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Neuropsychological performance in Alzheimer's disease and vascular dementia: comparisons in a memory clinic population.

OBJECTIVES: To compare the performances of two matched groups of patients with Alzheimer's disease (AD) and vascular dementia (VaD) on a battery of neuropsychological tests. METHODS: 325 patients attending a memory clinic were given a detailed multi-disciplinary diagnostic assessment, including a battery of neuropsychological tests administered by a psychologist and a speech and language therapist. The performances of two groups of patients meeting ICD-10 criteria for AD (n = 103) and VaD (n = 68) were compared, adjusting for age, gender, dementia severity and pre-morbid IQ. Patients with co-morbid depression and mixed AD+VaD were excluded. RESULTS: After adjustment, the AD and VaD groups differed significantly on the Graded Naming Test (VaD superior), AMIPB Complex Design immediate and delayed recall (VaD superior), the Trail Making Test error score (Part B) (VaD superior), and Verbal Picture Description (VaD superior). CONCLUSIONS: These findings support previous evidence that language function and non-verbal memory are selectively more impaired in AD. The better performance by VaD patients on the Trail Making Test (B) runs counter to previous suggestions that there is an excess of frontal executive dysfunction in this disorder. It may be that this test is more sensitive to the early impairment of concurrent manipulation of information in AD.

Aged↗

Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's trial of hypertension in older adults.

OBJECTIVE: To establish whether initiation of treatment with diuretic or beta blocker is associated over 54 months with change in cognitive function. DESIGN: A cognitive substudy, nested within a randomised, placebo controlled, single blind trial. SETTING: 226 general practices from the Medical Research Council's general practice research framework. SUBJECTS: A subset of 2584 subjects sequentially recruited from among the 4396 participants aged 65-74 in the trial of treatment of hypertension in older adults. The 4396 subjects were randomised to receive diuretic, beta blocker, or placebo. Subjects had mean systolic pressures of 160-209 mm Hg and mean diastolic pressures <115 mm Hg during an eight week run in. OUTCOME MEASURES: The rate of change in paired associate learning test (PALT) and trail making test part A (TMT) scores (administered at entry and at 1, 9, 21, and 54 months) over time. RESULTS: There was no difference in the mean learning test coefficients (rate of change of score over time) between the three treatments: diuretic -0.31 (95% confidence interval -0.23 to -0.39), beta blocker -0.33 (-0.25 to -0.41), placebo -0.30, (-0.24 to -0.36). There was also no difference in the mean trail making coefficients (rate of change in time taken to complete over time) between the three groups: diuretic -2.73 (95% confidence interval -3.57 to -1.88), beta blocker -2.08 (-3.29 to -0.87), placebo -3.01, (-3.69 to -2.32). A less conservative protocol analysis confirmed this negative finding. CONCLUSION: Treating moderate hypertension in older people is unlikely to influence, for better or for worse, subsequent cognitive function.

Adrenergic beta-Antagonists↗

Familial, obstetric, and other clinical correlates of minor physical anomalies in schizophrenia.

OBJECTIVE: This study investigated possible antecedents of minor physical anomalies in schizophrenia, particularly in terms of obstetric and genetic factors, and demographic, clinical and cognitive correlates of such anomalies in schizophrenia. METHOD: Forty-one outpatients satisfying the DSM-III criteria for schizophrenia were examined for minor physical anomalies by using the Waldrop scale. These subjects were drawn from a group of 45 such patients whose cognitive function had been previously evaluated with Trail Making Tests A and B and whose biological mothers had been interviewed for any history of obstetric complications or family history of schizophrenia. RESULTS: Linear multiple regression analysis showed that higher scores for minor physical anomalies were associated with impaired cognitive flexibility on Trail Making Test B, family history of schizophrenia in a first-degree relative, maternal history of obstetric complications, smaller number of siblings, later position in the birth order, and male sex. A family history of schizophrenia was particularly associated with abnormalities of the mouth. The association between minor physical anomalies in the patients and obstetric complications in their mothers appeared to be confined to instances in which the mother had a history of bleeding in early pregnancy. CONCLUSIONS: Minor physical anomalies indicate early dysmorphogenesis in schizophrenia, particularly in males, which appears to be associated more reliably with genetic rather than obstetric factors and with cognitive impairment.

Adult↗

Tests of executive function predict instrumental activities of daily living in community-dwelling older individuals.

The purpose of this study was to examine the utility of specific tests of executive functioning for predicting instrumental activities of daily living (IADLs) in community-dwelling older individuals (n = 30). In addition to tests of frontal and executive functioning, performance-based and caregiver-rated evaluations of IADLs were obtained. Results indicated that different tests of executive functioning were associated with outcomes on performance-based versus caregiver-rated assessments of IADLs. Specifically, the Trail Making Test (Part B) made a significant and unique contribution to the prediction of performance-based IADLs. In contrast, verbal fluency performance and Trail Making Test performance made significant independent contributions to the prediction of IADLs as reported by a caregiver. These findings suggest that different aspects of frontal and executive functions may be related to IADLs, depending on the type of assessment instrument used. Key words: activities of daily living, executive function, older adults

Activities of Daily Living↗

Sparing of cognitive function in mild hypoglycemia: dissociation from the neuroendocrine response.

Central nervous system function during insulin-induced reductions in plasma glucose was studied by measuring plasma epinephrine concentrations and testing cognitive function. Mild glucose reduction [mean plasma glucose, 62 +/- 3 (+/- SEM) mg/dL (3.4 +/- 0.2 mmol/L)] was induced with an iv insulin infusion at the rate of 40 mU/kg.h for 180 min in 7 normal subjects. Despite a marked increase in mean plasma epinephrine concentrations, which peaked at 426 +/- 68 pm/mL (2325 +/- 371 pmol/mL; P less than 0.001), no significant differences in cognitive function occurred as determined by a series of trail-making tests compared with the results of serial tests in a group of 17 control subjects. In contrast, when hypoglycemia was induced (plasma glucose, less than 42 mg/dL; 2.3 mmol/L) by bolus injection of insulin in 4 normal subjects, cognitive function was impaired in every subject, as demonstrated by a delay in completion of the trail-making test. The mean completion time was prolonged to 107 +/- 16% of the baseline at the time of hypoglycemia vs. 74 +/- 4% in control subjects (P less than 0.01). These findings suggest that cognitive function may be spared during mild plasma glucose reductions and is dissociated from the neuroendocrine adrenergic response that is activated under these conditions. This dissociation may be part of a homeostatic process in which overall brain function is maintained during glucoprivation, although counterregulation has already been triggered to prevent a further decrease in plasma glucose.

Adult↗

The development and evaluation of a clinical test of surgical resident proficiency.

The two purposes of this study were to develop a clinical test of surgical resident proficiency and to compare this clinical test with currently applied methods of resident evaluation. Appendicitis is a common surgical disease, and its accurate diagnosis depends largely on clinical acumen. Ten third-year surgical residents prospectively evaluated 107 patients admitted because of suspected appendicitis. After taking a history, performing a physical examination, and reviewing laboratory data, these residents were asked to state, as a percentage, the likelihood that each patient had appendicitis. Sixty-three patients had appendicitis documented by pathologic inspection after appendectomy. Forty-four patients did not have appendicitis, as was determined by operation (17) or by in-house observation and resolution of abdominal pain (27). These outcomes were used to calculate a diagnostic ability score (DAS) for each resident. Residents were evaluated by standard methods including in-service examinations and monthly evaluations by the attending staff. Residents were also evaluated by nonstandard, but potentially useful, neuropsychologic and psychologic tests, including the trail making test, the Ravens progressive matrices test, the paced auditory serial addition test (PASAT), the grooved pegboard test of manual dexterity, and the profile of mood states (POMS) psychologic questionnaire. Cumulative scores were calculated and compared by multiple regression with coefficient variance analysis. The correlation (R2) of DAS with standard evaluation techniques was as follows: In-service (0.055), faculty (0.508), trails (-0.293), Ravens (0.028), PASAT (0.251), dexterity (0.432), POMS (0.381). We found that (1) the DAS is a discriminating clinical test; (2) the DAS correlates with subjective faculty evaluation; and (3) the DAS does not correlate with in-service examination scores. We conclude that faculty evaluation remains the best currently applied test of surgical resident clinical proficiency as measured by the DAS.

Adult↗

Quantitative evaluation of age-related white matter microstructural changes on MRI by multifractal analysis.

Multifractal analysis has been applied to evaluate biological tissues, which are composed of complex structures. We carried out multifractal analyses in a group of healthy young and elderly subjects to examine age-related white matter microstructural changes on T2-weighted MR images without any visible abnormal intensity, and to correlate such changes with age-related cognitive decline. Comparison between the two age groups showed that Deltaalpha (established as the most suitable index of heterogeneity in our previous report) in the frontal region was significantly higher in the elderly group, but no significant group difference was found in Deltaalpha in the parieto-occipital region. The Trail-Making Test score (a measure of executive dysfunction) was significantly higher in the elderly group. In the elderly group, the Trail-Making Test score was positively correlated with Deltaalpha in the frontal region, but not in the parieto-occipital region. These results suggest that microstructural changes in the white matter preferentially occur in the frontal region with normal aging, and these changes are associated with executive cognitive decline reflective of frontal-subcortical dysfunction.

Adult↗

An empiric approach to level of care determinations: the importance of executive measures.

BACKGROUND: The ability to predict the level of care received by elderly retirees was compared in a discriminant model and using a classification tree derived from cognitive and noncognitive variables. Methods. Participants were 193 residents (mean age, 79.1+/-5.1 years) of a single, 1,500-bed, continuing care retirement community. They were given a battery of cognitive measures that included tests of general cognition, memory, and executive control function. A multivariate discriminant model of level of care was compared with a classification tree. RESULTS: Residents in congregate high-rises (n=115) differed significantly from those in apartment settings (n=78) with respect to age, Executive Interview (EXIT 25), and the Executive Clock-Drawing Task (CLOX). Only age and executive control function measures (CLOX1, EXIT 25, and Trail Making Test Part B [Trails B]) contributed independently to a discriminant model of level of care (Wilke's lambda=0.92; F [df 4,170]=3.48; p <.01). Sixty-three percent of participants were correctly classified. A classification tree derived from the same variable set was more accurate (75% correctly classified). Age, CLOX1, and EXIT 25 made the most important contributions to the model. The EXIT 25 and CLOX1 thresholds empirically derived from this model coincide with the fifth percentiles for these instruments in a young adult sample. CONCLUSIONS: Executive control function appears to be most responsible for the effect of cognition on level of care. Young adult norms may be most relevant when the effects of cognitive impairment on functional status are assessed.

Activities of Daily Living↗

Effects of sleep deprivation on performance of Naval seamen: I. Total sleep deprivation on performance.

Sleep deprivation leads to impairment in performance, loss of efficiency and deterioration in mood states such as tension, depression, aggression, fatigue, confusion and vigour. These can be detrimental to combat readiness and could contribute to "battle stress". In the present study, a homogeneous group of 20 seamen under total sleep deprivation was rated 6 hourly with the Stanford Sleepiness Scale (SSS), Profile of Mood States (POMS) and a battery of performance tests including the trail making, grooved peg board, digit span, digit symbol, sea-shore rhythm, flicker fusion, dynamometer and naval tasks. With the exception of the trail making test and naval tasks, the test performance was observed to correlate significantly (P < 0.05) with the SSS. A higher sleepiness score was associated with a poorer performance in test scores. On the time trends of sleep deprivation on the performance tests measured, a dip in performance was observed in all the tests at 42 hours of sleep deprivation and continuous deterioration of performance was observed after 72 hours of sleep deprivation. The cognitive, vigilance, mood and sleepiness tests were substantially affected by sleep deprivation. Greater effect was observed in tests that involved cognition, speed and precision and smaller effect was observed in routine tasks that involved gross manual movement. The decrease in performance observed at 42 hours of sleep deprivation was 5.9 standard deviation from initial values for SSS; 3.9 for sea-shore rhythm, 3.0 for grooved peg board; 2.6 for dynamometer; 2.4 for mood; 1.8 for digit span; 1.6 for trail making and digit symbol; 1.0 for naval tasks and addition; and 0.9 for flicker fusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Endogenous sex hormones and cognitive function in older men.

The objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59-89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the "World" Backwards components, and the Trail-Making Test Part B. In age- and education-adjusted analyses, men with higher levels of total and bioavailable estradiol had poorer scores on the BIMC Test and Mini-Mental State Examination. Men with higher levels of bioavailable testosterone had better scores on the BIMC Test and the Selective Reminding Test (long-term storage). Five associations were U-shaped: total testosterone and total and bioavailable estradiol with the BIMC Test; bioavailable testosterone with the "World" test; and total estradiol with the Trail-Making Test. All associations were relatively weak but independent of age, education, body mass index, alcohol use, cigarette smoking and depression. In these older men, low estradiol and high testosterone levels predicted better performance on several tests of cognitive function. Linear and nonlinear associations were also found, suggesting that an optimal level of sex hormones may exist for some cognitive functions.

Aged↗

Smoking and schizophrenia: is symptom profile related to smoking and which antipsychotic medication is of benefit in reducing cigarette use?

OBJECTIVE: Smoking rate is disproportionately high among patients with schizophrenia, resulting in significant morbidity and mortality. However, cigarette smoking has been reported to have beneficial effects on negative symptoms, extrapyramidal symptoms, cognitive functioning and mood symptoms. Therefore, smoking cessation may worsen disability in schizophrenia. The association between smoking and these key clinical parameters was examined. Additionally, severity of smoking across four different antipsychotic treatment groups was explored. METHOD: One hundred and forty-six patients with schizophrenia were assessed for smoking using expired carbon monoxide and smoking history. They were administered the Positive and Negative Symptom Scale, The Extrapyramidal Symptom Rating Scale, the Barnes Akathisia Rating Scale, Reitans Trail-making Test (A and B) and General Health Questionnaire-28. RESULTS: There was no difference in the chlorpromazine equivalent dose of any of the medications studied. Atypical agents were associated with significantly lower levels of smoking when compared with typical medications. There was no difference in smoking severity between the individual atypical medications examined. Similarly, there were no significant differences between smoking and non-smoking groups with regard to Positive and Negative Symptom Scale, Extrapyramidal Symptom Rating Scale, Trail-making Test and General Health Questionnaire-28. However, there was a significant difference between these groups with the smoking group demonstrating less akathisia. CONCLUSIONS: Smoking is not associated with positive, negative cognitive and mood symptoms in schizophrenia. Smoking is associated with lower levels of antipsychotic induced akathisia. Clinicians should not be discouraged from helping patients stop smoking for fear of worsening symptoms. However, akathisia may emerge upon cessation of smoking. Switching patients from typical to atypical antipsychotics may assist patients with schizophrenia to give up smoking.

Adult↗

Construct validity of neuropsychological tests of conceptual and attentional abilities.

In a mixed sample of community-living adults, this study examined the construct validity of five neuropsychological tests: Category Test (CAT), Wisconsin Card Sorting Test (WCST), Paced Auditory Serial Addition Task (PASAT), Visual Search and Attention Test (VSAT) and Trail Making Test: Part B (TMT-B). Principal components analyses showed that PASAT, VSAT, and TMT-B defined an attention factor and that CAT and WCST defined a conceptual factor. The results were discussed in terms of common interpretations of these procedures as well as in terms of Mirsky's (1989) components of attention.

Adolescent↗

Comparative effects of risperidone and olanzapine on cognition in elderly patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder. METHOD: One hundred seventy-six elderly inpatients and outpatients with schizophrenia or schizoaffective disorder were enrolled in this multicenter, double-blind trial. After their antipsychotic medications were tapered for 1 week, patients were randomly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks. Performance on the Continuous Performance Test (CPT), Serial Verbal Learning Test (SVLT), TMT (Trail Making Test) Parts A and B, Wisconsin Card Sorting Test (WCST), and Verbal Fluency Examinations (VFE) was assessed at baseline and at end point. RESULTS: Patients in the risperidone group had improved scores on at least one test of attention, memory, executive function, and verbal fluency, and those in the olanzapine group had improved scores on at least one test of attention and memory function. Scores on the TMT Part B, WCST total errors (executive function domain), and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group. No significant differences in change scores between the two groups were found. Higher baseline scores on each test predicted more improvement at endpoint. CONCLUSIONS: Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder. Consistent with research in younger populations, these improvements occur in aspects of cognitive functioning related to functional outcome.

Aged↗

No identifiable effect of ginseng (Gericomplex) as an adjuvant in the treatment of geriatric patients.

This study aimed to examine the effect of ginseng as an adjuvant to treatment and rehabilitation of geriatric patients in a double blind, controlled clinical trial. The treatment group (N = 24) received two capsules of Gericomplex (ginseng, vitamins, minerals and trace elements) daily for 8 weeks, while the control group (N = 25) had identical-looking placebo capsules. Participants consisted of 60 geriatric patients, mean age 77.9 years. The principal study variables were length of stay in hospital, and activities of daily living according to the Barthel ADL Index. Cognitive function was assessed at baseline and after 8 weeks, using the Mini-Mental State Examination, the Kendrick Object Learning test, and the Trail Making test. Somatic symptoms, and symptoms of depression and anxiety were scored on a 23-question version of the Hopkins Symptom Checklist. Length of stay in hospital did not differ in the two groups, which also improved to the same degree on the various functional outcome measures, except for the Kendrick Object Learning test, where the placebo group improved more markedly. In conclusion, no identifiable effect of ginseng as an adjuvant to treatment and rehabilitation of geriatric patients was observed.

Adjuvants, Pharmaceutic↗

Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study.

OBJECTIVE: The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a randomized, double-blind trial. METHOD: Three hundred and seventy-seven patients were randomly assigned to receive 2-6 mg/day of risperidone or 5-20 mg/day of olanzapine for 8 weeks. Cognitive function was assessed with a focused cognitive assessment battery; in addition, extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale (ESRS), and the positive and negative syndrome scale (PANSS) was rated for all patients. RESULTS: Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test, the trail-making test, the California verbal learning test, the continuous performance test, and some aspects of verbal fluency and spatial working memory. No differences in the effects of the drugs on any of the cognitive tests were noted. Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects. CONCLUSIONS: Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning. Previous reports of greater benefits of olanzapine over risperidone in a small-sample pilot study were not substantiated. These results are not due in general to changes in clinical symptoms or movement disorders, suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia.

Adolescent↗

Frontal lobe-dependent functions in treated phenylketonuria: blood phenylalanine concentrations and long-term deficits in adolescents and young adults.

Even early-treated phenylketonurics may suffer from phenylalanine-related deficits. Elevated phenylalanine concentrations can interfere with the development and function of the CNS. Outcome beyond childhood has not been extensively investigated. This long-term study was performed to determine whether adolescents and young adults with PKU show frontal lobe-dependent deficits when compared to diabetic patients. The comparative study covered 35 PKU patients, 13-21 years of age (mean 17.8 years), and 35 diabetic patients matched for sex, age and socioeconomic status. Patients were assessed for IQ (Culture Fair Intelligence Test), information processing (Trail Making Test), and selective and sustained attention (Stroop Task, Test d-2). Assessments were repeated within a 3-year follow-up. PKU patients showed no increase in blood phenylalanine concentrations at follow-up. They had significantly poorer test results than the diabetic patients at both assessment times. Within the tests, however, this was due to reduced performance speed but not to deficits in specific frontal lobe-dependent functions. Elevated phenylalanine concentrations seem to exert a global effect slowing performance speed. This effect is enduring in adolescence and early adulthood.

Adolescent↗

Global cerebral blood flow in relation to cognitive performance and reserve in subjects with mild memory deficits.

PURPOSE: This study was undertaken to explore the mechanisms underlying cognitive reserve in subjects with mild memory deficits by using positron emission tomography (PET). METHODS: Global cerebral blood flow (gCBF) and cerebrovascular reserve (CVR) measurements were performed in 15 elders (5 men, 10 women, 62-84, 71.8 +/- 6.2 years) meeting criteria for mild cognitive impairment (MCI). PET consisted of quantitative [(15)O]water determinations of CBF, two at baseline and one postadministration of acetazolamide (ACZ). RESULTS: Mean gCBF were 44.9 +/- 5.5 during counting, 44.5 +/- 6.7 for the memory task, and 60.2 +/- 4.8 ml/min/100 g for post-ACZ (CVR of 33.9 +/- 13.2%). Task-related gCBF change was significantly related to memory score, performance on the Trail Making Test B (Trails-B), premorbid IQ, and education, and differed significantly between the learning-based groups. CONCLUSIONS: Cognitive reserve appears analogous to cardiac reserve. The ability to alter gCBF paralleled performance on general cognitive measures, was enhanced in higher levels of cognitive reserve, and was impaired in individuals who no longer appear to benefit from repeated exposure to testing.

Acetazolamide↗

Attention/information processing, neuropsychological functioning, and thought disorder during the acute and partial recovery phases of schizophrenia: a longitudinal study.

Schizophrenic subjects were administered the span of apprehension task, which is a measure of visual information processing; two neuropsychological tests; and measures of specific aspects of thought disorder and general clinical state. The measures were administered both when patients were acutely disturbed and when they were partially recovered. Normal control subjects were tested over a comparable 12-week interval. Improvements in both overall clinical condition and specific aspects of thought disorder occurred in the schizophrenic patients during this time. The patients, however, continued to show impaired information processing, indicating that the span of apprehension task is sensitive to schizophrenic dysfunction across wide variations in clinical state and, therefore, may be a marker of vulnerability to schizophrenia. The span of apprehension task was found to be significantly correlated with a measure of thought disorder that assesses resistance to associative distractors and two neuropsychological tests--the Trail-Making Test from the Halstead-Reitan battery and the Digit Symbol Substitution Test--during the testing session conducted while the subjects were partially recovered.

Acute Disease↗