroid patients.

Adult↗

PubMed2003

Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.

BACKGROUND: Newer antipsychotic medications have been reported to enhance cognitive functioning in schizophrenia. Head to head studies with double-blind methods are still relatively few in number. OBJECTIVES: To compare the relative cognitive enhancing effects of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder. PROCEDURES: In this 6-week, multicenter, double-blind, parallel-designed trial, patients were randomized to ziprasidone or olanzapine. No patient who had ever received a complete treatment trial with either of these medications previously was entered into the study. Cognitive testing measuring attention, motor speed, memory, executive functioning, and verbal skills were performed on all patients at baseline and endpoint. RESULTS: Treatment with either ziprasidone or olanzapine was associated with statistically significant improvements from baseline in attention, memory, working memory, motor speed, and executive functions. Treatment with olanzapine was also associated with a statistically significant improvement in verbal fluency. No statistically significant differences between these medications were found in the magnitude of improvement from baseline on any of the cognitive measures (other than verbal fluency in an exploratory analysis). Observed changes were not associated with changes in clinical symptoms measured using the PANSS or changes in movement disorders. CONCLUSIONS: During 6 weeks of treatment, ziprasidone and olanzapine demonstrated substantial and comparable cognitive-enhancing effects relative to previous treatment. These effects were noted in all aspects of cognitive functioning previously proven to predict functional outcome in schizophrenia. No overall differences were detected between the medications in terms of the extent of cognitive enhancement.

Adult↗

PubMed2005

Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing.

CONTEXT: Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear. OBJECTIVE: We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging. DESIGN: Cross-sectional case-control design. SETTING: Community; outpatient clinic. Patients Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning. MAIN OUTCOME MEASURES: Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d' (a measure based on the hit rate and the false-alarm rate). RESULTS: The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group. CONCLUSIONS: Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals.

Adolescent↗

PubMed2004

Clipping versus coiling: neuropsychological follow up after aneurysmal subarachnoid haemorrhage (SAH).

Patients treated with microsurgical clipping of ruptured intracranial aneurysms often suffer from neuropsychological deficits in spite of a good neurological outcome. The purpose of this study was to explore if the deficits are related to the type of therapy. Two groups of 16 patients each suffering from aneurysmal SAH, matched for sex, age, aneurysm-site and Hunt and Hess score, and 16 control subjects were examined with a battery of neuropsychological tests including memory, attention, and executive function. Depression, mood, and quality of life were also assessed. One patient group had been treated with surgical clipping, the other with endovascular coiling. Both patient groups showed deficits in verbal and visual memory. Clipped patients were slightly more impaired than coiled patients, especially on measures of affect and on a self-assessment measure of executive function. The pattern of results suggests that the neuropsychological outcome after aneurysmal SAH is affected by both the severity of the bleeding and the type of therapy.

Affect↗

PubMed2005

Prolonged cognitive dysfunction in survivors of critical illness.

A prospective study using neuropsychological testing explored cognitive performance, and specifically executive function, in survivors of critical illness during the first year of recovery. Fifty-one patients who had survived 3 days or more in the intensive care unit were studied approximately 3 months after discharge; 45 of them were studied again 6 months later. General health was assessed using the Short-Form 36. Cognitive and executive functions were measured using Raven's Progressive Matrices, the Hayling Sentence completion test and the Six-Element Test. Three months after discharge from intensive care, all eight domains of Short-Form 36 were impaired among survivors; by 9 months, four of the eight domains showed significant improvement. At 3 months, 35% of patients scored at or below a level equivalent to the lowest performing 5% of a normal population (i.e. the fifth percentile) on two or more tests of cognitive function; by 9 months only 4% of patients were impaired to this extent. Although cognitive performance improved with time, it remained below normal.

Adult↗

PubMed1999

Procedural learning is impaired in patients with prefrontal lesions.

OBJECTIVES: To 1) determine the effect of prefrontal cortex lesions on procedural learning (PL), measured by a serial reaction-time task (SRTT); 2) confirm whether visuomotor PL is lateralized to one hemisphere; and 3) clarify the relation between visuomotor sequence learning and verbal sequence learning, working memory, and executive functions. BACKGROUND: Previous cognitive neuroscience research has implicated the prefrontal cortex in visuomotor PL but there is a lack of studies examining patients with prefrontal cortex lesions. METHODS: We studied 22 patients with strictly unilateral prefrontal cortex lesions (traumatic, ischemic, hemorrhagic, or tumors) and 52 cognitively intact controls matched for age, sex, and educational level. We administered to subjects long (10-item sequence) and short (4-item sequence) versions of the SRTT. With the long version, each hand was evaluated separately. Learning was indicated by the shortening of response times (RT) and decrease in errors across the sequential blocks and, most importantly, the rebound increase in RTs and errors when comparing the last sequence block with the next random block. Frontal lobe functions and verbal sequence learning were also assessed. RESULTS: Patients with unilateral prefrontal cortex lesions show PL impairment that involves both hands, although more errors were observed when the hand contralateral to the lesion was performing. Only those patients whose lesions were >2 cm in diameter were impaired. Neuropsychologic evaluation indicated impaired verbal sequence learning and executive function deficits. Patients with poorer working memory and verbal sequence learning were also more impaired in visuomotor sequence learning. CONCLUSIONS: The prefrontal cortex has a role in PL and is part of the neural circuit that mediates this type of learning.

Adult↗

PubMed1996

Biological correlates of learning and attention: what is relevant to learning disability and attention-deficit hyperactivity disorder?

Advances in the related fields of cognitive neuroscience and neuropsychology offer intriguing reformulations of the clinical entities of attention-deficit hyperactivity disorder (ADHD) and learning disabilities (LD). The definition of such terms as attention and learning used in cognitive neuroscience differ from their use in clinical practice and emphasize such processes as intention, working memory, and executive function. Research suggests that neither attention nor long-term memory are the critical cognitive correlates of ADHD or LD. Rather, encoding processes, particularly working memory, are identified as deficiencies for children with these conditions. Furthermore, intention and inhibition appear to be particularly impaired in children with ADHD, who exhibit broader deficits in so-called executive function. Findings from cognitive neuroscience offer explanations of the neuroanatomical and neurophysiological underpinnings of learning problems and the frequent comorbidity of LD and ADHD.

Attention↗

PubMed2006

Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed.

BACKGROUND: A number of studies have examined clinical factors linked to worse neuropsychological performance in late life depression (LLD). To understand the influence of LLD on cognition, it is important to determine if deficits in a number of cognitive domains are relatively independent, or mediated by depression- related deficits in a basic domain such as processing speed. METHODS: Patients who met DSM-IV criteria for major depression (n = 155) were administered a comprehensive neuropsychological battery of tasks grouped into episodic memory, language, working memory, executive function, and processing speed domains. Multiple regression analyses were conducted to determine contributions of predictor variables to cognitive domains. RESULTS: Age, depression severity, education, race and vascular risk factors all made significant and independent contributions to one or more domains of cognitive function, with all five making independent contributions to processing speed. Age of onset made no independent contribution, after accounting for age and vascular risk factors. Of the five cognitive domains investigated, changes in processing speed were found to most fully mediate the influence of predictor variables on all other cognitive domains. CONCLUSIONS: While slowed processing speed appears to be the most core cognitive deficit in LLD, it was closely followed by executive function as a core cognitive deficit. Future research is needed to help clarify mechanisms leading to LLD- related changes in processing speed, including the potential role of white matter abnormalities.

Activities of Daily Living↗

PubMed2004

Deficits in decoding emotional facial expressions in Parkinson's disease.

INTRODUCTION: The basal ganglia have numerous connections not only with the motor cortex but also with the prefrontal and limbic cortical areas. Therefore, basal ganglia lesions can disturb motor function but also cognitive function and emotion processing. The aim of the present study was to assess the consequences of Parkinson's disease (PD) on ability to decode emotional facial expressions (EFEs)-a method commonly used to investigate non-verbal emotion processing. METHODS: Eighteen PD patients participated in the study, together with 18 healthy subjects strictly matched with respect to age, education and sex. The patients were early in the course of the disease and had not yet received any antiparkinsonian treatment. Decoding of EFEs was assessed using a standardized, quantitative task where the expressions were of moderate intensity, i.e. quite similar to those experienced in everyday life. A set of tests also assessed executive function. Visuospatial perception, depression and anxiety were measured. RESULTS: Early in the course of the disease, untreated PD patients were significantly impaired in decoding EFEs, as well as in executive function. The deficits were significantly interrelated, although neither was significantly related to severity of the motor symptoms. Visuospatial perception was not impaired, and the patients' impairment was related neither to their depression nor to their anxiety score. The PD patients' impairment in decoding EFEs was related to a systematic response bias. CONCLUSION: Early in the course of PD, non-verbal emotional information processing is disturbed. This suggests that in PD, nigrostriatal dopaminergic depletion leads not only to motor and cognitive disturbances but also to emotional information processing deficits. The observed correlation pattern does not enable adoption of a clear-cut position in the debate over totally or partially segregated functional organization of the basal ganglia circuits.

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