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Effects of low levels of lead exposure on cognitive function--a review.

The relationship between low levels of lead and cognitive functioning in animals is reviewed. The data suggest that within animals lead can produce a massive disruption of learning ability while not affecting either morbidity or mortality. Concentration of lead appears to insidiously cause damage to learning function where extremely low doses disrupt the hard-to-measure higher levels of cognitive function. It is concluded that the current standards of lead concentration should be reappraised in terms of measures of damage to cognitive learning.

Animals

Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy.

INTRODUCTION: The effect of antiepileptic drugs (AED) on cognitive function was studied in 87 patients with epilepsy. MATERIAL AND METHODS: Group A: (n = 52) started AED treatment (carbamazepine, oxcarbazepine, sodium-valproate, phenobarbital or phenytoin). Group B: (n = 27) had AED monotherapy withdrawn (carbamazepine or sodium-valproate). Group C: (n = 8) was switched from phenytoin to carbamazepine monotherapy. The patients were tested before and 4 months after change of the treatment. RESULTS: In group A the test performances were in general unchanged. Patients who had their drug treatment withdrawn (group B) and the patients who were switched from phenytoin to carbamazepine (group C) improved in single tests. The predominant changes in performance seem to be due to practice effect. CONCLUSION: Cognitive functions are only minimally influenced by AEDs after short-term treatment whereas there is a slight improvement after discontinuation of long-term administration of carbamazepine and valproate. A lack of practice effect might be the first indicator of a negative effect of AED on cognitive function.

Adolescent

Cognitive functioning in biological subtypes of depression.

This study describes a method for investigating clinical correlates of biological subtypes of depression, using cognitive functioning as the principal behavioral variable. Dexamethasone Suppression Test (DST) escapers were compared to DST suppressors and healthy controls on a battery of learning and memory procedures designed to investigate cognitive functioning in detail. DST suppressors, but not escapers, were cognitively impaired on our tasks. The performance of controls and DST escapers was related to depth of semantic processing, whereas performance of DST suppressors varied inversely with degree of felt hopelessness. Examination of cognitive functioning in future studies may provide useful insights into the clinical significance of biological markers of depression.

Adult

Animal models of cognitive function.

Various of animal models of cognitive function have been developed both to discover neural processes underlying cognition and to develop and test novel therapeutic interventions. Lesion models used in basic research have specified brain circuits involved in discrete cognitive behaviors, and simple system models have identified electrophysiological and biochemical events that might mediate processes such as learning and memory. Models used for drug screening for potential cognition enhancers have been less successful. Drug-screening models have identified several compounds as being of potential use as treatments for cognitive dysfunction prominent in conditions such as Alzheimer's disease. Unfortunately, most of these compounds have not been successful in clinical studies. This paper reviews representative model systems used for basic research and provides a more extensive treatment of models used to screen drugs, with an emphasis on models that attempt to mimic the cholinergic hypofunction characteristic of Alzheimer's disease. Included also are evaluations of the utility of models for drug screening and a discussion of possible reasons for discrepancies between preclinical and clinical evaluations of potential cognition enhancers.

Animals

Effect of advanced brain atrophy and vitamin deficiency on cognitive functions in non-demented subjects.

The relationship between the cognitive functions, structural changes of the brain and vitamin levels was evaluated in 36 non-demented subjects with advanced brain atrophy, and 57 age- and sex-matched healthy controls. In the control subjects ageing was associated with mild decline of cognitive skills, but the cognitive changes were not linked to the structural changes of the brain. In contrast, advanced brain atrophy and vitamin deficiency was related to the decline of complex cognitive functions in the atrophy group. Our results indicate that there are limits of normal age-related changes of the brain structure, and advanced brain atrophy on CT scans increase the probability of mild deficits of the cognitive skills.

Aged

Effects of early intervention on cognitive function of low birth weight preterm infants.

The Infant Health and Development Program is a randomized clinical trial to test the efficacy of educational and family support services and pediatric follow-up, offered during the first 3 years of life, in reducing the incidence of developmental delay in low birth weight preterm infants at eight clinical sites (N = 985). It was hypothesized that larger intervention effects would be found for the domains in which low birth weight preterm infants are known to have problems, specifically visual-motor and spatial skills and receptive language skills. These analyses explore the effects of the Infant Health and Development Program on different domains of cognitive functioning. Cognitive domains are identified by means of factor analysis of the intelligence tests used at 12, 24, and 36 months (Bayley Scales of Infant Development (including the Mental and Motor scales) at 12 and 24 months; the Stanford-Binet, Peabody Picture Vocabulary Test, and Beery Test of Visual Motor Intergration at 36 months). Our results reveal that, although intervention benefits accrue across cognitive domains at 24 and 36 months, gains are most pronounced for receptive language and visual-motor and spatial skills.

Child Development

Sodium valproate and cognitive function.

The literature concerning the effects of sodium valproate on cognitive function was reviewed, including both volunteer and patient studies. Two were reported from the National Hospital--one a double-blind crossover investigation against placebo in volunteers, and the other in patients on monotherapy. It was concluded that sodium valproate has minimal adverse effects, although those that are seen are probably dose related. It has less of an effect on cognitive function than some of the other commonly used anticonvulsants.

Adolescent

Nutritional factors in physical and cognitive functions of elderly people.

The quality of life of aging individuals depends profoundly on their capacity for physical mobility, mental alertness, and cognitive function. Independence and self-esteem are strongly determined by physical and mental capacities. Stimulated by reports of declining function with age, investigators have examined the relationships between lifestyle factors and maintenance of functional status. Growing evidence supports the view that continued physical activity and good nutritional status are important determinants of physical and cognitive function. It is possible that some of the decline in cognitive function associated with aging is preventable or reversible with improved vitamin nutriture, especially vitamin B-12, vitamin B-6, and folate. It might well be argued that the most practical outcome of research on the relationship of diet and nutrition to the aging process would be a better understanding of the ways in which our behavior can maintain a vigorous quality of life.

Aged

Effects of altitude on mood, behaviour and cognitive functioning. A review.

Alterations in psychological mood, personality, behaviour and cognitive functioning associated with altitude have been recognised for many years. Psychological and behavioural changes resulting from the effects of hypoxia often include increases in euphoria, irritability, hostility and impairment of neuropsychological functions such as vision and memory. There is limited research to indicate that some decrements may persist for up to a year, or longer, after return to lower elevation. However, generalisations of the effects of altitude on mood, behaviour and cognitive function are complicated by differences between studies including the specific tasks or dimensions measured, methods of measurement, degree of altitude, duration of exposure and types of participants. There also appear to be wide individual differences in the response to altitude sojourns. Investigations designed to measure symptoms and mood changes during actual mountain climbs are needed, since most of the systematic research has been conducted in altitude chambers. The extent to which these simulations can be generalised to actual altitude settings remains to be documented.

Affect

Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine.

Cognitive functions and psychopathology were assessed in 36 treatment-refractory schizophrenic patients before initiation of clozapine, and at 6 weeks and 6 months, thereafter. Before treatment, cognitive impairment was found in each measure of memory, attention, and executive function as compared with 26 normal controls. After both 6 weeks and 6 months of treatment, significant improvement occurred in the Controlled Oral Word Association Test, a measure of retrieval from reference memory. Improvement was also noted at 6 months in the Category Instance Generation Test, another measure of retrieval from reference memory, and in some, but not all, tests of executive function, attention, and recall memory. Clozapine treatment also resulted in significant improvement in Brief Psychiatric Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month assessment points. There was some evidence for a relationship between improvement in psychopathology and cognitive function. The improvement in cognitive function during clozapine treatment could have consequences for capacity to work and social function.

Adult

Cognitive functions and quality of life in patients with low-grade gliomas: the impact of radiotherapy.

The role of early radiotherapy in the treatment of low-grade gliomas is controversial. For this reason the impact of radiotherapy on quality of life was studied in long-term survivors of biopsy-proved low-grade gliomas without signs of tumor recurrence. Twenty patients (age range, 18-66 years) had been treated with early radiotherapy; the other 21 patients (age range, 19-65 years) had undergone surgery or biopsy only. The interval from diagnosis to testing ranged from 1 to 12 years (mean, 3.5 years). Nineteen patients with low-grade hematological malignancies, surviving 1 to 15 years without central nervous system involvement, served as control subjects. Apart from the neurological and functional status, the patients' cognitive, affective, and psychological status was determined. None of the survivors had significant neurological impairment and the Karnofsky index for them was at least 70. However, more specific examinations of cognitive functions and the affective status (Profile of Mood States) indicated that, compared to the control subjects, the patients with low-grade gliomas had significantly more cognitive disturbances and suffered more frequently from fatigue and depressed moods. The two groups with low-grade gliomas, on the other hand, did not differ significantly on any of these measures. It is concluded that radiotherapy did not cause these disturbances and had no negative impact on quality of life in these patients.

Adolescent

Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function.

OBJECTIVE: To assess whether fluvoxamine alters the pharmacokinetics of alcohol or potentiates alcohol-related impairment of cognitive function. METHODS: The study design required partially "blinded" balanced crossover studies, each involving 12 healthy male volunteers who each received a 40 gm dose of intravenous or oral alcohol after single and multiple doses of 50 mg fluvoxamine. Main outcome measures for pharmacokinetics were venous blood alcohol and plasma fluvoxamine. Main outcome measures for pharmacodynamics were word recall, simple and choice reaction time, number vigilance, memory scanning, and word recognition. RESULTS: The pharmacokinetics of intravenous alcohol were not affected by concomitant administration of fluvoxamine. Compared with placebo-alcohol, alcohol slightly increased the rate of fluvoxamine absorption, but the area under the plasma concentration-time curve from 0 to 12 hours at steady state was unchanged. As expected, alcohol significantly impaired cognitive function in volunteers. However, fluvoxamine did not potentiate the effects of alcohol and in some instances appeared to reverse the effects or reduce their duration. Fluvoxamine was well tolerated: only mild adverse effects were reported, and none of those required intervention. CONCLUSION: Fluvoxamine does not interact significantly with alcohol or potentiate alcohol-related impairment of cognitive function.

Administration, Oral

Relations of cognitive functions associated with the frontal lobes and learning disorders in children.

Various cognitive processes associated with the frontal lobes and their influence upon learning and learning disorders in children were investigated. Subjects were 29 7- to 12-yr.-old boys and girls. Analysis of variance suggested that, as a group, the learning-disabled children scored lower on tasks with a high demand for selective attention, ability to inhibit interference, sequential reasoning, and integration and organization of new information--cognitive functions commonly attributed to the frontal lobes. The relationship of these cognitive functions to acquisition of basic academic skills is discussed.

Child

Ventricular size, cognitive function and depression in patients with multiple sclerosis.

The purpose of this study was to explore further the hypothesis that changes in cognitive function may occur in the mild stages of multiple sclerosis (MS) by determining whether ventricular enlargement was related to cognitive function. Ten measures of ventricular size were made in a sample of 123 MS patients with mild disability and 60 well-matched healthy controls. In addition, sixteen tests of cognitive function and the Beck Depression Inventory were administered. For the MS group, there were significant correlations between the ventricular measures and cognitive performance but not for the normal controls. Scores on the Beck Depression Inventory were not correlated with either cognitive performance or ventricular enlargement. These findings suggest that for the MS group cognitive impairment was related to the disease process but not to the level of depression.

Adult

The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease.

OBJECTIVE: To determine the effect of treatment with Ginkgo biloba extract on objective measures of cognitive function in patients with Alzheimer disease (AD) based on formal review of the current literature. METHODS: An attempt was made to identify all English and non-English-language articles in which G. biloba extract was given to subjects with dementia or cognitive impairment. Inclusion criteria for the meta-analysis were (1) sufficiently characterized patients such that it was clearly stated there was a diagnosis of AD by either Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, or National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, or there was enough clinical detail to determine this by our review; (2) clearly stated study exclusion criteria, ie, those studies that did not have stated exclusions for depression, other neurologic disease, and central nervous system-active medications were excluded; (3) use of standardized ginkgo extract in any stated dose; (4) randomized, placebo-controlled and double-blind study design; (5) at least 1 outcome measure was an objective assessment of cognitive function; and (6) sufficient statistical information to allow for meta-analysis. RESULTS: Of more than 50 articles identified, the overwhelming majority did not meet inclusion criteria, primarily because of lack of clear diagnoses of dementia and AD. Only 4 studies met all inclusion criteria. In total there were 212 subjects in each of the placebo and ginkgo treatment groups. Overall there was a significant effect size of 0.40 (P<.0001). This modest effect size translated into a 3% difference in the Alzheimer Disease Assessment Scale-cognitive subtest. CONCLUSIONS: Based on a quantitative analysis of the literature there is a small but significant effect of 3- to 6-month treatment with 120 to 240 mg of G. biloba extract on objective measures of cognitive function in AD. The drug has not had significant adverse effects in formal clinical trials but there are 2 case reports of bleeding complications. In AD, there are limited and inconsistent data that preclude determining if there are effects on noncognitive behavioral and functional measures as well as on clinician's global rating scales. Further research in the area will need to determine if there are functional improvements and to determine the best dosage. Additional research will be needed to define which ingredients in the ginkgo extract are producing its effect in individuals with AD.

Alzheimer Disease

The cumulative effect of neglect and failure to thrive on cognitive functioning.

OBJECTIVE: A cumulative risk model was used to examine the relationship among neglect, failure to thrive (FTT), and cognitive functioning in low income children. METHOD: A sample of 177 children 3 to 30 months old was recruited from a pediatric clinic serving low-income, primarily African American families. Four groups were formed based on neglect and FTT status: Neglect and FTT, Neglect Only, FTT Only, and No Neglect or FTT. FTT was defined as weight-for-age below the 5th percentile on growth charts. To avoid the biases associated with Child Protective Service reports as definitions of neglect, the HOME scale (Caldwell & Bradley, 1984) was used to define neglect. RESULTS: The cognitive performance of the group with neglect and FTT was significantly below that of the children in the Neglect Only, FTT Only, and No Neglect or FTT groups. CONCLUSIONS: These findings support a model in which the accumulation of risk factors is detrimental to cognitive functioning. The results also underscore the need for thorough evaluation when one risk factor has been identified. Growth failure may come to the attention of medical personnel, but neglect may not be detected. However, a child experiencing both neglect and FTT may be at risk for significant deficits in cognitive functioning.

Child Abuse

Cognitive functions in subjects with incidental cerebral hyperintensities.

We investigated the association between incidental cerebral hyperintensities (CH) found by magnetic resonance imaging (MRI) and cognitive functions in neurologically normal, nondemented subjects. Semiquantitative scores for MRI lesions and those for brain atrophy were compared with the results of extensive cognitive examinations using multivariate analysis. There was no correlation between CH and cognition, except that periventricular hyperintensities, especially those in posterior locations, were associated with reduced performance in the Stroop test. Overall cognitive functions were associated with age, and age was a predominant factor in the prefrontal functions. Brain atrophy was associated more with decline of the posterior and dorsolateral frontal brain functions. We suggest that disturbances in attention and speed may initially result from incidental CH, while other cognitive functions remain unaffected.

Adult

Parasitic helminth infection and cognitive function in school children.

The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica, using a double-blind placebo-controlled protocol. Results were evaluated by using a forward-stepwise multiple linear regression. Removal of worms led to a significant improvement in tests of auditory short-term memory (p less than 0.017; p less than 0.013), and scanning and retrieval of long-term memory (p less than 0.001). Nine weeks after treatment, there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function. It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.

Albendazole