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PubMed2000

Information processing and attentional dysfunctions as vulnerability indicators in schizophrenia spectrum disorders.

The schizotypal personality disorder is believed to be part of the schizophrenic spectrum of disorders including schizophrenic patients as well as some of their seemingly unaffected relatives with discreet symptoms. Spectrum-individuals are characterised by a genetic vulnerability for schizophrenia. The vulnerability is connected with neurocognitive deficits independent of clinical state. Some cognitive dysfunctions are unspecific and probably related to non-genetic brain damage. A consistent finding has, however, been poor performance in tasks involving information processing and attention. The findings point to the existence of specific sensory-perceptual deficits or a general attentional dysfunction. Identification of cognitive disturbances characteristic not only of schizophrenics, but also of schizotypal disordered and their relatives in the boundaries of schizophrenia, is relevant in order better to understand the pathogenetic mechanisms and treatment of schizophrenia. In the present review clinical data are analysed based on models of vulnerability and information processing with reference to a characterisation of the neuro-integrative deficits that form the core abnormalities of the spectrum.

Attention↗

PubMed1991

Experience with rehabilitation in the acquired immunodeficiency syndrome.

Patients with the acquired immunodeficiency syndrome (AIDS) represent a novel referral population for rehabilitation services. Limited information about the rehabilitation needs of individuals with human immunodeficiency virus infection is available. We reviewed 51 consecutive patients with AIDS referred to a rehabilitation consult service. Common problems encountered included generalized deconditioning (27%) and neurologic dysfunction (45%). Neurologic presentations were diverse and included hemiparesis, diffuse cognitive dysfunction and dementia, myelopathy, myopathy and peripheral neuropathy. Other patients were referred for wound care as well as the management of the local effects of Kaposi's sarcoma, various musculoskeletal syndromes and new onset blindness. Problems identified included impaired mobility (76%), difficulty with self-care (57%), impaired cognition (29%) and uncontrolled pain (37%). Among the rehabilitation interventions utilized were therapeutic exercise (73%), gait aids (45%), bathroom and safety equipment (45%), orthotics (29%), vocational counseling (4%), pain management (29%) and whirlpool treatments (10%). Five patients were too ill or refused treatment. We conclude that AIDS patients referred for rehabilitation have a wide variety of physical deficits, demonstrate a considerable degree of functional impairment and may require multiple rehabilitation interventions.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Effect of long-term oxygen therapy on cognitive and neurological dysfunction in chronic obstructive pulmonary disease.

The aim of this study was to assess effect of long-term oxygen therapy (LTOT) on the function of central and autonomic nervous system in patients with hypoxaemic chronic obstructive pulmonary disease (COPD). A battery of neuropsychological tests was used together with the Short Test of Mental Status in addition to transcranial Doppler ultrasonography, and five cardiovascular tests as well as a questionnaire on autonomic function. Ten COPD patients, 4 males and 6 females, with a mean age of 65.9 +/- 7.3 (SD) years, were studied at the beginning and after 3 months of LTOT. At start PaO2 was 6.7 +/- 1.1 kPa without oxygen and 9.9 +/- 1.5 kPa after 3 months with oxygen. Our results demonstrate that neuropsychological function, cerebral blood flow velocity and autonomic function were positively influenced after 3 months of LTOT although the changes did not reach statistical significance. The COPD patients were cognitively impaired as compared to age-matched healthy controls. Our findings were consistent with the previous notion of improvement of hypoxic cognitive dysfunction by LTOT.

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PubMed1998

Selective attention in schizophrenia: relationship to verbal working memory.

In previous work using the Stroop task to examine cognitive function in schizophrenia, we have suggested that reaction time (RT) facilitation and error interference should be more sensitive measures of cognitive function than RT interference. We examined this hypothesis in 36 DSM-IV schizophrenia and schizoaffective patients, who performed both the Stroop and the Speaking Span, a measure of verbal working memory. The results supported our hypotheses, demonstrating that RT facilitation and error interference were associated more strongly with working memory performance than RT interference. The robust correlations between these measures of selective attention and Speaking Span performance has implications for understanding the nature and selectivity of cognitive dysfunction in schizophrenia. We present several different hypotheses that may explain this relationship, including: (1) a generalized deficit; (2) a common cognitive disturbance; and (3) a common neurobiological dysfunction.

Adult↗

PubMed1987

Neurocognitive impairment in alcoholics: review and comparison with cognitive impairment due to AIDS.

This review indicates that cognitive dysfunction and dementia, specifically caused by chronic alcohol use, consist of subtle changes in cognition which are easily missed and/or forgotten. The nature of the dysfunction and specific neuropsychiatric and neurodiagnostic tests will be reviewed. There are important treatment implications regarding these subtle changes in mental function. Treatment implications will also be summarized. Finally, a comparison will be made between the cognitive impairment experience by patients with Acquired Immune Deficiency Syndrome from that experienced by alcoholics.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Mini mental state examination in geriatric stroke patients. Validity, differences between subgroups of patients, and relationships to somatic and mental variables.

To study the validity of the Mini Mental State Examination (MMSE) in geriatric stroke patients, 116 patients were tested 2-8 weeks and 6 months post-stroke. A neuropsychological test battery consisting of five tests measuring memory, calculation and spatial ability was used for validation. Motor activity, depression, aphasia and activities of daily living were assessed. Confusion in the acute stage, Barthel Index, depression scores, level of motor activity, and most of the neuropsychological tests correlated to the MMSE. Logistic regression showed 4 independent variables which could predict the MMSE scores. A factor analysis showed 3 factors which could explain 53% of the variance. The sensitivity for detecting dementia was 56%, and increased to 68% if patients with isolated spatial dysfunction were excluded. The MMSE had acceptable validity in detecting cognitive dysfunction early poststroke in this old patient population.

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PubMed2005

Brain perfusion SPECT in patients with mild cognitive impairment and Alzheimer's disease: comparison of a semiquantitative and a visual evaluation.

Due to the increasing importance of early recognition and differential diagnosis of dementias, cerebral perfusion scans using "single photon emission computed tomography" (SPECT) are increasingly integrated into the examination routine. The goal of this study was to check the diagnostic validity of SPECT scans of MCI- and DAT-patients, two subgroups out of 369 persons with etiologically unclear cognitive dysfunction, which underwent an assessment program for probable dementia including cognitive testing, cranial computed tomography, ultrasound, routine laboratory testing including vascular risk factors. After exclusion of patients with no or other forms of dementia we analyzed SPECT data of patients with mild cognitive impairment (MCI; n = 85) and dementia of the Alzheimer type (DAT; n = 78) in comparison with a healthy control group (n = 34).Visual assessment as well as a manual "regions of interest" (ROI) regionalization of the cortex were performed, whereby a ROI/cerebellum ratio was calculated as a semi-quantitative value. Association cortex areas were assessed regarding frontal, temporal, and parietal lobes of both hemispheres. When comparing the ratios of patients with DAT and controls, we found a statistically significant reduction of the cerebral perfusion in all measured cortex areas (p < 0.001). The comparison of patients with MCI with the selected control group also established a statistically significant difference in the cerebral perfusion for the evaluated cortex areas with the exception of the left hemispheric frontal and parietal cortex.A considerable number of the MCI patients showed an MMSE-score within the normal range, but with regard to the perfusion in the right hemispheric association cortex these patients also could be distinguished unambiguously from controls. Sensitivity levels found by visual assessment were at least as high as those found by the ROI method (pathological assessment: visual 49.4% vs. ROI 47.1% for MCI; visual 75.6% vs. ROI 73.1% for DAT). High experienced visual assessment of cerebral perfusion scans using SPECT provides an useful additional tool in diagnosis of cognitive impairment. The used semiquantitative ROI-method is nearly equivalent and does not depend on the experience of the investigator.

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PubMed2006

Neuropsychologic aspects of post-traumatic headache and chronic daily headache.

The management of patients with chronic refractory head pain remains a treatment challenge. Treatment focus should be multidisciplinary as patients evolve into a deteriorated status with psychologic, social, vocational, and cognitive dysfunction. The neuropsychologist will gather premorbid and comorbid information, assess cognitive functioning, and be involved in every behavioral medicine and treatment decision. The patient with post-traumatic head pain copes with head injury sequelae. Issues related to worker's compensation, insurance, disability decisions, and litigation are intrinsic to these patient groups.

Craniocerebral Trauma↗

PubMed2004

Nicotine effects on brain function and functional connectivity in schizophrenia.

BACKGROUND: Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. METHODS: Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. RESULTS: During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. CONCLUSIONS: In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Adult↗

PubMed2006

Cognitive disturbances in old dogs suffering from the canine counterpart of Alzheimer's disease.

In geriatric dogs, Alzheimer-like behavior is frequently observed. This behavior has been classified by several authors using questionnaires and a correlation has been described between cognitive dysfunctions and Alzheimer-like pathology. In the present study, cognitive performance was correlated with brain pathology for 30 dogs of varying ages. Within these animals, two age-matched groups of old dogs with and without behavioral changes were compared. The behavioral changes were analyzed and scored with questionnaires and necropsy was performed to rule out any other cause for changed behavior. Measurements, (immuno)-histochemical staining and fluorescence microscopy were used to detect cortex atrophy, amyloid, rest-products of oxidative damage, demyelination and accumulations of macrophages in the brains of these dogs. Spearman rank correlation coefficients (r) were calculated and adjusted according to Bonferonni. In the whole group (young to very old dogs), the age of the animal showed a significant correlation with various behavioral changes (r = 0.7 to 0.9, P < 0.01). The dementia score correlated significantly (r = 0.6 to 0.8, P < 0.01) with all the brain lesions studied, except one, i.e. demyelination (r = -0.4, P > 0.05). These results suggest that a questionnaire can be used to diagnose Alzheimer-like changes in canine practice. Oxidative damage on a cellular and a nuclear level plays an important role in behavior changes.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2004

EEG synchronization likelihood in mild cognitive impairment and Alzheimer's disease during a working memory task.

OBJECTIVE: Synchronization likelihood analysis of resting state EEG has shown that cognitive dysfunction in Alzheimer's disease (AD) and its precursor mild cognitive impairment (MCI) are associated with a loss of functional connectivity in high (upper alpha and beta) frequency bands. Working memory tasks are known to change functional connectivity, but it is unknown whether this increases the differences between AD, MCI and healthy controls. Our objective was to investigate the behavior of synchronization likelihood of multichannel EEG in AD, MCI and cognitively healthy controls, both at rest and during a working memory task. METHODS: EEGs (200 Hz sample frequency, 21 channels, average reference) were recorded at rest as well as during a visual working memory task in 14 patients with AD according to the NINCDS-ADRDA criteria (mean age 76.4; SD 13.6), 11 patients with MCI according to the criteria of Petersen (mean age 78.4; SD 6.4) and 14 with subjective memory complaints but no demonstrable memory disturbance (mean age 61.6; SD 26.6). The synchronization likelihood was computed over 19 channels, comparing each channel with all the other channels for the 0.5-4, 4-8, 8-10, 10-12, 12-30, 30-50 Hz frequency bands. RESULTS: The synchronization likelihood was significantly decreased in the upper alpha (10-12) and beta (12-30) bands in AD compared to persons with subjective memory complaints. The working memory task scores strongly correlated with Mini-Mental State Examination scores. During the working memory task the synchronization likelihood was significantly higher in MCI compared to the control subjects in the lower alpha band (8-10 Hz). CONCLUSIONS: Decrease of beta band synchronization occurs in mild AD, both in a resting condition and during a working memory task. SIGNIFICANCE: Decrease of beta band synchronization in mild AD is a robust finding. The present study confirms our findings in a different cohort of patients, using alternative frequency bands. The diagnostic value of the synchronization likelihood in AD and MCI needs to be further established.

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PubMed2005

On the trail of a cognitive enhancer for the treatment of schizophrenia.

The aim of this critical review is to address that the study of cognition and antipsychotics is not always driven by logic and that research into real pro-cognitive drug treatments must be guided by a better understanding of the biochemical mechanisms underlying cognitive processes and deficits. Many studies have established that typical neuroleptic drugs do not improve cognitive impairment. Atypical antipsychotics improve cognition, but the pattern of improvement differs from drug to drug. Diminished cholinergic activity has been associated with memory impairments. Why atypical drugs improve aspects of cognition might lie in their ability to increase dopamine and acetylcholine in the prefrontal cortex. An optimum amount of dopamine activity in the prefrontal cortex is critical for cognitive functioning. Another mechanism is related to procedural learning, and would explain the quality of the practice during repeated evaluations with atypical antipsychotics due to a more balanced blockage of D2 receptors. Laboratory studies have shown that clozapine, ziprasidone, olanzapine, and risperidone all selectively increase acetylcholine release in the prefrontal cortex, whereas this is not true for haloperidol and thioridazine. A few studies have suggested that cholinomimetics or AChE inhibitors can improve memory functions not only in Alzheimer's disease but also in other pathologies. Some studies support the role of decreased cholinergic activity in the cognitive deficits while others demonstrate that decreased choline acetyltransferase activity is related to deterioration in cognitive performance in schizophrenia. Overall, results suggest the hypothesis that the cholinergic system is involved in the cognitive dysfunctions observed in schizophrenia and that increased cholinergic activity may improve these impairments. Furthermore, a dysfunction of glutamatergic neurotransmission could play a key role in cognitive deficits associated with schizophrenia. Further meta-analysis of various clinical trials in this field is required to account for matters on the grounds of evidence-based medicine.

Acetylcholine↗

PubMed2000

Tardive dyskinesia is associated with impaired retrieval from long-term memory: the Curaçao Extrapyramidal Syndromes Study: IV.

Tardive dyskinesia may be associated with cognitive dysfunction. It is not clear whether this dysfunction occurs in the form of a global or specific cognitive deficit. A cross-sectional study was conducted in a well-defined catchment area (Curaçao, The Netherlands Antilles). All schizophrenic inpatients who had been taking neuroleptic medication for at least 3months and who were younger than 65years were included (n=53). Tardive dyskinesia was assessed with the Abnormal Involuntary Movement Scale. The neuropsychological assessment comprised tests of memory, executive function, and speed of information processing. Of the six cognitive measures, only delayed recall was significantly associated with orofacial dyskinesia. Limb-truncal dyskinesia was not associated with any of the cognitive measures. The pattern of memory impairment is consistent with there being a frontal-subcortical disturbance in orofacial dyskinesia. The results underscore the importance of using specific cognitive test procedures in the search for the cognitive correlates of dyskinesia.

Basal Ganglia Diseases↗

PubMed1997

ERP assessment of visual and auditory language processing in schizophrenia.

Language disturbance in schizophrenia has been recently attributed to disturbed priming mechanisms. In the present study, event-related potentials (ERPs), were recorded to final words in sentences presented to 13 chronic patients with schizophrenia and 12 normal controls. Half of the final words fit a sentence context and another half did not. The N400 (the ERP sensitive to language) latency was prolonged, and its amplitude was more negative to both correct and incorrect sentence endings in the group with schizophrenia relative to the group of normal controls. The early ERP components, N100 and P200, were similar in both groups. These results suggest that language abnormalities in schizophrenia are related to a dysfunction in the language system and not to a general cognitive dysfunction, and may be related to poor use of context in patients with schizophrenia.

Adult↗

PubMed2001

A study of mismatch negativity in newborns.

BACKGROUND: Although newborns are presumed to have cognitive ability, studies on the objective cognitive ability of neonates are making little progress. METHODS: We gave auditory and visual stimuli to newborns whose conceptional age ranged from 35 to 43 weeks and recorded the mismatch negativity (MMN) that is said to reflect the process by which stimuli are detected automatically. We compared the waveform and latency of the MMN. RESULTS: The mismatch negativity waveform in newborns was similar to that of adults. The MMN latency tended to shorten with an advance in conceptional age and was especially shortened between 36 and 37 weeks of fetal life. In some newborns whose clinical course indicated a possibility of their having cognitive dysfunction, the MMN latency was prolonged. CONCLUSIONS: Newborns also have cognitive ability and MMN is useful for objectively evaluating the cognitive ability in newborns.

Cognition↗

PubMed2006

Genetic variation in DTNBP1 influences general cognitive ability.

Human intelligence is a trait that is known to be significantly influenced by genetic factors, and recent linkage data provide positional evidence to suggest that a region on chromosome 6p, previously associated with schizophrenia, may be linked to variation in intelligence. The gene for dysbindin-1 (DTNBP1) is located at 6p and has also been implicated in schizophrenia, a neuropsychiatric disorder characterized by cognitive dysfunction. We report an association between DTNBP1 genotype and general cognitive ability (g) in two independent cohorts, including 213 patients with schizophrenia or schizo-affective disorder and 126 healthy volunteers. These data suggest that DTNBP1 genetic variation influences human intelligence.

Adult↗

PubMed2006

The progression of epilepsy.

Prognosis for seizure control and cognitive development varies considerably among syndromes. Several factors may interact to influence outcome of an epilepsy including a causative etiology, ictal and interictal discharges, seizure-related trauma or systemic perturbations, and antiepileptic drug (AED) effects. Clinical evidence convincingly supporting Gowers' hypothesis that seizures beget seizures is lacking. Short-term seizure suppression by early treatment does not appear to influence long-term prognosis. Malignant epilepsy syndromes usually begin in infancy or childhood, have a high seizure frequency, resist the initial AED, and are often associated with progressive cognitive dysfunction. Prompt management of some severe epilepsy syndromes may lessen cognitive decline. However, aggressive AEDs therapy must be balanced against the potential for cognitive side effects, particularly if multiple AEDs are used. Several experimental paradigms closely parallel human TLE as both have an initial precipitating injury (IPI), a latent period, then recurrent spontaneous seizures. In humans, an IPI is any medical event with neurological implications. Although transition from a latent period to a seizure disorder certainly constitutes "progression" of the disorder, convincing clinical evidence of subsequent worsening has not emerged. Substantial clinical and experimental evidence indicates some cognitive regression and focal atrophy with time for TLE and other intractable syndromes. However, seizure frequency and severity, established early in the disorder, appear stable in most patients, and even regress in benign syndromes. Factors mitigating or extinguishing epilepsies need to be further sought.

Adolescent↗

PubMed1999

Orthostatic hypotension and cognitive decline in older people.

OBJECTIVES: To establish the role of orthostatic hypotension (OH) as a risk factor for cognitive decline among home-dwelling and institutionalized older people and to describe other predictors of cognitive decline. DESIGN: Follow-up study with two clinical examinations. SETTING: A community-based setting in northern Finland. PARTICIPANTS: All of the 1159 people aged 70 or more living in five rural municipalities around the town of Oulu in Northern Finland in 1991. At the time of the follow-up examination, 2.5 years later, 884 of the original participants were alive and 651 were re-examined. MEASUREMENTS: In 1991, 907 people (78.3% of the total population) were tested for orthostatic hypotension, and their cognitive capacity was assessed with the Mini-Mental State Examination (MMSE). The calculation/spelling tasks were excluded from the final version used in the statistical analysis. The re-assessment of cognitive capacity was made on 651 subjects (73.6% of those alive) who had participated in the first examination. The data were analyzed using polychotomous and linear regression analysis models. RESULTS: The prevalence of OH was 28.7%, with no age or sex differences. The mean sum score for the shortened MMSE in 1991 was 21.6 (+/-3.98) for persons with OH and 21.1 (+/-4.08) for non-OH persons. During the follow-up, the sum score declined in the OH group by .44 (+/-2.81) points and in the non-OH group by .83 (+/-3.61) points. No type of OH (systolic or diastolic 1- or 3-minute values or their combination) predicted cognitive decline; the only predictors were old age and low level of formal education. CONCLUSIONS: Orthostatic hypotension is a common clinical condition that affects every fourth person aged 70 years or older. By temporarily inducing cerebral hypoperfusion, it may cause or exacerbate cognitive dysfunction. In an unselected population, OH was not associated with cognitive deterioration, nor did it predict cognitive decline during a 2-year follow-up.

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