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Neurotoxicity in uremia.

The dialysis patient is aware that his behavior evokes reciprocal and complicating responses from important people in his environment. These interactions are perceived and conducted by neurochemical mechanisms which may be impaired in the abnormal chemical environment imposed in renal failure. It is the behaviors we comprehend as indicators of disordered nervous mechanisms. Therefore, it is logical that neurophysiological and neurobehavioral phenomena should be measured quantitatively in order 1) to estimate objectively the patients' success in achieving the goal of maintenance dialysis treatment, 2) to assess the comparative adequacy of dialysis regimens and 3) to provide objective endpoint measures which are relevant to uremia for further investigations of the etiology and pathogenesis of these critically significant uremic manifestations. Our experimental results illustrate that: 1) measures of conduction velocity, distal latency and response amplitudes, as employed by us, were relatively insensitive in the patients and circumstances studied; 2) several neurophysiological measures, i.e., the spontaneous EEG, VER latency and, perhaps, photic stimulation, on the other hand, are highly correlated with the severity of renal failure; 3) behavioral measures of sustained attention and alertness (TMT), of short-term memory (ASTM) and of cognitive manipulation of symbols (AR) are also highly correlated with the severity of renal failure; 4) some measured abnormalities improve following dialysis, but not always to normal--three residual impairments may indicate dialysis in adequacy; 5) several of these measures can provide objective evidence for adequacy of dialysis and other clinical and treatment effects in patients with renal failure.

Auditory Cortex↗

[Long-term effects of the treatment with risperidone versus conventional neuroleptics on the neuropsychological performance of euthymic bipolar patients].

INTRODUCTION: An increasing number of studies point to the persistence of cognitive deficits in a subpopulation of euthymic bipolar disorders. Atypical antipsychotics represent an interesting alternative treatment compared with conventional neuroleptics, because the former might cause lesser affection of cognitive functions. The objective of this study was to establish, for euthymic bipolar patients who need long-term antipsychotic treatment, the neuropsychological and outcome (occupational functioning) differences between the patients treated with risperidone and the patients treated with conventional neuroleptics. SUBJECTS AND METHOD: A sample of twenty RDC bipolar I and II patients were assessed by means of the SADS. All of them were euthymic (HDRS < 8; YMRS < 6) for at least 6 months and treated with antipsychotics. Patients who received risperidone (N = 11) were compared with patients who received conventional neuroleptics (N = 9) with respect to their neuropsychological profile. RESULTS: There were significant differences in Trail Making Test-part B (p = 0.038) and in occupational outcome (p = 0.024), favouring patients who were treated with risperidone. There were no significant differences in other neuropsychological tests, but the patients treated with risperidone tended to score higher in most measures of cognitive performance. CONCLUSIONS: Among bipolar patients who need long-term antipsychotic treatment for preventing relapses, patients who receive risperidone show more cognitive flexibility and better occupational adaptation than patients treated with conventional neuroleptics.

Adult↗

[Aggressiveness and residual schizophrenia].

The authors study aggression behaviour in a sample of 20 patients with residual schizophrenia, using the Instrument I for the measure of aggression, developed by professors Ledesma, Rodrigues and Izquierdo. A pattern of aggression has been found among residual patients characterized by a decrease of global aggressiveness and hetero-aggressiveness, compared with a control group. It has also been found a low psychomotive potential and small psychomotive aptitude reactivity. We are of the opinion that the aggressiveness pattern among residual schizophrenia is due to a defect personality, with an organic cerebral base.

Aged↗

Sucrose and delinquency: behavioral assessment.

In this study, a double-blind challenge design was used to evaluate the hypothesis that sucrose ingestion may compromise the behavioral performance of juvenile delinquents. Subjects were 58 white delinquents, 57 black delinquents, and 39 white nondelinquents. The behavioral assessment included tasks that are relevant to delinquency and that might be expected to be disrupted following sucrose ingestion. The results provide no evidence that sucrose ingestion impairs the performance of juvenile delinquents. In fact, the results of several analyses indicated that the sucrose breakfast was associated with improved performance. In additional analyses the effect of sucrose on particular subgroups of juvenile delinquents was evaluated. Statistical interactions indicated that the performance of delinquents rated as more behaviorally disturbed benefited from sucrose ingestion, whereas those delinquents with less pronounced behavior problems tended to show impaired performance following a sucrose-loaded breakfast. These results indicate that simple statements regarding the effects of sucrose ingestion on behavior are likely to be misleading and highlight the need to consider individual difference variables when investigating the effects of sucrose on juvenile delinquents.

Adolescent↗

Estrogen replacement therapy and postural stability in the elderly.

Postural instability and falls in the elderly patient constitute a major health care problem. The etiology is often multifactorial, involving abnormal sensory input (visual, vestibular, and somatosensory), poor central processing, and suboptimal musculoskeletal biomechanics. Estrogen replacement therapy has been shown to prevent Alzheimer's disease and to improve cognitive performance in women with dementia. It was, therefore, postulated that estrogen replacement may improve central processing speed, which would result in improved postural stability. In this prospective, randomized, double-blinded study, 87 elderly female subjects (age > 69) were examined by repeated dynamic platform posturography, to measure the effect of estrogen therapy versus placebo upon postural stability. Results indicate that those receiving estrogen had no significant improvement in postural stability at 2 and 8 months of treatment relative to those receiving placebo. Trail Making B test was used as the psychometric test of central processing speed. There was no significant effect of estrogen on this measure over the 8 months of observations. It is concluded that 8 months of estrogen replacement therapy has no significant effect on central processing speed or postural stability in a healthy older female population.

Aged↗

Children's color trails.

Color Trails for Children was developed in response to the need for instruments which minimize cultural bias in neuropsychological testing. The test, similar in format to Trail Making, was designed to provide an evaluation of speeded visuomotor tracking while minimizing the influence of language. The present research involves two exploratory studies which examine the relationship between Color Trails for Children and Trail Making, factors that may affect performance times, and discriminant validity. Results indicate that the tests appear to measure the same neuropsychological domains, and administration of Trail Making did not significantly alter performance times on Color Trails. Increasing age and IQ were related to quicker completion time for both tests. Females were found to complete Color Trails 2 and Trail Making Part B more quickly than males in this sample. Comparison between children diagnosed with learning disabilities, attention deficits, or mild neurological conditions and a preliminary standardization sample supported the discriminant validity of Color Traits to distinguish between normal controls and children with altered neuropsychological functioning. Comparison between clinical conditions indicated that Color Trails 2 was particularly sensitive in discriminating among the groups. Although further research is needed, results suggest that Color Trails has the potential to be an effective research and clinical tool in child neuropsychological assessment.

Journal Article↗

Patterns of neuropsychological deficits that discriminate schizophrenic individuals from siblings and control subjects.

Previous research on persons with schizophrenia and their relatives suggests two independent etiologic factors may combine to produce schizophrenia, and these factors may be indexed respectively by independent neuropsychological tests. Two neurocognitive measures, the Trail Making and Wisconsin Card Sorting (WCST) tests, were administered to 28 schizophrenic subjects, 15 nonschizophrenic siblings, and 35 control subjects by investigators blind to DSM-III-R diagnoses. Results support key predictions of a two-factor model: 1) having poor scores on both tests discriminated schizophrenic individuals from both siblings and control subjects, and 2) poor Trail Making and WCST performance were inversely associated among schizophrenic individuals' non-schizophrenic siblings.

Adult↗

Evidence for genetic mediation of executive control: a study of aging male twins.

The objective of this study was to investigate the genetic and environmental influences on indexes of executive control in elderly male twins (members of the National Heart, Lung, and Blood Institute Twin Study). Multivariate genetic modeling was applied to performance on four tests: Digit Symbol Substitution, color--word interference, Trail Making B, and verbal fluency. After exclusion of individuals with a positive stroke history, data were available for 80 monozygotic and 78 dizygotic twin pairs of ages 69--80 years. Performance on all measures was adjusted for age and education. Significant genetic and environmental influences to performance on each measure of executive control were identified (range of heritability = 34%--68%). Multivariate analyses revealed that a model with a latent executive control factor most adequately fit the observed covariances on test performance, chi(2)(58, N = 316) = 69.7, p =.14. The shared executive control factor had a heritability of 79% and accounted for 10%--56% of the genetic variance in performance on each of the four tests. Of the 4 tests examined in this analysis, Digit Symbol Substitution appeared to be the marker of executive control with the largest genetic component, whereas verbal fluency stood out as displaying a pattern of genetic and environmental influences distinct from the other 3 measures.

Aged↗

Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data.

The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer's Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 +/- 5 years; mean educational level 10 +/- 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.

Aged↗

Cognitive impairment of acute mountain sickness and acetazolamide.

In a trial to assess the cognitive impairment attributable to benign acute mountain sickness (AMS) and to acetazolamide, six women and five men, 20-35 years old, ascended from sea-level to 3600 m in 36 h and were assessed for deterioration in performance on psychological tests. Of five sex-matched pairs with a mean age difference of 3.4 years (S.D. +/- 4.4 years), one member took slow-release acetazolamide 500 mg daily and one placebo on a double-blind basis during the ascent and again for an identical course at low altitude 32-38 d later. The unmatched woman took placebo during ascent. Before, during, and after each drug course each subject performed an Environmental Symptom Questionnaire (ESQ) and a psychological test battery consisting of trail-making, paced auditory serial addition test (PASAT), letter-digit code, dual-task cancellation and subtraction, and memory subtests. On ascent, ESQ score deteriorated by an average of 62 points in placebo subjects compared with 32 in acetazolamide subjects (p = 0.055). Deterioration in the psychological test battery was only significant in the PASAT (p less than 0.05) and memory (p less than 0.01) subtests of subjects taking placebo. For those taking acetazolamide, no test showed significant impairment, suggesting it had no detectable cognitive impairment at this dose.

Acetazolamide↗

Differential relationships between positive and negative symptoms and neuropsychological deficits in schizophrenia.

UNLABELLED: This study assessed the relationships between positive and negative clinical symptoms and specific neuropsychological deficits in a group of stable schizophrenic patients. METHOD: Thirty patients were assessed using the Positive and Negative Syndrome Scale (PANSS) for schizophrenia and a battery of cognitive tests. The PANSS assessments were done by a group of raters blind to the results of cognitive tests, while the cognitive tests were conducted by a different group of raters who remained blind to the PANSS scores. RESULTS: We found that, although positive and negative symptoms showed a trend toward direct correlation with each other, they correlated with distinct cognitive deficits. Patients with higher negative scores had more perseverative responses, perservative errors, and completed fewer categories on the Wisconsin Card Sorting Test; they also experienced more difficulties on trail making and verbal fluency tests. On the other hand, positive symptoms were associated with poor performance on the Digit Span, particularly the Digit Span Forward. CONCLUSIONS: Our findings are in agreement with previous reports that negative symptoms may be associated with poor performance on cognitive tests reflecting particularly frontal function. Positive symptoms, on the other hand, seem to be associated with poor attention, specifically of auditory type, and thus, possibly with dysfunction within the more widespread neural networks underlying attention. Our findings support the hypothesis that positive and negative symptoms may be associated with distinct neuropsychological deficits and thus with distinct neurological substrates and point to the need to address both positive and negative dimensions when studying schizophrenia.

Adult↗

Cognitive flexibility in anorexia nervosa and bulimia nervosa.

The aim of this study was to determine if there are differences in cognitive flexibility in anorexia nervosa and bulimia nervosa. Fifty-three patients with an eating disorder (34 with anorexia nervosa and 19 with bulimia nervosa) and 35 healthy controls participated in the study. A battery of neuropsychological tests for cognitive flexibility was used, including Trail Making B, the Brixton Test, Verbal Fluency, the Haptic Illusion Test, a cognitive shifting task (CatBat) and a picture set test. Using exploratory factor analysis, four factors were obtained: 1: Simple Alternation; 2: Mental Flexibility; 3: Perseveration; and 4: Perceptual Shift. Patients with anorexia nervosa had abnormal scores on Factors 1 and 4. Patients with bulimia nervosa showed a different pattern, with significant impairments in Factors 2 and 4. These findings suggest that differential neuropsychological disturbance in the domain of mental flexibility/rigidity may underlie the spectrum of eating disorders.

Adult↗

Short-term and long-term memory in elderly patients with NIDDM.

OBJECTIVE: To determine cognitive and memory dysfunction associated with non-insulin-dependent diabetes mellitus (NIDDM) and its relationship with depression, metabolic control, and serum lipids. RESEARCH DESIGN AND METHODS: We studied a well-characterized group of 20 elderly patients with NIDDM and 22 control subjects with normal glucose tolerance recruited from a larger population-based sample. In addition to clinical and laboratory examinations, self-rating questionnaires that assess minor psychiatric disorder (General Health Questionnaire) and depression (Zung scale) were completed by patients and control subjects. Memory was examined with digit and block-span tests, word-list learning, Heaton Visual Memory Test, and Moss Visual Span Test. Executive functions were examined by Trail-Making A and B test and by Verbal and Category Fluency Tests. Visuoconstructive reasoning was examined with the block design subtest of the Wechsler Adult Intelligence Scale. RESULTS: The NIDDM patients showed preserved memory span, but poor performance in learning tasks compared with control subjects. The patients recalled no fewer words than the control subjects, but the process of of learning seemed to be different in the two groups. The recognition of the learned words was not impaired. Elevated serum total and very-low-density lipoprotein triglyceride levels, measured either before examinations or 5 or 10 years earlier, were associated with effects on retrieval from semantic memory in NIDDM patients. CONCLUSIONS: The NIDDM patients had impaired control of their learning processes. Elevated serum triglyceride levels may be related to control of mental processing in diabetic patients.

Adult↗

Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy.

Patients with schizophrenia show impairments of attention and neuropsychological performance, but the extent to which this is attributable to antipsychotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), the antipsychotic serum concentration of dopamine (DA) D2-blocking activity and the approximated central dopamine D2-receptor occupancy (DA D2-occupancy), on conditioned blocking (CB) measures of attention and performance on a neuropsychological battery, in 108 patients with schizophrenia (compared with 62 healthy controls). Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid versus non-paranoid diagnosis, and in female versus male patients (independent of symptom severity). Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance of the trail-making and picture completion tests (negative) and the block-design task (positive) showed the functional importance of DA-related activity. High estimates of central DA D2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study of its kind, tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recall) as well as in some non-verbal abilities mediated more in the right hemisphere in patients with schizophrenia.

Adult↗

Therapeutic psychosocial intervention for elderly subjects with very mild Alzheimer disease in a community: the tajiri project.

Elderly subjects with mild memory impairment but not apparent dementia are the focus of early intervention trials. To examine the effects of structural psychosocial intervention for elderly subjects with very mild Alzheimer disease, i.e., Clinical Dementia Rating 0.5. The design is a prospective study. The experimental group (14 Clinical Dementia Rating 0.5 subjects) and the control group (11 Clinical Dementia Rating 0.5 subjects) were studied. Subjects with cerebrovascular disease as shown by magnetic resonance imaging were excluded. The experimental group participated in activities in a day-care-like setting once a week over a period of 6 months, whereas the control group did not. Each group was reevaluated after approximately 9 months. The effects of intervention were evaluated by cognitive tests, affective scales, a global clinical measure, an observation scale in the sessions, and a projective test. The experimental group showed a significant improvement on the word fluency test, whereas the control group showed a significant decline on the Mini-Mental State Examination, the digit span, and the Trail Making-A test. The experimental group revealed significantly higher levels on the Mini-Mental State Examination and the digit span compared with the control group after the 6-month intervention. A significant improvement was found for the global clinical measure, the observation scale, and the projective test in the experimental group after the intervention. After controlling the potential confounders (age, educational level, baseline cognitive, and affective status) in a multiple regression analysis, the same results were found. We considered that psychosocial intervention had beneficial effects for subjects with very mild Alzheimer disease.

Activities of Daily Living↗

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↗