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Cognitive functioning and symptomatology in chronic schizophrenia.

Chronic schizophrenic patients in a long stay hospital were found to have low levels of intelligence (mean IQ of 80), which was attributed to the effects of substantial intellectual deterioration on below average pre-morbid levels of functioning. Patients with the lowest IQ scores had the least severe positive symptoms but symptomatology was not related to age or extent of intellectual decline. Speed of functioning was relatively more impaired than level of intellectual functioning, with cognitive speed being more affected than motor speed. The severity of negative but not positive symptoms was significantly related to the severity of bradyphrenia (cognitive slowing), a result which would be consistent with the notion of a subcortical pathology in patients with Type II schizophrenia.

Adult

Estrogen's impact on cognitive functions in multiple sclerosis.

It has long been suspected that hormonal factors contribute directly and indirectly to the etiology and pathogenesis of multiple sclerosis (MS). The susceptibility of MS is higher in women than in men and women are even more susceptible to hormonal influences when onset occurs at an early or delayed age. Pregnancy has a short-term favorable effect on the course of the disease but there is an increased rate of relapse during the post-partum period. In addition, women often report premenstrual exacerbation of their symptoms with remission during menses. These findings suggest that in women estrogens may exert a stabilizing effect on the clinical manifestations of MS. The role of estrogens is supported also by observations of a higher incidence of cognitive impairment in women than men with MS. A 50 year old woman with a remitting progressive MS experienced profound deterioration in cognitive functions during withdrawal from estrogen therapy which was initiated for the treatment of amenorrhea. Improvement in cognitive functions occurred shortly after she restarted therapy with an estrogen/progesterone preparation and was maintained during long term therapy. Serotonin (5-HT) mechanisms have been implicated in memory functions and estrogens modulate these functions through an interaction with 5-HT2 receptors in the cerebral cortex and limbic system. It is suggested that estrogen withdrawal induces impairment in cognitive functions through dysregulation of 5-HT2 receptor activity and 5-HT neurotransmission. These findings suggest that estrogens have a beneficial influence on cognitive functions in MS patients and that hormonal supplementation might be advised in menopausal and postmenopausal MS patients for the prevention of cognitive deterioration.

Cognition

Longitudinal changes in cognitive functioning in adult day care participants.

This study examines longitudinal changes in cognitive functioning over the course of 2 years in participants of adult day cae programs. Cognitive measures included the Brief Cognitive Rating Scale (BCRS) and the Mini-Mental State Examination (MMSE). Longitudinal data were available for five measurement points over 2 years for 82 participants (22 males and 60 females). Overall, results from this study suggest that there were significant cognitive declines on BCRS and MMSE, even after only 1 or 2 years in the study. The rates of impairment over the 2 years for BCRS and MMSE were highly correlated. Within each measure, the individual rates of decline were very heterogenous and were influenced by the presence, type, and prognosis of dementia. Participants with multi-infarct dementia had greater cognitive decline than did those with other types of dementias. Initial cognitive functioning and physician's prognosis of dementia trajectory were also significant predictors of change over time. Results suggest a floor effect in the BCRS.

Activities of Daily Living

Specialized cognitive function and reading achievement in hearing-impaired adolescents.

This study evaluated the performance of hearing-impaired adolescents on tests of specialized cognitive functioning and explored the linkage between cognitive profile and reading achievement. Other variables noted were mathematics achievement, speech production, etiology, and age of onset of hearing loss. Subjects were 62 severely-to-profoundly hearing-impaired students between 15 and 20 years of age, 31 "high readers" and 31 "low readers." Results indicated that, for this sample, cognitive function was below average for the verbal and sequential skills associated with the left hemisphere but above average for the "visuospatial" skills associated with the right hemisphere. Reading performance proved to be highly correlated with cognitive profile, as did mathematics performance and, to a lesser extent, speech and age of onset. Ramifications for instruction are discussed--in particular, development of strategies for using the right hemispheric cognitive strengths, as identified in this sample, to help overcome the deficits in "verbosequential" processing and reading achievement traditionally associated with hearing-impaired students.

Achievement

Cognitive function in myotonic dystrophy: a follow-up study.

Intellectual and cognitive function were studied in 35 patients with myotonic dystrophy (DM). All 5 patients with the congenital form showed moderate or mild mental retardation. The 30 adult-onset patients had normal intelligence and memory quotients. In this adult-onset group no differences in cognitive function were observed either with respect to sex or physical disability. The sex of the affected parent, mother vs. father, was also without effect in this group. A follow-up study was performed in 16 patients with a mean test interval of 12 years. There was no severe cognitive impairment over this time span or a significant correlation between the progression of physical and cognitive dysfunction.

Adolescent

Cognitive functioning and posttraumatic stress disorder.

OBJECTIVE: The authors examined the association of cognitive impairment with posttraumatic stress disorder (PTSD) and other psychiatric diagnoses known to affect cognitive functioning. METHOD: The results of standardized neuropsychological tests were compared in four groups of Vietnam veterans: veterans with both a lifetime history of PTSD and a current diagnosis of depression, anxiety, or substance abuse; veterans with only a PTSD diagnosis; veterans with only a current diagnosis of depression, anxiety, or substance abuse; and veterans with none of these diagnoses. RESULTS: Veterans with both PTSD and concurrent diagnoses. exhibited more impairment in cognitive functioning than did veterans without these diagnoses. CONCLUSIONS: Cognitive deficits seen among persons diagnosed with PTSD may be associated with their concomitant diagnoses.

Adult

Acute hyperglycaemia impairs cognitive function in children with IDDM.

OBJECTIVE: The effects of acute hyperglycaemia on cognitive function in children remain controversial. This study was designed to investigate the suggestion that acute hyperglycaemia impairs cognition in IDDM children. DESIGN: To examine this question we studied 12 randomly selected children with IDDM (6 boys, 6 girls, mean age 12.4 years). Cognitive performance was assessed on two occasions at least six months apart (7.4 +/- 1.4 mths, range: 6.3-11.1 mths) under randomised conditions of hyperglycaemia (20-30 mmol/l) on one occasion and euglycaemia (5-10 mmol/l) on the other. Target glucose levels were achieved using a modified clamp technique with subjects and psychologist blinded to the glycaemic level. Cognitive tests chosen to assess performance skills were subtests from the Wechsler Intelligence Scale for Children-3rd Edition (WISC-111). RESULTS: No significant learning effect was present. However, there was a reduction in performance IQ at hyperglycaemia compared with euglycaemia (106 +/- 4.3 vs 112 +/- 4.5 IQ points respectively, p < 0.05). Under hyperglycaemic conditions the mean decrease in percentile score for performance IQ was 9.5%. Of the 12 children tested, 8 had a decrease in IQ when hyperglycaemic, which was independent of duration of diabetes and long term metabolic control assessed by HbA1c. CONCLUSION: Acute hyperglycaemia results in impairment of complex cognitive function in children with IDDM. This may have important implications for school performance.

Adolescent

A prospective study of dehydroepiandrosterone sulfate and cognitive function in an older population: the Rancho Bernardo Study.

OBJECTIVE: To determine whether low plasma dehydroepiandrosterone sulfate (DHEAS) levels predict poor cognitive function in the elderly. DESIGN: A prospective, population-based study with periodic clinical evaluations and 100% follow-up for vital status. SETTING: Rancho Bernardo, California PATIENTS: 270 men and 167 women (80% of surviving, local, age-eligible subjects) from the Rancho Bernardo cohort who had plasma obtained for DHEAS assays in 1972 to 1974 and screening for dementia in 1988 to 1991. MEASUREMENTS: DHEAS levels were measured by radioimmunoassay. There were five interviewer-administered standard screening tests of cognitive function: Mini-Mental Status Examination, Buschke selective reminding test, Trails B, category fluency, and Heaton Visual Reproduction test. RESULTS: DHEAS levels were higher in men than women and decreased with age in both sexes. There were no significant differences in age-adjusted DHEAS levels in the percent of men or women with categorically impaired performance on any test. When analyzed as a continuous variable, DHEAS levels were significantly correlated with only one test, the Bushke, and only in women. Low baseline DHEAS levels were not associated with any mention of dementia on death certificates or with non-participation of survivors. Low levels of DHEAS predicted mortality in men more than in women such that men were more likely to have died before cognitive function testing than women. CONCLUSION: The single DHEAS-memory association, restricted to women, is most likely to be spurious, consequent to multiple comparisons. We cannot exclude a true effect of low DHEAS, restricted to women and reflecting their better survival than men.

Age Factors

Anticonvulsant drugs, cognitive function, and behavior.

Healthy volunteers as well as patients with epilepsy were studied for 2 weeks in a double-blind crossover design to determine the effect of anticonvulsant drugs on cognitive function and behavior. The healthy volunteers experienced significant deficits in performance with the four drugs examined, phenytoin, carbamazepine, sodium valproate, and clobazam. The most widespread changes were seen with phenytoin; carbamazepine, sodium valproate, and clobazam did not interfere with tests of memory function. The results of the patients' studies showed that (1) when anticonvulsants are reduced, patients receiving polytherapy improve their cognitive function; (2) patients with high serum levels of anticonvulsant drugs demonstrated more cognitive impairment than those with low levels; (3) when carbamazepine is substituted for another anticonvulsant, cognitive function is improved; and (4) in patients receiving monotherapy, high serum levels are linked to greater cognitive impairment than lower levels and the profile of changes differs between the drugs.

Anticonvulsants

Issues in the assessment of cognitive function in dementia.

The increasing prevalence of elderly patients presenting with disorders of cognitive functioning suggestive of dementia, coupled with limits in resources available to address these problems, is going to necessitate the development of new technologies to be used for assessment. These measures should be efficient, designed to reflect both the current knowledge of brain function and the developmental characteristics of older patients. Though few current measures of cognitive function meet these goals, neuropsychological "microbatteries" such as the DRS and NCSE may serve as models for a new generation of cognitively specific assessment instruments.

Aged

The impact of long-term vitamin supplementation on cognitive functioning.

The possibility that the taking of vitamin supplements may influence cognitive functioning was explored. One hundred and twenty-seven young healthy adults took either ten times the recommended daily dose of nine vitamins, or a placebo, under a double-blind procedure, for a year. After 12 months better performance on two measures of attention was found in females who had taken the vitamin supplement, even though the blood status of nine vitamins reached a plateau after 3 months. The use of regression equations demonstrated the association between improved thiamin status and improved performance on a range of measures of cognitive functioning in females rather than males. Although it was not possible to establish the reason for a beneficial response in females rather than males, the evidence that females respond differently to dietary factors was discussed.

Adolescent

The importance of comparative studies and ecological validity for understanding hippocampal structure and cognitive function.

Building from the premise that hippocampal cognitive function has been molded by natural selection under natural environmental conditions, it is argued that traditional laboratory studies likely do not reveal the richness and complexity of hippocampal function. Research on the role of the hippocampal formation in the navigational behavior of homing pigeons is offered as an example to illustrate the advantages of using an ecological approach to understand hippocampal function. It is further proposed that dissimilarities in hippocampal anatomy, physiology, and neurochemistry found between species reflect species differences in the range of functions served by the hippocampal formation, as well as possibly the molecular and cellular mechanisms that support such functions. These differences notwithstanding, it is suggested that, from an evolutionary perspective, the primary function of the hippocampal formation is a role in some aspect of spatial cognition. Dissimilarities in hippocampal structure and function among extant species are viewed as resulting from differences in evolutionary selective pressure and evolutionary history.

Animals

Withdrawal of antiepileptic medication in children--effects on cognitive function: The Multicenter Holmfrid Study.

We present 100 children diagnosed with epilepsy who were seizure-free for more than 1 year and still on monotherapy of antiepileptic drugs (AEDs). We matched each child with a healthy classmate and performed neuropsychological testing and EEG before and after complete withdrawal of the AEDs. The withdrawal phase lasted 3 months, but the dose decrease was individualized for each patient. Three to 4 months after complete withdrawal of the drug all patients were reassessed. Patients with seizure relapse are excluded from the study. Seventeen patients are regarded as dropout, 11 because of seizure relapse and six because of protocol violation. The remaining 83 patients were treated with carbamazepine (n = 56), valproic acid (n = 17), or phenytoin (n = 10). Serum concentrations of the AEDs were measured using peak plasma levels that were taken immediately before or after psychological testing. We used neuropsychological tests to assess psychomotor function and "central" cognitive processing such as information processing or memory function. We found significant improvement attributable to drug withdrawal on only one of the cognitive tests, namely, psychomotor speed, suggesting that the impact of AED treatment on higher-order cognitive function is rather limited. In addition, we found group differences between the epilepsy group and the control group at baseline that persisted after drug withdrawal. Subsequent analysis showed some factors that may have contributed to these group differences. First, patients with a former diagnosis of absence seizures show lower scores both at baseline and after drug withdrawal. We may assume that the seizure propensity has not disappeared completely in these patients. Some evidence is found that phenytoin may have a different cognitive profile than carbamazepine, with more impairment on tests that measure motor and mental speed. Again, this impairment persists after drug withdrawal.

Adolescent

Growth in utero and cognitive function in adult life: follow up study of people born between 1920 and 1943.

OBJECTIVES: To examine the relation between fetal growth and cognitive function in adult life. DESIGN: A follow up study of men and women whose birth weights and other measurements of body size had been recorded at birth. SETTING: Hertfordshire, Preston, and Sheffield. SUBJECTS: 1576 men and women born in Hertfordshire, Sheffield, or Preston between 1920 and 1943. MAIN OUTCOME MEASURES: Intelligence quotient as measured by the AH4 test and amount of decline in cognitive function with age as estimated by the difference between score on the Mill Hill vocabulary test and score on the AH4 test. RESULTS: Score on the intelligence test was higher in people who had a large biparietal head diameter at birth, but it was not related to any other measure of body size or proportions. No association was found between decline in cognitive function and any measure of size or proportions at birth. CONCLUSION: Impaired fetal growth was not associated with poorer cognitive performance in adult life. Adaptations made by the fetus in response to conditions that retard its growth seem to be largely successful in maintaining brain development.

Adult

Effect of valproate on cognitive functioning. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group.

OBJECTIVE: To assess the effects of carbamazepine vs valproate sodium on cognitive functioning in patients with epilepsy compared with normal control subjects. DESIGN: Patients with recently diagnosed, previously unmedicated seizures participated in a prospective randomized double-blind Department of Veterans Affairs multicenter study of the efficacy and toxicity of carbamazepine vs valproate. MAIN OUTCOME MEASURE: A behavioral toxicity battery was administered prior to treatment and again 6 and 12 months after the initiation of antiepileptic medication. RESULTS: There were no significant differences in the effect of carbamazepine vs valproate on motor speed and coordination, memory, or concentration and mental flexibility, and there was no significant decline in neuropsychological performance from pretreatment baseline levels for either drug. No significant differences in performance were found between patients with low (mean, 52.8 micrograms/mL) vs high (mean, 94.4 micrograms/mL) serum valproate levels within the therapeutic range. Patients treated with either carbamazepine or valproate did not show practice effects experienced by normal controls, a finding that may reflect a subtle compromise in cognitive functioning. CONCLUSION: The impact of carbamazepine and valproate monotherapy on cognitive functioning is similar: both drugs produce minimal negative effects compared with pretreatment baseline performance.

Adult

Cognitive functioning and the incidence of limitations in activities of daily living in an elderly community sample.

Although it is well-known that cognitive impairment in the elderly is usually accompanied by limitations in activities of daily living (ADL), it is not known whether cognitive impairment predicts the onset of new ADL limitations. The purpose of this analysis was to determine whether poor scores on a brief measure of cognitive functioning at baseline (1982) would predict the onset of persistent limitations in ADL during the subsequent 3 years, in a probability sample of community-dwelling elderly persons living in New Haven, Connecticut, who were initially free of ADL limitations (n = 1,856). Cognitive functioning was assessed with Pfeiffer's Short Portable Mental Status Questionnaire. Persistent incident ADL limitations were defined as the onset of one or more ADL limitations after 1982, with no subsequent reports of zero ADL limitations. Compared with persons who scored zero to one errors on the Short Portable Mental Status Questionnaire at baseline, persistent, incident ADL limitations occurred more frequently in persons who scored four or more errors (odds ratio for males = 2.72, 95% confidence interval 1.36-5.43; odds ratio for females = 2.60, 95% confidence interval 1.52-4.44) after adjustment for the confounding effects of housing type, age, race, history of chronic health conditions, and incident health conditions. These results suggest that knowledge of scores on brief cognitive function tests can be used to forecast service needs and to develop intervention programs to prepare for the possible onset of ADL limitations.

Activities of Daily Living

Effects of night work on the cognitive function in young and elderly subjects with specific reference to the auditory P300.

To estimate the effects of night work on the human cognitive function, P300 event related potentials (ERPs) evoked with an auditory "oddball" paradigm were recorded for 17 nurses (mean age 27.4 +/- 6.1 years; range 21-41 years) for 3 epochs; after a night of work, after a day of work and on a holiday, and for 12 elderly security guards (mean age 62.8 +/- 2.2 years; range 60-67 years) for 2 epochs; after a night of work and on a holiday. The Stress Arousal Check List (SACL) was used for all the subjects just prior to the P300 ERP recording to determine the extent of stress and the arousal grades. Fourteen of the nurses were in their twenties (mean age 24.9 +/- 2.6 years; range 21-29 years), and 3 (39.0 +/- 2.6) were older (36, 40 and 41 years). The 14 nurses were classed as the young group. All the security guards were classed as the elderly group. In the young group, the stress grade scores increased significantly (P < 0.05) and the arousal grades decreased significantly (P < 0.01) after night work as compared to the holiday values. Although statistically not significant, the amplitude of the P300 component tended to decrease after night work, whereas the latency was very stable for these 2 epochs. The P300 latencies of the 3 older nurses were as stable as those of the young group, but their amplitudes were significantly reduced after night work as compared with the holiday amplitudes (P < 0.05). In contrast, the 12 elderly security guards showed no statistically significant changes in the scores for the stress and arousal grades between the 2 epochs, after night work and holiday. Latency prolongation however, was statistically significant (P < 0.01) after night work. The P300 amplitudes for many of the elderly security guards also tended to decrease after night work, but were not statistically significant. The P300 amplitude is considered to reflect the amount of attentional resources and the latency to reflect the time needed for the cognitive process, indicating that the elderly security guards experiences slowing of the cognitive process in night work. Our results suggest that the effect of night work on the cognitive function is greater for elderly than for young workers. We conclude that P300 can be used to evaluate changes in the human cognitive function produced by night or rotating shift work and that the results provide useful information with which to plan shift schedules on the basis of worker age.

Adult

[Diffuse bilateral periventricular hyperintensity of unknown origin on MRI spin-echo sequence. Cognitive function and regional cerebral blood flow].

Cognitive function and regional cerebral blood flow (rCBF) were studied in 26 patients (mean age 77.9) who showed bilaterally an ill-defined diffuse periventricular hyperintensity (PVH) on the magnetic resonance imaging (MRI) spin-echo sequence. Diffuse PVH was classified into two groups according to severity, group A (more severe) and group B (less severe); their cognitive impairment was classified into three stages, stage 1 (mildly impaired) through stage 3 (severely impaired). rCBF was assessed by single photon emission computed tomography (SPECT). The result showed that 6 of 7 MRI-group A patients were stage 3, but the stages of 19 group B patients varied. Five of 7 MRI-group A patients showed severe hypoperfusion, but rCBF of group B patients also varied. Nineteen patients had a hypertensive history, but only 10 patients complained of cerebrovascular incidents before admission. All 3 younger patients (one in his fifties and two in their sixties), however, showed hypertension, stepwise neurological deterioration as in Binswanger's disease. These results suggest that there might be various pathogenesis of diffuse bilateral PVH in the elderly and they are different from that of the classical "Binswanger's disease".

Aged