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PubMed1997

Cognitive effects of antipsychotic agents in persons with traumatic brain injury.

Over 1 million survivors of traumatic brain injury receive maintenance pharmacotherapy, of which a substantial number receive antipsychotic agents for the treatment of psychoses, agitation and aggression, and other maladaptive behaviours. In spite of the common clinical uses of antipsychotics, the cognitive risks versus benefits are unclear. The purpose of this study was to assess differences in cognitive functioning before, during, and after discontinuation of antipsychotic agents in inpatients undergoing rehabilitation for traumatic brain injury. Neuropsychiatric tests (Reys Auditory-Verbal Learning, Trail Making A&B, Digit Span Forwards and Backward) evaluating cognitive skills of verbal ability, visuomotor speed, memory, learning, attention, and spatial ability were administered to each subject at baseline (immediately prior to tapering or discontinuing antipsychotic), when taper reached 50% of baseline dose, 1 week after antipsychotic discontinuation, and 3 weeks after discontinuation. These data suggest that select areas of cognition improve after antipsychotic discontinuation in subjects with traumatic brain injury. The magnitude of improvement appeared to be greater after discontinuation with thioridazine, a low-potency agent, compared to haloperidol, a high-potency agent. Results, although very preliminary, support the hypothesis of cholinergic involvement in regulating cognitive processes, and this underscores the need for more systematic research in this area.

Adult↗
PubMed1994

Mild sustained effects of neonatal vasopressin and oxytocin treatment on brain growth and behavior of the rat.

The lasting effects of a 9-day neonatal exposure to vasopressin and oxytocin were examined in the rat to discover if peptide administration results in organizational effects. When tested in young adulthood, brain growth, not body growth, appeared to be impaired. Basal and challenge tests of urine production, carried out to see the development of the hormonal antidiuretic function of vasopressin, revealed no lasting changes, and therefore did not confirm earlier findings of an induced mild polyurea. Behavioral testing of learning by making use of a one-trail step-through paradigm with a 24-h retention trial--a test that is sensitive to vasopressin--did not show impairments. Open field tests, however, showed enhanced emotionality in the vasopressin-treated females, as well as an initially increased ambulation in the males, and increased grooming in both sexes, the latter also having been reported to be induced by vasopressin administration in the septal areas. Oxytocin treatment did not produce lasting changes. Our conclusion, therefore, is that peripherally circulating vasopressin can affect the organizational development of the rat brain. It remains to be established whether this is an effect obtained through changes in the general peripheral physiology or a reflection of plasticity phenomena at the level of central vasopressin neurotransmission.

Animals↗
PubMed1979

The effect of regular exercise on cognitive functioning and personality.

The effect of regular exercise on cognitive functioning and personality was investigated in 32 subjects representing 4 discrete groups based on sex and age. Before and after a 10 week exercise programme of jogging, calisthenics, and recreational activities, a test battery was administered to assess functioning in a number of domains: intelligence (WAIS Digit Symbol and Block Design); brain function (Trail-Making); speed of performance (Crossing-Off); memory and learning (WMS Visual Reproduction and Associate Learning); morale and life satisfaction (Life Satisfaction and Control Ratings); anxiety (MAACL); and depression (MAACL). Improvement was observed on several physiological parameters. ANOVA revealed significant sex and age differences on Digit Symbol and Block Design and age differences on Trail-Making, Crossing-Off, Associate Learning, and anxiety. Regardless of sex and age, significant improvement in performance was observed from pre to post-test on Digit Symbol, Block Design, Trail-Making, Crossing-Off, and on Associate Learning. In addition, an increase on health status rating (p less than .01) and decrease in anxiety were observed from pre to post-test. These data illustrate beneficial effects of exercise on certain measures of cognitive functioning and personality.

Adult↗
PubMed1997

Cumulative blood lead levels and neurobehavioral test performance.

The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioral tests in adults. One of reasons for this controversy is the lack of studies with good cumulative exposure to or dose of lead. The aims of this study are to compare the neurobehavioral test performances of a group of lead-exposed workers and a referent group, and to study the association of the neurobehavioral test performances with concurrent blood lead levels and cumulative blood lead levels. Fifty lead battery workers and 97 non-exposed (referent) workers from a vehicle maintenance workshop were evaluated on their neurobehavioral performance using the World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB). The geometric mean concurrent blood lead (ConPb) of the exposed and referent groups were 37.1 (range 13.2-64.6) microg/100 ml and 6.1 (range 2.4-12.4) microg/100 ml, respectively. Cumulative blood lead (CumPb) was defined as area under the curve for the number of years each worker was exposed to lead (three workers previous blood lead results were not available). ConPb and CumPb were used to study the association with the neurobehavioral test results. The exposed group had significantly poorer manual dexterity, perceptual-motor speed, and motor steadiness compared with the referents. The standardized partial regression coefficients were higher for CumPb than ConPb for most of the neurobehavioral test results. In the group >35 years old, there were significantly stronger associations between CumPb and Digit Symbol and Trail Making Part A results than for ConPb which are tests of perceptual and motor skills. CumPb was a better predictor than ConPb of the effects of lead on neurobehavioral performances.

Adult↗
PubMed1988

The effects of acute sleep deprivation during residency training.

Verbal and symbol concentration, learning, problem solving, clear thinking, manual skills, and memory were tested in 42 surgical residents to assess the effects of acute sleep deprivation on specific neuropsychological parameters. A series of eight neuropsychological tests--digit symbols, digit vigilance, story memory, trail making, PASAT, Raven matrices, delayed story, and pegboard--and a questionnaire on mood states were completed by the residents both when fatigued (less than 4 hours of sleep: mean, 2.0 +/- 1.5 hours) and when rested (more than 4 hours of sleep: mean, 6.5 +/- 1.0 hours), with at least 7 days between tests. In order to eliminate the effects of learning from the first test series, randomization of residents was performed so that one half were first evaluated when rested and one half when fatigued. ANOVA, multiple regression analysis, and the Student t test were used to assess differences. In the acute sleep-deprived state, residents were less vigorous and more fatigued, depressed, tense, confused, and angry (p less than 0.05) than they were in rested state. Despite these changes in mood, however, the responses on all of the functional tests were no different statistically in those who were rested and those who were fatigued (even in those with less than 2 hours' sleep). We conclude that acute sleep deprivation of less than 4 hours alters mood state but does not change performance in test situations in which concentration, clear thinking, and problem solving are important.

Adult↗
PubMed1994

Effects of sleep deprivation on naval seamen: II. Short recovery sleep on performance.

Twenty male naval volunteers, aged 18 to 20 years, with 12 to 14 years of education, underwent a total sleep deprivation experiment on board a Republic of Singapore Navy landing ship in the South China Sea for a period of 42-102 hours. The sleep group comprised eight volunteers who dropped out at the 44th-46th h of the experiment and were randomly assigned to a 2 or 4 h sleep regime. The rest served as sleep-deprived controls. Neurobehavioural performance tests, profile of mood state and the Stanford Sleepiness Scale were applied 6 hourly starting from 6.00 am on the first experimental day. No thresholds were observed in the performance of tests related to manual tasks and subjective feeling, including naval tasks, mood and sleepiness scale during the sleep deprivation experiment. However, thresholds were observed in the performance of tests requiring cognitive and perceptive skills, including the grooved peg board, trail making, sea-shore rhythm, addition, digit span, digit symbol, flicker fusion and dynamometer tests. Performances in these tests were observed to deteriorate only after approximately 30 h of sleep deprivation. The Z score for the non-threshold tests (Z-N) deteriorated from -0.01 at the start of the experiment to 1.25 at the 42nd h of the experiment just before the imposed sleep and improved to 0.81 at the 48th h of the experiment just after the imposed sleep; and the Z score for the threshold tests (Z-T) varied from -0.07 at the start to 0.49 just before sleep (at the 42nd h) and to continuously deteriorate to 0.83 just after sleep (at the 48th h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Multiple sclerosis: correlation of anxiety, physical impairment and cognitive dysfunction.

The aim of the study was to examine the correlation between anxiety and physical impairment and to discover whether anxiety correlated with specific forms of cognitive dysfunction. Ninety-four patients (42 females, 52 males) with definite MS entered the study. Anxiety was measured using the State-Trait Anxiety Inventory, physical impairment by means of the Kurtzke Disability Status scale, and cognitive impairment by using the Trail Making, Symbol Digit Modalities, Auditory Verbal Learning, Story Recall and the Recurring Figures tests. Moderately handicapped patients (DSS 4-5) showed signs of anxiety, and physical impairment correlated with anxiety (p < 0.05; d.f. 1.92). Trail Making also correlated with anxiety (p < 0.01; d.f. 1.86). On the basis of the results of this and previous studies, it is concluded that anxiety can be a sign of cognitive dysfunction, physical impairment or social strain.

Adult↗
PubMed1995

Smooth pursuit eye movements and neuropsychological impairments in schizophrenia.

Smooth pursuit eye movements (SPEM) and neuropsychological performance were examined in a sample of 29 drug-treated schizophrenic patients and 22 healthy controls. Patients had impairment in SPEM as well as in a wide range of neuropsychological tests (Wechsler Adult Intelligence Scale, Wisconsin Card Sorting Test. Finger Tapping, Reaction time, Selective attention, Trail-Making and Simultaneous Capacity). Performance indices were more affected than strategy-executive indices. Drug type (clozapine vs typical) and dose (chlorpromazine units) were not related to neuropsychological impairment among the patients. Indices from the whole range of tests accurately predicted a subjects' group identity (patient vs control). Impaired SPEM was predicted more accurately by tests assessing frontal functions. Seven patients, all men, had only marginal neuropsychological impairments.

Adult↗
PubMed2002

Rate of fall of blood glucose and physiological responses of counterregulatory hormones, clinical symptoms and cognitive function to hypoglycaemia in Type I diabetes mellitus in the postprandial state.

AIMS/HYPOTHESIS: The aim of this study was to establish the effect of a rate of decreasing plasma glucose concentrations on responses to hypoglycaemia, i.e. release of counterregulatory hormones, perception of symptoms, deterioration of cognitive function, and rates of forearm noradrenaline spillover, in the postprandial condition and in the sitting position. METHODS: We studied 11 subjects with Type I (insulin-dependent) diabetes mellitus, twice during clamped insulin-induced hypoglycaemia (2.4 mmol/l) after eating in the sitting position. On one occasion, plasma glucose was decreased at the rate of 0.1+/-0.003 mmol x min(-1) x l(-1) (fast fall), on the other at the rate of 0.03+/-0.001 mmol x min(-1) x l(-1) (slow fall). Subjects underwent a control euglycaemic clamp study as well. RESULTS: In response to fast-fall as compared to slow-fall hypoglycaemia, which was about 30 min longer, cognitive tasks were performed as follows: Trail-Making B, PASAT 2 s, Digit Vigilance Test and Verbal Memory deteriorated more, adrenaline increased less (2.8+/-0.5 vs 3.5+/-0.7 nmol/l, p=0.03), forearm noradrenaline spillover was greater (6.5+/-1.0 vs 5.2+/-0.4 pmol x min(-1) x 100 ml(-1), p=0.04), and symptoms were no different. After recovery from hypoglycaemia, cognitive function was still deteriorated compared to the baseline with no difference between fast and slow-fall hypoglycaemia. The evident response of glucagon to postprandial hypoglycaemia contrasted with the blunted or absent response in the fasting state. CONCLUSION/INTERPRETATION: In the postprandial condition and sitting position, fast-fall hypoglycaemia is more dangerous than slow-fall, because it deteriorates cognitive function more, and activates responses of counterregulatory hormones less than slow-fall hypoglycaemia.

Adult↗
PubMed2005

Neuropsychological measures of attention and memory function in schizophrenia: relationships with symptom dimensions and serum monoamine activity.

BACKGROUND: Some clinical symptoms or cognitive functions have been related to the overall state of monoamine activity in patients with schizophrenia, (e.g. inverse correlation of the dopamine metabolite HVA with delusions or visual-masking performance). However, profiles (as presented here) of the relations of the activity of dopamine, noradrenaline and serotonin to neuropsychologic (dys)functions in major patient sub-groups with their very different symptomatic and cognitive characteristics have not been reported. METHODS: Serum measures of dopamine, noradrenaline and serotonin turnover were examined by regression analyses for the prediction of performance on 10 neuropsychological measures reflecting left- and right-hemispheric and frontal-, parietal- and temporal-lobe function in 108 patients with schizophrenia and 63 matched controls. The neuropsychological battery included tests of verbal fluency, Stroop interference, trail-making, block-design, Mooney faces recognition, picture-completion, immediate and delayed visual and verbal recall. Paranoid and nonparanoid subgroups were based on ratings from the Positive and Negative Syndrome Scale (PANSS). Groups with high and low ratings of ideas-of-reference and thought-disorder were formed from a median split on the Scale for Assessment of Positive Symptoms (SAPS). RESULTS: Verbal-fluency and Stroop-interference (left frontal and fronto-cingulate function) were negatively associated with noradrenergic turnover in nonparanoid and thought-disordered patients. High dopamine turnover related to speeded trail-making (frontal modulation of set switching) in those with many ideas-of-reference. In contrast, low dopamine turnover predicted poor recall in nonparanoid patients and those with little thought disorder. Serotonin metabolism did not independently contribute to the prediction any measure of cognitive performance. But, with regard to the relative activity between monoaminergic systems, increased HVA/5-HIAA ratios predicted visual-reproduction and Mooney's face-recognition performance (right-hemisphere functions) in highly symptomatic patients. Decreased HVA/MHPG predicted non-verbal recall. CONCLUSION: Clinical state and function are differentially sensitive to overall levels of monoamine activity. In particular, right-lateralised cerebral function was sensitive to the relative activities of the monoamines. Increased noradrenergic activity was associated with enhanced frontal but impaired temporal lobe function in nonparanoid syndromes. Low dopaminergic activity predicted poor attentional set control in those with ideas-of-reference, but poor recall in nonparanoid patients. These data, especially the HVA/5-HIAA ratios, provide a basis for planning the nature of antipsychotic treatment aimed at patient specific symptom dimensions and cognitive abilities.

Journal Article↗
PubMed1999

Attention: neuropsychological predictor of competency in Alzheimer's disease.

This study was undertaken to examine the relationship between two different competencies, financial and medical decision making, and explore whether neuropsychological testing can identify a common underlying cognitive operation impaired in patients with AD. The objective was to examine the neuropsychological predictors of financial and medical decision-making competencies in patients with Alzheimer's disease (AD). Twenty individuals with mild to moderate AD and 20 control subjects matched for age and education were evaluated at a university medical center. All participants were administered a financial competency questionnaire, a competency test for medical decision making, and a set of standardized neuropsychological tests selected to reflect cognitive processes theoretically related to competency. In addition, an informant provided information regarding banking history for each participant. AD patients performed more poorly on all measures, including both measures of competency, which were highly related (R = .718, P < .001). Two tests, Trails A and Word List Recall, were significantly correlated with both competency measures, with Trails A predicting over 85% of the variance in competency scores. Trails A discriminated competent from not competent participants with an accuracy ranging from 77% to 82%. Measures of financial and medical decision-making competency were significantly correlated among patients with AD. One brief neuropsychological test of attention, Trails A, proved to be highly predictive of performance on both competency measures and useful in the discrimination of competent performance on these measures and by informant report.

Aged↗
PubMed1998

Executive-frontal lobe cognitive dysfunction in schizophrenia: a symptom subtype analysis.

Impairment of executive-frontal lobe functioning, affecting the planning, initiation and regulation of goal-directed behavior, is a common cognitive deficit in schizophrenia. However, it is unclear if deficits in these frontal-lobe-mediated abilities are differentially expressed across clinical subgroups. We analyzed executive-frontal abilities in relation to symptom expression in 53 hospitalized schizophrenic patients. Patients were assigned to one of three subgroups based on rank order analysis of Brief Psychiatric Rating Scale factors: Withdrawal-Retardation, Reality Distortion and Conceptual Disorganization. Executive-frontal tests included Visual Search, Verbal Fluency, Verbal Series Attention, Trail Making - Part B, Symbol Digit, Hopkins Verbal Learning, Digit Span, Wisconsin Card Sorting, Stroop Color-Word and Attentional Capacity. The schizophrenia group showed significant deficits relative to healthy control subjects (n = 20) on all tests. Exploratory factor analysis of test scores revealed three factors: (i) Verbal Processing/Memory; (ii) Cognitive Flexibility/Attention; and (iii) Psychomotor Speed/Visual Scanning. The three symptom subgroups were differentially impaired on executive-frontal abilities: Withdrawal-Retardation on psychomotor speed, verbal fluency, working memory, visual search and cognitive flexibility; Conceptual Disorganization on attention; Reality Distortion on verbal memory. The results have implications for syndrome definition, pharmacological intervention and prediction of outcome in schizophrenia.

Adult↗
PubMed1997

Auditory information processing during acute insulin-induced hypoglycaemia in non-diabetic human subjects.

Acute insulin-induced hypoglycaemia impairs performance on tests of general mental ability in humans. It is recognized that different brain functions vary in their sensitivity to neuroglycopenia, but little is known about the effects of neuroglycopenia on specific brain processes. The effect of controlled hypoglycaemia on two aspects of auditory information processing (auditory temporal processing and simple auditory processing) was examined in a homogeneous group of 20 healthy non-diabetic human subjects. Auditory temporal processing (temporal order discrimination) and simple auditory processing (pitch discrimination, single-tone duration and single-tone loudness discrimination) tests were part of the Test of Basic Auditory Capabilities (TBAC). Two tests of general cognitive performance (Digit Symbol Substitution and Trail Making B) were included to provide a measure of general brain functioning during hypoglycaemia. Hypoglycaemia lead to a significant deterioration in auditory temporal processing (P < 0.01), and a deterioration in one of three tasks of simple auditory processing (discrimination of single-tone loudness, P < 0.05). Significant disruptions also occurred in both tests of general brain functioning. These results are congruent with other studies in human subjects, showing a disruptive effect of hypoglycaemia on visual information processing when examined under conditions of limited perceptual time, and they provide further evidence of the importance of sensory processing speed in basic perceptual and cognitive functions. The disruptive effect of moderate insulin-induced hypoglycaemia on auditory perception may have implications for insulin-treated diabetic humans exposed to this metabolic stress, because of the importance of hearing in everyday life.

Acoustic Stimulation↗
PubMed2000

Visual and neurobehavioral impairment associated with polychlorinated biphenyls.

To determine whether residents exposed to PCBs and thermolysis products had impaired neurobehavioral functions, the performance of 98 exposed adults was compared with 58 unexposed regional referents (all volunteers). Visual field performance, color confusion index, balance as sway speed, blink reflex latency R-1, hearing, grip strength, simple and choice visual reaction times problem solving for Culture Fair and digit symbol, recall memory, peg placement, trail making A and B for attention and dexterity and long-term memory were tested. A profile of mood states (POMS) and questionnaires for chemical exposures, medical histories and the frequency of 35 symptoms were completed. Only statistically significant differences are described. Exposed subjects had slower simple and choice reaction times and faster sway speeds with eyes closed and open. Color discrimination and visual performance scores were lower and visual fields were often constricted. Scores on Culture Fair, digit symbol, vocabulary and verbal recall were lower. Placement of pegs in a slotted pegboard was slower and trail making A and B took longer. Even embedded memory test scores including vocabulary were lower. POMS scores were elevated. There were no competing chemical exposures, confounding factors or other explanations for the findings. Long residential exposure to PCBs was associated with visual defects and impaired neurophysiologic and neuropsychologic functions.

Adult↗
PubMed2004

Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson's disease.

Bilateral subthalamic deep brain stimulation (STN-DBS) and continuous subcutaneous infusion of apomorphine (APM-csi) can provide a comparable improvement on motor function in patients with advanced Parkinson's disease (PD), but the mechanisms by which both therapies exert their effects are different. We analyzed the cognitive effects of APM-csi. We also compared neuropsychological effects induced by STN-DBS and APM-csi in advanced PD to ascertain the neuropsychological aspects relevant in determining the therapeutic procedure that is the most appropriate in a particular patient. We studied 9 patients treated with STN-DBS and 7 patients with APM-csi. Neuropsychological measures included Rey's Auditory-Verbal Learning, Stroop, Trail Making, phonetic verbal fluency, and Judgment of Line Orientation tests. In the APM-csi group, significant changes were not observed in the neuropsychological tests performance. By contrast, in the STN-DBS group, moderate worsening was found in phonetic verbal fluency and Stroop Naming scores that was partially reversible at long-term follow-up and did not have consequences on regular activities. Consequently, these findings could be interpreted as being not relevant in deciding the most suitable treatment in a given patient.

Aged↗
PubMed1989

Lithium antagonism of ethanol-induced intoxication: relationship to intracellular lithium levels.

Seventeen detoxified chronic alcoholics participated in a double-blind trial comparing placebo and lithium (Li+) effects on acute ethanol (1 g/kg) intoxication. In a repeated measures, split-half crossover design, subjects were maintained for 7 days on Li+ or placebo before the ethanol challenge. Plasma Li+ levels on day 7 averaged 1.3 +/- 0.3 mM. Li+ was not more effective than placebo in attenuating ethanol effects across the subjective dimensions of intoxication, desire to drink, and control of drinking and across the cognitive dimensions measured by Trail Making A, Speed of Closure, and the Minnesota Clerical Test. Li+ was not significantly more effective than placebo in preventing the ethanol-induced rise in plasma prolactin. Subjects were divided according to high and low red blood cell (RBC) Li+ intracellular/extracellular Li+ ratios. In a comparison of the Li+ to placebo arms of the trial, the high ratio subjects (n = 9) showed a significant 44% decrease in ethanol-induced intoxication, while the low ratio subjects (n = 8) showed a 15% increase. Furthermore, the high ratio subjects performed better than the low ratio subjects, independent of the ethanol effect, on all tests of cognitive performance. These preliminary data suggest that the Li+ ratio may be a useful tool in defining unique subgroups of alcoholic patients.

Adult↗
PubMed2005

[Diagnosis of Alzheimer's disease in Brazil: cognitive and functional evaluation. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology].

The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimer's disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended.

Academic Medical Centers↗
PubMed1993

The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes.

BACKGROUND: A number of studies have found that cognitive function is impaired in elderly patients with non-insulin dependent diabetes mellitus (NIDDM) when compared with age-matched non-diabetic controls. In addition, it has been reported that elderly NIDDM patients who have poor glycemic control have a greater impairment in cognition that elderly NIDDM patients with good control. We conducted the following prospective study to determine if improved glycemic control would result in an improvement in cognitive function in elderly patients with NIDDM: METHODS: Sixteen untreated elderly patients with NIDDM underwent a battery of neuropsychologic tests on two occasions, separated by at least two weeks. They were then started on an oral hypoglycemic agent. After they had been on a stable dose of medication for 6 months the neuropsychologic tests were repeated. RESULTS: Fasting glucose decreased significantly after treatment (before: 13.8 +/- 1.2 mmol/l; after 8.4 +/- 0.4 mmol/l, p < .01). After 6 months of treatment patients had improvement in their scores on the Grooved Pegboard, Trail Making-Part A, Stroop-Word Naming, Cued Recall and Picture Arrangement tests (all p < .05). CONCLUSIONS: Improved glycemic control in the elderly patient with NIDDM may have beneficial effects on selective areas of cognition.

Affect↗