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PubMed2004

Preserved cognitive function after 12 months of treatment with rivastigmine in mild Alzheimer's disease in comparison with untreated AD and MCI patients.

Cholinesterase inhibitors (ChEIs) have shown positive symptomatic effects on cognition, activities of daily living, and behavior in patients with Alzheimer's disease (AD). Rivastigmine is a slowly reversible ChEI that inhibits acetylcholinesterase and butyrylcholinesterase. We evaluated the effects of long-term rivastigmine treatment on cognitive function and plasma levels of ChE activity, and the relationship between ChE activity and cognition. Patients with mild AD (n = 11) treated with rivastigmine for 12 months were compared with matched groups of untreated patients with AD (n = 21) or mild cognitive impairment (MCI; n = 22) representing the natural course of the pre-clinical and very early stage of disease. For untreated AD patients, neuropsychological assessment was made at baseline and 12 months. Determination of ChE activity in plasma and assessment of global cognition, episodic memory, visuospatial ability, and attention were performed at 0 (baseline), 3, 6, and 12 months for treated AD patients and untreated MCI patients. At 12 months, cognitive function was slightly improved or maintained in mild AD patients treated with rivastigmine. In contrast, cognition was markedly worsened in untreated AD patients and unchanged or slightly worsened in untreated MCI patients. In the group of treated AD patients, there was a significant correlation between plasma ChE inhibition and cognition, particularly in relation to attention. This effect was most apparent at 3 months of treatment. In conclusion, a clear beneficial effect of rivastigmine was shown on cognitive function for patients with mild AD and plasma values of ChE inhibition were associated with attention.

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PubMedDate not supplied

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↗

PubMed2001

Duration of untreated psychosis and cognitive functioning in first-episode patients.

BACKGROUND: The "toxicity" model of duration of untreated psychosis (DUP) suggests that longer DUP will be associated with poorer performance on cognitive tests in first-episode patients. AIMS: To test this hypothesis on a sample of 113 patients in a community-based early intervention programme for psychosis. METHOD: Information was collected concerning a number of possible predictors of cognitive functioning including DUP. These were examined for their relation to performance on an extensive battery of cognitive tests administered shortly after the patients' admission to the programme. RESULTS: Although several variables such as gender, premorbid adjustment, education and handedness predicted cognitive functioning, no relation was found between DUP and performance on any component of the test battery. CONCLUSIONS: Findings do not provide support for a toxic effect of DUP on cognitive functioning. Other mechanisms through which DUP might affect outcome such as psychological engulfment, social support and adherence to medication are discussed.

Adolescent↗

PubMedDate not supplied

[The effect of rivastigmine on cognitive functions and regional cerebral blood flow in Alzheimer's disease and vascular dementia: follow-up for 2 years].

BACKGROUND AND PURPOSE: The aim of the work was to investigate the effect of treatment with rivastigmine, one of the inhibitors of acetylcholinesterase (AChE-I) on the regional cerebral perfusion (rCBF) and the cognitive functions of the brain in patients with Alzheimer's Disease (AD) and Vascular Dementia (VaD). MATERIAL AND METHODS: The investigations of rCBF were carried out using SPECT (Single Photon Emission Computed Tomography). The results given concern investigations of patients carried out at the onset of the investigation, after 12 months, and 24 months of rivastigmine treatment. RESULTS: In patients with AD it was found that treatment with rivastigmine increases rCBF by 5-7% in the temporal areas during the first 12 months. In the frontal areas the increase was by 3-5%. During the next 12 months rCBF with an accuracy of 2% returned to the initial level, with the exception of the motor cortex, where it remained on the level increased by 5-6%. However, the cognitive functions remained constant during the first 12 months of treatment and decreased significantly during the next 12 months. In patients with VaD rCBF increased in all the regions of the brain except for the temporal posterior regions, and remained at an elevated level for the next 12 months. The cognitive functions deteriorated slowly, but to a much lesser degree than in the case of AD. CONCLUSIONS: From the investigations carried out it follows that treatment with rivastigmine during 24 months prevents a decrease of rCBF in patients with AD. However, the cognitive functions deteriorate after 24 months.

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PubMed2000

Nithsdale Schizophrenia Surveys. 20. Cognitive function in a catchment-area-based population of patients with schizophrenia.

BACKGROUND: Cognitive deficits are a core aspect of schizophrenia but there has been no study of cognitive function in a catchment-area-based population of patients with schizophrenia. AIMS: To assess cognitive function in a population of patients with schizophrenia, and relate it to community functioning. METHOD: All patients with schizophrenia in Nithsdale, south-west Scotland, were identified (n = 182). Measures of assessment were: National Adult Reading Test (NART), Mini-Mental State Examination (MMSE), Rivermead Behavioural Memory Test (RBMT), Executive Interview (EXIT), FAS Verbal Fluency and Health of the Nation Outcome Scales (HoNOS). RESULTS: We assessed 138 patients, mean age 48 years (standard deviation (s.d.) 15). Only 14% were in-patients. The mean premorbid IQ as assessed by NART was 98 (s.d. 14); 15% of patients had significant global cognitive impairment (MMSE); 81% had impaired memory (RBMT); 25% had executive dyscontrol (EXIT); and 49% had impaired verbal fluency (FAS). Scores on the functional impairment sub-scale of HoNOS correlated with all measures of cognitive impairment. CONCLUSIONS: Cognitive dysfunction is pervasive in a community-based population of patients with schizophrenia.

Adult↗

PubMed1994

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↗

PubMed1983

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↗

PubMed2002

Detecting residual cognitive function in persistent vegetative state.

Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H(2)(15)O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.

Adult↗

PubMed1996

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.

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PubMed1995

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↗

PubMed1992

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↗

PubMed2003

The influence of risperidone on cognitive functions in schizophrenia.

Introduction of the antipsychotics of the second generation (SGA) into the therapy of schizophrenia roused expectations that, finally, the cognitive dysfunction in schizophrenia could be eliminated by psychopharmacological therapy. The purpose of the study was to verify the effect of atypical antipsychotic risperidone on cognitive functions in schizophrenic patients. The study was carried out upon 48 male schizophrenic patients aged 21-47 years who were switched from the antipsychotics of the first generation (FGA) to the antipsychotic risperidone, due to intolerance, during the treatment. Intelligence, abstract and concrete thinking and mental speed, attention, and short-term non-verbal memory prior to the switch, one month after the switch, and three months after the switch to risperidone, were evaluated. One month after the switch the number of subjects with severe impairment of intellectual abilities decreased significantly from 62% to 15% and after three months the number was even lower-8%. The impairment of concrete and abstract thinking and mental speed also showed the same tendencies of decrease. The improvement of the cognitive functioning after the switch from the antipsychotics of the first generation to the antipsychotic risperidone is explained by removal of the antipsychotics of the first generation from the therapy and the consequential disinhibition of secondary cognitive impairments and by decreased average dose of anticholinergic and decreased number of patients who need anticholinergic therapy beside risperidone. The possibility of clear pro-cognitive effect of risperidone is suggested and its verification is proposed with strict control of other factors that improve cognitive functioning of schizophrenic patients during the treatment.

Adult↗

PubMed2000

Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen.

BACKGROUND: Tamoxifen is an anti-estrogen used in the treatment of breast cancer and to reduce the incidence of breast cancer in high risk women. Although the brain is an estrogen target organ and several studies have found a beneficial effect of estrogen on cognitive function, the effect of tamoxifen on cognition has not been reported. Therefore, we initiated a follow-up study of women who had participated in a study of breast cancer to assess the effect of tamoxifen treatment on cognitive function. METHODS: We recruited previously interviewed patients who were cases in a population-based case-control study of 2,653 women with primary breast cancer diagnosed between 1987 and 1996 at ages 55-72 years in Los Angeles County, California, USA. In November 1997, each case was mailed a follow-up questionnaire. Cognitive function was assessed by (1) clock drawing. (2) copying a box drawing, and (3) narrative writing to describe a pictured scene. Women reporting treatment with tamoxifen were categorized as standard-term users (4-5 years), short-term users (< 4 years) or long-term users (6 + years) and compared to never users. Tamoxifen users were also classified as past or current users. Differences in the mean cognitive test scores were tested after adjusting for age, age at diagnosis, stage of disease, radiation therapy, chemotherapy, race, education, marital status, previous use of oral contraceptives, type of menopause, age at last menstrual period, previous use of hormone replacement therapy, and depressive symptoms using analysis of covariance. All p-values for differences in the proportion of women who had errors on the tests are 2-sided and adjusted for age, stage of disease at diagnosis, and chemotherapy. FINDINGS: Information from 1,163 women aged 57-75 years of age was analyzed; 710 had taken tamoxifen. There was little difference between women who had used tamoxifen for the standard five years and never users on the three cognitive tests. However, more women who had used tamoxifen for the standard term reported seeing their physician for memory problems than non-users (3.8% vs 1.5%, p = 0.04). This was especially true for current users of standard-term (8.0%, p = 0.003). Current users also had a significantly lower mean complexity score (p = 0.03) on the narrative writing task. No differences were seen between past users and non-users. INTERPRETATION: Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment.

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PubMed2000

Incidence of stroke in relation to cognitive function and dementia in the Kungsholmen Project.

OBJECTIVE: To investigate whether cognitive function is related to incidence of stroke. METHODS: A population-based cohort of 1551 subjects with no clinical history or signs of stroke, age 75 years and over at baseline, were followed up for 3 years. Individuals with a first-ever stroke event that was recorded in the Stockholm inpatient register after the date of baseline interview were considered as incident stroke patients. Diagnosis of stroke followed the International Classification of Disease, 9th Revision (ICD-9). Diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised (DSM-III-R). Cognitive functioning was assessed with the Mini-Mental State Examination. RESULTS: During the 4102 person-years of follow-up, 110 events were recorded, giving an overall incidence of stroke of 26.8 per 1000 person-years. Subjects with mild dementia had a relative risk of 2.6 (95% CI, 1.2 to 5.7) of developing stroke after controlling for the potential confounders. The corresponding figure for subjects with cognitive impairment was 2.0 (95% CI, 1.0 to 3.8; p = 0.05). There was a tendency for subjects who developed stroke to be more likely to have vascular factors (systolic blood pressure >180 mm Hg, heart disease, or diabetes mellitus) than those who did not. CONCLUSIONS: Mild dementia and cognitive impairment are associated with an increased incidence of stroke among subjects age 75 years old and over. Because stroke increases risk of dementia and prior stroke increases risk of a subsequent stroke, mild dementia and cognitive impairment may be a manifestation of clinically unrecognized stroke.

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PubMed2002

Birthweight, postnatal growth and cognitive function in a national UK birth cohort.

BACKGROUND: Birthweight is associated with cognition and educational attainment across the full birthweight range in the normal population, independently of social background. However, the extent to which birthweight reflects fetal growth, or is a marker of subsequent size, with respect to this association, is not clear. We therefore investigated the independent effects of birthweight and postnatal height adjusted for postnatal weight on cognitive function and educational attainment while controlling for family background. METHODS: Using the British 1946 birth cohort we investigated the association between cognitive function at various ages and birthweight, height adjusted for weight in childhood and adulthood, and educational attainment, controlling for sex, father's social class, maternal education, birth order, and maternal age. RESULTS: Birthweight was positively associated with cognition up to age 26, and with the likelihood of obtaining advanced educational qualifications. Height was positively associated with cognition at all ages, and also with educational attainment. Weight was not associated with cognition at ages 8 and 15, but was negatively associated with verbal ability at age 26, with verbal memory at age 43, and with educational attainment. These effects were independent of each other, and of family background. Conditional analyses suggested the positive effect of height growth on cognition at two intervals, one in early childhood, and the other in late adolescence. In addition, weight gain after age 15 was negatively associated with cognition at 26. CONCLUSION: Birthweight and postnatal growth are independently associated with cognition.

Adult↗

PubMed1993

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↗

PubMed1996

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↗

PubMed1996

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.

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