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Beneficial effect of renal transplantation on cognitive brain function.

Cognitive brain dysfunction is a common complication of end-stage renal disease. To investigate the cerebral effect of renal transplantation, we studied P300 event-related potentials--an objective marker of cognitive brain function--trailmaking test and Mini-mental state in 15 chronic hemodialysis patients and 45 matched healthy subjects. Before transplantation, patients showed prolonged P300 latency (364 vs. 337 ms, P < 0.01), smaller amplitude (15.2 vs. 19.1 microV) and scored lower (P < 0.05) in trailmaking test and Mini-mental state as compared to healthy subjects. Following renal transplantation (14 months), P300 latency decreased (337 ms, P < 0.01 vs. before) and amplitude increased (17.4 microV, P < 0.05 vs. before), indicating improved cognitive brain function. The trailmaking test and Mini-mental state tended to improve. Following transplantation, P300 findings, trailmaking test and Mini-mental state were not different from healthy subjects. Additional studies following erythropoietin treatment in 6 of the 15 hemodialysis patients revealed decreased (improved) P300 latency (351 vs. 379 ms before, P < 0.05) with further decrease following transplantation (341 ms, P = 0.06). Our findings indicate that cognitive brain dysfunction in hemodialysis patients may be fully reversed by successful renal transplantation.

Adult↗

Cognitive functioning in young "social drinkers": is there impairment to detect?

Literature on the cognitive effects of nonexcessive alcohol use suggests that relatively high-quantity-per-occasion use may be related to subsequent decreases in sober-state abstracting skills in adults, but provides no clear prediction for youth. The need to identify persistent alcohol-intake effects on cognition is particularly acute for the period of adolescence and young adulthood because even slight damage may impair developmentally significant skills. We examine the relation between multiple measures of neuropsychological status and both continuous and categorical measures of alcohol-use patterns in an age- and sex-stratified sample of 1,308 18-, 21-, and 24-year-olds. The results of correlational and hierarchial regression analyses suggest that cognitive performance bears little direct relation to drinking behaviors in young nonclinical males and females. Although the data provide no strong support for the hypothesis of a causal relationship between alcohol use and cognitive functioning, there is a slight suggestion that frequent high-quantity consumption may become a salient parameter of use as subjects age. Prospective longitudinal data are needed to explore the directional causality of effects.

Adolescent↗

Intelligence and cognitive function in children and adolescents with spinal muscular atrophy.

Spinal muscular atrophy is a chronic disease characterised by loss of motor function. The aim of the study was to analyse cognitive functions in a large group of patients with spinal muscular atrophy. It was hypothesised that their intelligence is comparable to controls, but not above average as previously postulated. Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests). The mean IQ measured with the CPM/SPM tests was 109.6 for the spinal muscular atrophy group, 107.3 for the sibs and 104.1 for the healthy controls (no significant difference). In the older children and adolescents (SPM only) the mean IQ was significantly higher for the spinal muscular atrophy patients (109.6) than for the controls (95.4). The standard score in the 'mental processing composite' scale of the Kaufman-ABC was identical in the spinal muscular atrophy group and controls (103.8). The cognitive profile was relatively homogeneous. However, the older children and adolescents did have a significantly higher verbal IQ (113.8) than controls (104.6) in the Wechsler tests. There were no significant differences in any of the tests among different grades of severity (spinal muscular atrophy types I-III). It can be concluded that children and adolescents with spinal muscular atrophy have a general intelligence in the normal range. By adolescence, environmentally mediated aspects of intelligence are higher in patients with spinal muscular atrophy. It could be speculated that the development of cognitive skills and knowledge is a creative way to compensate the many restrictions due to their physical handicap.

Adolescent↗

Determinants of real-world functional performance in schizophrenia subjects: correlations with cognition, functional capacity, and symptoms.

OBJECTIVE: Impairments in adaptive life skills are a major source of disability in patients with schizophrenia. The relationship between adaptive life skills in real-world settings and performance on neuropsychological tests may be complicated by other factors that interfere with deployment of skills. Assessment of the ability to perform life skills under optimal conditions (i.e., assessment of functional capacity) has been proposed as a means to clarify these relationships. METHOD: The authors examined cross-sectional data from a study of the course of neuropsychological and adaptive life skills of older (age 50-85) schizophrenia patients (N=78). Functional capacity was examined with a performance-based measure (UCSD Performance-Based Skills Assessment), and case managers rated real-world adaptive functions (i.e., interpersonal skills, work skills, and community activities). Neuropsychological performance was assessed with a comprehensive battery, while symptoms were assessed with patient self-report and clinical ratings. RESULTS: Confirmatory path analyses were used to evaluate the effects of neuropsychological performance, functional capacity, and symptoms on the various domains of real-world functioning. Neuropsychological performance predicted functional capacity, which predicted all three domains of real-world functioning. Depression predicted interpersonal and work skills, while negative symptoms affected interpersonal skills independently of other predictors. CONCLUSIONS: Real-world adaptive life skills are predicted by neuropsychological performance, symptoms, and functional capacity. Neuropsychological performance contributes little to the prediction of real-world performance after accounting for functional capacity. In some domains, negative and depressive symptoms influenced real-world performance while not relating to functional capacity or neuropsychological performance.

Activities of Daily Living↗

Analysis of cognitive function in animals, the value of SDT.

The search for a better understanding of cognitive decline in man has lead to the use of increasingly complex procedures in animal research. The analysis of the data generated in such experiments has been greatly facilitated by the wider use of computer assisted techniques. These techniques can only be as good as the hypotheses they are used to test. Signal detection theory (SDT) provides a rational framework within which to work. The procedures are derived from human cognitive neuropsychology and are already used to some extent in primate but to a lesser degree in rodent research. The use of SDT offers two main advantages: first, a testable hypothesis as to the manner in which competing processes arrive at choice between various courses of action; second, the statistical procedures offer clear advantages over more traditional approaches by reducing the chances of misinterpretation. Though relatively easy to apply some care must be exercised in the protocol design and the choice of SDT indices if the full value of the approach is to be achieved. If experimental designs can be developed to include the appropriate use of SDT analysis; both the power of such protocols, and their value in the understanding of cognitive function, will provide a major step forward for animal-based research.

Animals↗

Motor and cognitive functions in newly diagnosed adult seizure patients before antiepileptic medication.

OBJECTIVE: Motor and cognitive functions in patients with partial or generalized onset of seizures were evaluated prior to the administration of antiepileptic medication. MATERIAL AND METHODS: Motor function, attention and memory of 52 consecutive newly diagnosed adult patients with partial or generalized seizures were assessed with neuropsychological tests. RESULTS: Patients with partial onset of seizures did not differ from patients with generalized seizures in tests of motor function or attention, nor in tests of learning and memory. Compared to controls patients with epilepsy performed significantly worse on visual motor tasks, mental flexibility and in delayed visual memory. Within the patient group as a whole lower education, higher age and symptomatic epilepsy with more abnormal CT scan findings tended to associate with worse performance in tests of concentration and mental flexibility and tests of memory. CONCLUSION: These findings indicate that newly diagnosed adult patients with partial or generalized onset of seizures prior to treatment with antiepileptic medication experience some problems in visual motor tasks, mental flexibility and memory even without the numerous risk factors for cognitive deficits in epilepsy. In newly diagnosed patients with epilepsy as a whole symptomatic etiology was associated with somewhat more pronounced cognitive problems.

Adolescent↗

Cognitive functions in Duchenne muscular dystrophy: a reappraisal and comparison with spinal muscular atrophy.

In order to clarify cognitive functions in Duchenne muscular dystrophy (DMD), we performed a new controlled neuropsychological study. IQ (WISC-R), verbal skills (fluency, confrontation naming and syntax comprehension) and memory abilities (BEM) were studied in two matched groups; 24 DMD children and 17 spinal muscular atrophy (SMA) children aged 12-16 yr. A significant difference appeared between the DMD and SMA patients: only in the DMD group were there significant disabilities in certain specific functions and normal scores in others. Despite similar education, the DMD children more often had significantly greater learning disabilities. There were more DMD left-handers. Verbal IQ was significantly low whereas performance IQ was at a normal level. DMD children also performed poorly in reading tasks and in some memory functions such as story recall and verbal recognition. Specific cognitive disabilities in certain DMD children, not seen in SMA children, suggest a relationship with a DMD genetic disorder.

Adolescent↗

Congenital heart disease and cardiac surgery in childhood: effects on cognitive function and academic ability.

OBJECTIVE: To evaluate changes in cognitive and academic functioning following cardiac surgery in children with congenital heart disease. DESIGN: A prospective cross sectional study in which patients were assessed immediately before treatment and 12 months later. PATIENTS: Three groups of children aged 3.5-17 years: a group with congenital heart disease awaiting surgery, another awaiting bone marrow transplantation, and a healthy comparison group. MAIN OUTCOME MEASURES: Intelligence quotient and measures of academic attainment, evaluated with the British Ability Scales. RESULTS: Preoperatively, children with cyanotic lesions showed deficits in comparison with those with acyanotic lesions. Postoperatively, children with cyanotic lesions showed a deterioration in performance and achieved significantly lower scores than those with acyanotic lesions. While there were significant differences between the congenital heart disease and bone marrow transplantation groups preoperatively, these were no longer apparent at follow up. CONCLUSIONS: In contrast to previously published findings, the present results suggest that cardiac surgery does not result in early postoperative improvements in cognitive function for children with congenital heart disease. The nature of the cardiac lesion continues to affect cognitive and academic performance, even after surgery.

Adolescent↗

Apolipoprotein E genotypes and cognitive functions in healthy elderly persons.

OBJECTIVES: We investigated whether apoE genotypes correlate with cognitive functions in clinically healthy persons. METHODS: In 1993 and 1995, we measured information processing speed, delayed free recall and semantic aspects of long-term memory in 227 men and 105 women aged 65 and over, a randomly selected subsample of the prospective Basel Study. Cardiovascular risk factors and education were assessed. RESULTS: E2 were more prevalent in old-old (>75 years, 23.5% vs. 15%) compared to E4 than in young-old (<75 years, 19.3% vs. 23.5%). Taking into account age and education, subjects with epsilon3/epsilon4 or epsilon4/epsilon4 alleles (E4) performed lowest in all 3 tests compared to those homozygous for epsilon3 (E3) or carriers of one or two epsilon2 alleles (E2) (reaction time P = 0.009, free recall P = 0.05, WAIS-R vocabulary P<0.05). In old-old there was a significant difference between E2 and E4 for reaction time (P = 0.02) and free recall (P<0.02) but not for vocabulary (P = 0.086). In all 3 groups there were no significant changes after 2 years. The subgroup with the genotype epsilon2/epsilon4 performed consistently best in the cognitive tests. Cholesterol was significantly increased in the E4 and E3 group compared to the E2 group. CONCLUSION: ApoE genotype correlates with cognitive performance. The increased prevalence of E2 in the old-old and the significantly lower plasma cholesterol levels suggest differential morbidity and mortality as important factors influencing the prevalence of cognitive disorders in late life.

Aged↗

The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia.

OBJECTIVE: Cognitive function and regional cerebral blood flow (rCBF) were studied in negative symptom profile schizophrenic patients by using WCST and SPECT. METHODS: Twenty-one schizophrenic patients who matched the criteria of Andreason's negative symptom profile received SPECT and WCST, and then were treated with clozapine for 8 consecutive weeks. There were 28 and 12 normal subjects as the control groups of WCST and SPECT, respectively. RESULTS: Compared with controls, significantly poorer performance on total trials of category (TT), persevering errors (PE), and non-persevering errors (NPE) of WCST were found in schizophrenia (p < 0.05). The total score of the scale for assessment negative symptoms (SANS) was significantly related with poor TT (r = 0.45, p < 0.01) and PE performance (r = 0.45, p < 0.01). The poor TT, PE, and NPE tasks of WCST and SANS scores in the negative schizophrenic patients were significantly improved through clozapine treatment (p < 0.05). The schizophrenic patients had a significantly lower rCBF in bilateral frontal and temporal lobes and lower change rate of rCBF in bilateral frontal lobes during WCST compared to normal controls (p < 0.05). CONCLUSIONS: Negative symptom profile schizophrenia has cognitive deficits and lower rCBF in bilateral frontal and temporal lobes, which suggests that negative symptom profile schizophrenic patients have hypofrontality. Clozapine can improve negative symptoms and improve cognitive dysfunction, although it cannot improve reduced rCBF in the frontal lobes.

Adult↗

Effects of major depression on the cognitive function of younger and older subjects.

The effects of age and depression on cognitive function were investigated in two groups of in-patient major depressives aged under and over 60 years who were tested when depressed and after recovery. The majority of the tests showed impaired performance during depression with improvement after recovery, and also differences between the two age-groups in both the depressed and recovered phases. However, the older subjects were not more severely affected by depression than the younger subjects. The pattern of impairment associated with depression was different to that associated with older age: depression affected performance on more 'complex tasks', whereas age was associated particularly with slowing on timed tests. This study did not suggest that the impairment from baseline due to the depression is greater in the elderly than in younger subjects.

Adult↗

Cognitive functions and psychopathological symptoms in early-onset schizophrenia.

Type and extent of objectively tested cognitive impairments (attention, verbal fluency, nonverbal reasoning) and their association with self-ratings (Paranoia Depression Scale; Frankfurt Complaint Questionnaire) and clinical assessments (Brief Psychiatric Rating Scale, Scales for the Assessment of Positive Symptoms and Negative Symptoms) of psychopathological symptoms were studied in a sample of 74 adolescents primarily suffering from chronic schizophrenia (DSM-III-R; mean duration of illness = 3.4 years), including 15 patients with a very early onset (< 14 years). Special consideration was given to the differentiation between positive and negative symptoms. In cross-sectional analyses, the schizophrenic adolescents were remarkably impaired in both cognitive functions (attention, reasoning) and psychopathological measures (BPRS, SANS, SAPS). However, factor analysis yielded orthogonal factors for cognitive and psychopathological parameters, and canonical correlation analyses did not find a significant correlation between these two areas. As the degree of objectively measured cognitive impairment in chronic schizophrenic adolescents cannot be predicted by the severity of individual psychopathological symptoms, a multidimensional evaluation of the symptomatology seems to be appropriate. Moreover, premorbid disturbances (motor and/or language developmental disorders) and onset characteristics (age, pattern, subdiagnosis), and their relationship to cognitive impairments were investigated. Premorbid disturbances were confirmed as risk factors for the subsequent occurrence of cognitive impairments.

Adolescent↗

Executive cognitive functioning, alcohol, and aggression: comment on Giancola (2000).

P. R. Giancola (2000) postulated executive cognitive functioning (ECF) as a mechanism to explain the association between alcohol consumption and aggression. Alcohol intoxication disrupts ECF, which heightens the probability of aggression. This is most likely to occur in individuals with low ECF. These propositions are found lacking. The disruption in ECF by alcohol would be greatest among individuals with high ECF, and low-ECF individuals presumably would not experience much further disruption as result of low baseline functioning. These 2 premises appear to be inconsistent. The concept of ECF suffers from the problems associated with hypothetical constructs. Patterns of aggression emerge in young children before the development of cognitive skills associated with ECF, and the association of aggression and low ECF occur as results of environmental risk factors. ECF is neither a necessary nor a sufficient condition to explain aggression following alcohol drinking.

Aggression↗

Cognitive functioning in depression: a review of theory and research.

This paper reviews recent research into cognitive functioning in depression, with particular reference to the theories of Lewinsohn, Beck, Seligman and Klein. The major cognitive changes in depression are a decrease in the ability to maintain concentration and effort, and an increase in the relative salience of aversive events and memories, with a corresponding decrease in the salience of pleasant events. There is as yet little evidence to support the view that depressions arise out of pre-existing depressive attitudes. Attention is drawn to the heterogeneity of depressive disorders, and the significance of the endogenous/non-endogenous distinction is discussed.

Bipolar Disorder↗

The D2 dopamine receptor (DRD2) gene and family stress; interactive effects on cognitive functions in children.

TaqI A D2 dopamine receptor (DRD2) alleles, family stress, and cognitive markers, including visuospatial ability (Benton's Line Orientation) and event-related potentials (P300 amplitude and latency), were obtained in preadolescent boys of alcoholic and nonalcoholic fathers. In the presence of the DRD2 minor allele (A1+), the Family Stress score negatively correlated with the Line Orientation score and P300 amplitude. No significant correlations were found in boys lacking this allele (A1-). The interaction of the A1+ allele and the Family Stress score produced significant regression coefficients for both Line Orientation score (p = .002) and P300 amplitude (p = .04). Together, these two cognitive markers account for 37% of the variance in the Family Stress score of 47 A1 allele boys (p = .0002) but less than 1% in 71 A1- allele boys (p > .9). This provides the first evidence of a specific gene-environment interaction involving human cognitive functioning.

Adolescent↗

Cognitive function is minimally impaired after ambulatory surgery.

PURPOSE: To evaluate the magnitude of subjective cognitive failure in the three days following general anesthesia (GA) for ambulatory surgery. METHODS: After Research Ethics Board approval, 258 patients undergoing general anesthesia (GA) and 250 patients scheduled for local anesthesia (LA) were recruited from our ambulatory surgical unit. Following the method of Tzabar, Asbury and Millar, patients were asked to complete the cognitive failures questionnaire (CFQ) before their procedure (with respect to the previous three days) and on the third postoperative day (with respect to their recovery period). RESULTS: General anesthesia and LA groups were similar in demographic make-up, except that the LA group contained more patients of American Society of Anesthesiologists physical status I (64.5% vs 52.7%, P < 0.05) and had significantly shorter procedure duration (25 vs 51 min, P < 0.01) than the GA group. Median preoperative CFQ scores (interquartile range) were 26 (18) for the LA group and 26 (18) for the GA group. Postoperative CFQ scores were 25 (20) for the LA group and 28 (22) for the GA group. There was no significant difference in preoperative CFQ score between groups (Mann-Whitney U). When preoperative and postoperative CFQ scores were compared, the small increase seen in the GA group was statistically significant (P < 0.05, Wilcoxon). CONCLUSION: A statistically significant impairment of cognitive function in the three days following GA, but not LA was found. However, the magnitude of this impairment was small, and is of doubtful clinical significance. Modern ambulatory anesthesia may cause less delayed cognitive impairment than was previously thought.

Adult↗

Factors influencing cognitive function, sleep, and quality of life in individuals with systemic lupus erythematosus: a review of the literature.

Cognitive dysfunction represents one of several neurological and psychiatric complications of Systemic Lupus Erythematosis (SLE). Additional manifestations of nervous system involvement subsumed under the term neuropsychiatric SLE (NPSLE) include cerebrovascular disorder, seizures, psychosis, acute confusional state, anxiety and mood disorders. Neuropsychological investigations have facilitated the identification and description of cognitive impairment in SLE and NPSLE. Salient findings from studies of SLE-related cognitive dysfunction are reviewed with respect to neuroimaging procedures, indices of disease activity, and potential moderator variables. Data on cognitive functioning are also discussed in reference to other disease aspects including fatigue, sleep disturbance, and impact on health-related quality of life (HRQL). To date, neuropsychological functioning has been studied extensively, albeit separately from other commonly reported SLE-related symptoms. Future research may profit from investigating relationships between cognitive impairment, sleep disturbance and fatigue and their collective impact on functional capacity and quality of life.

Cognition↗

The relationship of sex hormones and cortisol with cognitive functioning in Schizophrenia.

Gonadal as well as stress hormones have recently been implicated in pathophysiology and sex differences in onset, prognosis and treatment of schizophrenia. The present study investigated the effects of serum levels of oestrogen, progesterone, testosterone and cortisol on neuropsychological functioning and psychopathology in a group of 37 patients (17 women, 20 men) with schizophrenia. Neuropsychological measures included tests of attention, verbal abilities, language, memory, executive functioning, motor and speed of information processing. The results showed that oestrogen and age was associated with low positive symptom scores, and within gender, cortisol predicted poor performance on the information processing domain in men. These findings demonstrate that cortisol, in addition to the commonly reported effects of oestrogen, influences neuropsychological functioning in schizophrenia with differential effects on specific domains of cognitive functioning and underscore the need for further investigation of the modulating role of hormones on neuropsychological functioning in schizophrenia.

Adolescent↗