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The effect of zero-balanced ultrafiltration during cardiopulmonary bypass on S100b release and cognitive function.

Zero-balanced ultrafiltration (ZBUF) might reduce the systemic inflammatory response (SIRS) during cardiopulmonary bypass (CPB) by removing inflammatory mediators. The objective of this study was to determine the effect of ZBUF on postoperative serum S100b levels, a marker of neuronal injury. In addition, the possible effects of ZBUF on postoperative neurocognitive function were assessed. Sixty patients undergoing elective coronary bypass grafting were randomly assigned either to a control group or to a protocol group in which ZBUF was performed. Serum S100b levels were measured five minutes after intubation, at the end of bypass and eight and 20 hours after arrival at the intensive care unit (ICU). Cognitive function was assessed with neuropsychological tests on the day before the operation and the sixth day after surgery. The S100b level at 20 hours after arrival at the ICU was 0.27 g/L (SD 0.16) in the control and 0.25 g/L (SD 0.12) in the group with ZBUF. There were no statistical differences at any time between the two groups. S100b was not detectable in the ultrafiltrate, indicating that these results were not obscured by washout of S100b. Thirteen patients (52%) in the control group and 14 patients (56%) in the ZBUF group showed a cognitive deficit. In conclusion, ZBUF during CPB does not decrease the release of S100b. This result is not affected by washout. ZBUF did not reduce the incidence of early neurocognitive deficits. The role of SIRS in the development of cognitive dysfunction following CPB remains to be resolved.

Aged↗

[Musical perception and cognitive functions. Is there such a thing as the Mozart effect?].

INTRODUCTION: Throughout the second half of the 20th century important advances were made in the study of neurobiology related to the processing of music, the differences and similarities between the neural pathways involved in language and in music, the role played by each hemisphere in recognising these stimuli, and the effects that exposure to certain specific pieces of music could have on the cognitive functions. DEVELOPMENT: The objective of this study is to review the literature concerning music and the central nervous system, bearing in mind the above-mentioned aspects. Likewise, we also wanted to analyse the reports referring to the Mozart effect and Tomatis, in addition to those dealing with formal musical education and its effects. The increased capacity to respond in visuospatial-type tasks after exposure to music by Mozart has triggered a commercial boom which makes use of isolated data, while the real extent of the effect remains unknown. CONCLUSIONS: After reviewing the scientific literature on this subject, it was found that the effects of exposure to music by Mozart (the 'Mozart effect') when they actually occurred, were limited to a specific skill that did not last for more than a few minutes. Formal musical education, on the other hand, shows more permanent positive effects but which can be attributed to the individual attention the pupil receives and to the stimulation in basic skills for general learning.

Auditory Perception↗

Prophylactic cranial irradiation dose effects on late cognitive function in children treated for acute lymphoblastic leukemia.

Prophylactic central nervous system treatment has dramatically improved the disease-free survival of children with acute lymphoblastic leukemia (ALL). Long-term neuropsychological sequelae are documented in children who received 2400 cGy prophylactic cranial irradiation. The dose was reduced to 1800 cGy. Available reports on developmental consequences, with short follow-up, have yielded inconsistent results. This study assesses radiation dose effects on cognitive function in children with leukemia who received central nervous system prophylaxis with 2400 cGy versus 1800 cGy whole brain radiotherapy. All leukemic children also received intrathecal methotrexate. A control group of children (treated for Wilms' tumor) received no central nervous system therapy. Nineteen children were treated with 2400 cGy, 16 children with 1800 cGy. The 12 control children received no irradiation. All patients were off therapy for at least 70 months. The 1800 cGy and 2400 cGy patient groups were off therapy for equivalent periods of time (range 70-123 mo) at follow-up testing. Mean age at diagnosis was 49 months, at testing: 142 months. The male to female ratio was 1/1. Standardized psychological tests were administered. Full-Scale, Verbal, and Performance IQ were measured with the Wechsler Intelligence Scale for Children-Revised. Wide Range Achievement Testing evaluated reading, spelling, and arithmetic abilities. Children treated with 1800 cGy performed significantly better than those who received 2400 cGy, and at the same level as controls. There were statistically significant differences between the 1800 cGy and 2400 cGy subjects in all measures. 2400 cGy patients had deficiencies in IQ and academic performance. 1800 cGy patients scored approximately 12 points higher than 2400 cGy children. Eleven children, two in the control group, two in the 1800 cGy, and seven in the 2400 cGy group had IQ scores of less than 90. Eight of the nine irradiated children with deficits had radiotherapy before age 5. These results indicate a mild, but diffuse information processing deficit in children who received 2400 cGy, but not in children who received 1800 cGy. These findings with a minimum of 6 years of follow-up provide new information on late effects of CNS prophylaxis in ALL. Reducing the cranial RT dose from 2400 cGy to 1800 cGy reduced neurotoxicity to acceptable levels.

Brain↗

Prospective randomized trial of normothermic versus hypothermic cardiopulmonary bypass on cognitive function after coronary artery bypass graft surgery.

BACKGROUND: Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery. METHODS: Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5-36.5 degrees C) or hypothermic (28-30 degrees C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale. RESULTS: Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment. CONCLUSIONS: Hypothermic CPB does not provide additional central nervous system protection in adult cardiac surgical patients who were maintained at either 30 or 35 degrees C during CPB.

Anesthetics, Intravenous↗

Relation of cortical language distribution and cognitive function in surgical epilepsy patients.

PURPOSE: To investigate the relation between the number and spatial distribution of language sites and specific patient-and epilepsy-related variables. METHODS: Patients with stimulation-induced reading or naming errors from anterior or inferior temporal cortex (i.e., atypical temporal language sites) were compared with those with language sites confined to Wernicke's area (WA) in the posterosuperior temporal and inferior parietal perisylvian area. In a consecutive series of 44 left hemisphere language dominant patients with complex partial seizures before left temporal lobectomy, correlations were compared between cortical language distribution and measures of cognitive function. RESULTS: Patients with atypical temporal language sites (group 1) had significantly fewer years of education that did patients with language sites in WA (group 2). Patients in group 1 had poorer verbal learning and fluency than did patients in group 2. Patients with IQ <80 were significantly more likely to have multiple sites where stimulation disrupted language than did patients with normal IQ. Number of language sites had significant negative correlations with full-scale IQ, and measures of confrontation naming, verbal fluency, and immediate verbal memory. CONCLUSIONS: Language cortex has a wider spatial distribution in epilepsy surgery patients with lower intelligence, poorer education, and worse verbal and memory skills.

Adult↗

Effects of sibutramine alone and with alcohol on cognitive function in healthy volunteers.

AIMS: To investigate the effects of sibutramine in combination with alcohol in a double-blind, randomised, placebo-controlled, four-way crossover study in 20 healthy volunteers. METHODS: On each study day each volunteer received either: sibutramine 20 mg+0.5 g kg-1 alcohol; sibutramine 20 mg+placebo alcohol; placebo capsules+0.5 g kg-1 alcohol; or placebo capsules+placebo alcohol. Alcohol was administered 2 h following ingestion of the study capsules. During each study day, assessments of cognitive performance were made prior to dosing, and at 3, 4.5, 6 and 10 h post dosing. Blood alcohol concentration was estimated using a breath alcometer immediately prior to each cognitive performance test session. Each study day was followed by a minimum 7 day washout period. RESULTS: Alcohol was found to produce statistically significant impairments in tests of attention (maximum impairment to speed of digit vigilance=49 ms) and episodic memory (maximum impairment to speed of word recognition=74 ms). Alcohol also increased body sway (maximum increase 17.4 units) and lowered self rated alertness (maximum decrease 13.6 mm). These effects were produced by an inferred blood alcohol level of 53.2 mg dl-1. Sibutramine was not found to potentiate any of the effects of alcohol. There was a small, yet statistically significant, interaction effect observed on the sensitivity index of the picture recognition task. In this test, the combined effects of sibutramine and alcohol were smaller than the impairments produced by alcohol alone. Sibutramine, when dosed alone, was associated with improved performance on several tasks. Sibutramine improved attention (mean speed of digit vigilance improved by 21 ms), picture recognition speed (improvement at 3=81) and motor control (tracking error at 3 h reduced by 1.58 mm). Also sibutramine improved postural stability (reducing body sway at 3 h by 14.2 units). Adverse events reported were unremarkable and consistent with the known pharmacology of sibutramine and alcohol. CONCLUSIONS: There was little evidence of a clinically relevant interaction of sibutramine with the impairment of cognitive function produced by alcohol in healthy volunteers. The single statistically significant interaction indicated a reduction, rather than a worsening, of alcohol-induced impairment when sibutramine is taken concomitantly. Sibutramine when administered alone is associated with improved performance on several tasks.

Adult↗

An improvement in cognitive function following polypharmacy reduction in a group of epileptic patients.

18 epileptic patients on polypharmacy were assessed, using a battery of psychometric tests including the Wechsler Adult Intelligence Scale, Benton Visual Retention Test and Alertness and Concentration tests. The same patients were reassessed one year later following a trial to reduce their polypharmacy. The results for 12 patients whose treatment was reduced to monotherapy were statistically analysed, using the Wilcoxon Matched Pairs Test. Significant changes were found on a number of test scores which included Full Scale WAIS I.Q., W.A.I.S. Performance I.Q., Digit Symbol, Block Design and Object Assembly, Benton Visual Retention Test Error Score and Concentration Test Score. The other tests showed no improvement over baseline. The results point to the improvement in some areas of cognitive function which follows a reduction in polypharmacy to monotherapy.

Adult↗

beta-APP cognitive function versus beta-amyloid--induced cell death.

The beta-amyloid precursor protein (beta-APP) has been hypothesized to play an important role in the establishment of synaptic connections. Icv injections of anti-beta APP antibodies into rat brains produced no appreciable effect on subsequent learning of a passive avoidance task whereas memory assessed 1 day later in a retention test was impaired in anti-beta-APP--but not control-IgG-injected animals. This suggests a possible involvement of beta-APPs in cognitive functions. In order to evaluate the properties of the proteolytic A beta-fragment accumulating in Alzheimer's disease brains, four different neuronal cell types were exposed to A beta 1-42 for 24 hours. All cells degenerated in response to A beta, yet chromosomal condensation and internucleosomal DNA fragmentation, typical for apoptosis, occurred in only three of the cell types tested. These findings suggest that beta-APPs may play an important role in cognitive processes and additionally, that their alternative proteolytic product A beta may be differentially toxic to neuronal cell types, inducing cell death either by necrosis or by apoptosis.

Amyloid beta-Peptides↗

Thyroid status, disability and cognitive function, and survival in old age.

CONTEXT: Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders. OBJECTIVES: To determine whether subclinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age. DESIGN, SETTING, AND PARTICIPANTS: A prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in the municipality of Leiden, the Netherlands. A total of 599 participants were followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7 [1.4] years). MAIN OUTCOME MEASURES: Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years. RESULTS: Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status. The hazard ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95% CI, 1.04-1.30; P = .009). CONCLUSIONS: In the general population of the oldest old, elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span. However, evidence for not treating elderly individuals can only come from a well-designed, randomized placebo-controlled clinical trial.

Activities of Daily Living↗

Carotid surgery, cognitive function, and cerebral blood flow in patients with transient ischemic attacks.

Psychological testing, cerebral blood flow (CBF) measurement, and computed tomographic scan were performed before and 3 months after operation in 31 patients subjected to endarterectomy of the internal carotid artery (ICA) because of transient ischemic attacks and in 11 control patients operated on for atherosclerosis of the lower extremities. In preoperative psychological testing both carotid surgery patients and controls performed somewhat below the normal level for their age group. Postoperatively, cognitive functions improved in the carotid surgery group but not in the control group. The improvement was related to the laterality of the operation, being more marked in verbal tests in patients with left ICA operation and in visuospatial tests in patients with right ICA operation. Postoperatively regional CBF improved in 2 patients only. Hence the intellectual improvement could not be related to changes in CBF. Intellectual deterioration in patients with internal carotid atherosclerosis may be delayed or terminated by surgical abolition of the source of multiple cerebral embolizations.

Adult↗

Effects of acute tryptophan depletion on mood and cognitive functioning in older recovered depressed subjects.

OBJECTIVE: Previous studies show that acute tryptophan depletion (ATD), by administration of an amino acid drink lacking tryptophan, can produce clinically significant depressive symptoms in subjects who have recovered from major depression. This is more likely in female patients who have had suicidal ideation, recurrent depression, and treatment with specific serotonin reuptake inhibitors. These risk factors are frequent in older recovered depressed people. The authors investigated the effects of ATD on mood and cognitive functioning in this group. METHODS: Sixteen recovered depressed (RD) subjects and 17 healthy-comparison subjects, over 60 years old, participated in a double-blind, placebo-controlled, crossover study involving administration of a tryptophan-depleting and a placebo drink. Mood ratings scales were administered at baseline and at 4 and 7 hours post-drink on each test day. A battery of neuropsychological tests, including the modified Mini-Mental State Examination (MMSE) was administered between 4 and 6 hours post-drink. RESULTS: Depletion of plasma free tryptophan was 71% at 4 and 7 hours after the active drink. There was no evidence of mood change at any time in either group. On the MMSE, however, the ATD/RD group showed a significant decrease compared with placebo. CONCLUSIONS: There was no evidence of mood disturbance during ATD in any subject. This may imply less sensitivity to acute disturbance of the 5HT system than in younger recovered patients.

Adult↗

Rethinking cognitive function in multiple sclerosis: a nursing perspective.

Cognitive impairment is a common problem in multiple sclerosis (MS); up to 65% of patients exhibit some neuropsychological dysfunction during the course of their disease. It is a major contributing factor to unemployment, accidents, impairment of daily functioning, and loss of social activity in those affected by MS. The areas of cognition typically impaired are memory, attention, information processing, executive functions, and visuospatial skills. Cognitive dysfunction is independent of disease duration and level of disability; cognitive decline may begin in the earliest stages of MS before patients become even mildly disabled. Structural brain imaging studies show a positive correlation between the extent of brain atrophy and cognitive dysfunction. Despite its prevalence in MS, cognitive dysfunction often goes undiagnosed or is misdiagnosed as depression, stress, stubbornness, lack of intelligence, or psychosis. Because nurses play such an important role in the care of patients with MS, they are in a position to identify patients with cognitive dysfunction, educate patients and their families on ways to cope with cognitive deficits, and counsel patients on available treatment options. Practical guidelines help nurses identify and care for cognitively impaired MS patients.

Cognition Disorders↗

[Assessment of cognitive function after preventive and therapeutic whole brain irradiation using neuropsychological testing].

PURPOSE: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. PATIENTS AND METHOD: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). RESULTS: Patients with SCLC showed test results significantly below average before PCI (n = 28, mean IQ = 83, SD = 17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). CONCLUSION: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible.

Adult↗

Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy.

Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs were given additional vigabatrin (1 g twice daily for six weeks, followed by 1.5 g twice daily for a further six weeks) and matched placebo in a double blind, randomised, crossover study. A battery of neuropsychological tests was administered at baseline and at weeks two, six and 12 of both treatment periods. No significant differences were found between vigabatrin and placebo at any time point for any of the objective tests of cognitive function. Patients, however, reported a greater degree of sedation after two and six weeks on vigabatrin than during the equivalent placebo phase (p < 0.01), although no such difference was apparent at 12 weeks. Follow up over a mean of 14.75 months in 12 responders, who continued on vigabatrin, revealed a significant improvement (all p < 0.01) on each of three composite scales (three psychomotor tests, four memory tests, three self rating scales) compared with their scores during the double blind trial. Vigabatrin did not cause cognitive impairment either acutely or in the long term. Phased introduction, however, seems a prudent policy to allow tolerance to early subjective sedation.

Adolescent↗

Effects of chronic hypertension on cognitive functioning.

Arterial hypertension and blood pressure level are associated with modestly accelerated cognitive decline over the adult life span and with moderately increased risk of poor cognitive performance at all ages. Correlations between white matter lesions in brain and elevated blood pressure provide indirect evidence that structural and functional changes in brain over time may lead to lowered of cognitive functioning when blood pressure control is poor or lacking. Preventive methods designed to lower population blood pressure, early detection, and aggressive treatment of hypertension are important to prevent accelerated cognitive decline in the individual and to preserve cognitive ability in the population. Some evidence suggests that poorly controlled hypertension may predispose to the dementias, but more work is needed to ascertain this.

Chronic Disease↗

Effects of a new slow release formulation of caffeine on EEG, psychomotor and cognitive functions in sleep-deprived subjects.

Caffeine is a widely-consumed psychoactive substance whose stimulant effects on mood, attention and performance are largely recognised. The central nervous system pharmacodynamic profile of a single oral dose of a new slow release (SR) caffeine formulation (600 mg) was assessed in a randomised, double-blind, crossover, placebo-controlled study. Twelve young, health, male, sleep-deprived (for 36 h) subjects were studied using EEG and various measures of psychomotor and cognitive functions, including critical flicker fusion (CFF), choice reaction task (CRT), tracking, continuous performance task (CPT), Stroop test, body sway and subjective evaluation (Stanford Sleepiness Scale). Caffeine significantly ( < 0/05) antagonised the detrimental effects of sleep-deprivation on EEG (i.e. produced a significant decrease in delta and theta relative power and a significant increase in alpha and beta (12-40 Hz) relative power) and psychomotor performance (significant increase in speed of reaction on the CRT and Stroop tests, significant decrease in body sway, significant increase in accuracy of the CPT and significant reduction in subjective sedation) compared to placebo. The effect peaked 4 h after dosing and was maintained until the end of sleep deprivation (i.e. 24 h after dosing). In conclusion, the present results demonstrate that a single dose of caffeine SR possesses alerting effects which are able to reverse the deleterious effect of 36 h sleep deprivation for at least 24 h. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

Effect of topiramate on cognitive function and activity level following neonatal seizures.

Topiramate, an antiepileptic drug with a number of mechanisms of action including blockade of AMPA/KA receptor subtypes, was assessed as a neuroprotective agent following seizures. We administered topiramate or saline chronically during and following a series of 25 neonatal seizures. After completion of the topiramate treatment, animals were tested in the water maze for spatial learning and the open field for activity level. Brains were then examined for cell loss and sprouting of mossy fibers. Rats treated with topiramate performed significantly better in the water maze than rats treated with saline. Topiramate treatment also reduced the amount of seizure-induced sprouting in the supragranular region. There were no differences between topiramate- and saline-treated rats in activity level in the open field, swimming speed, or weight gain. These findings show that long-term treatment with topiramate after neonatal seizures changes the long-term consequences of seizures and improves cognitive function.

Age Factors↗

Variables associated with cognitive function in elderly California Seventh-day Adventists.

From a cohort of white, non-Hispanic California Seventh-day Adventists, 99 subjects over age 75 years in 1991 were randomly selected. Dietary habits and educational status had been measured in 1976. Subjects completed the Mini-Mental State Examination (MMSE) in 1991, and at that time, they or caregivers also gave information on current medical problems and drug therapy. Those who ate more calories in 1976 had lower MMSE scores in 1991 (p = 0.03), an association strengthened by excluding those with previous stroke or Parkinson's disease by 1991. This raises the possibility that higher consumption of calories in middle age may accelerate the decline in cognitive function seen with aging, as apparently occurs in some animals. Less-educated subjects had lower MMSE scores, especially among the very elderly. The statistical model predicts that the negative association between use of psychotropic drugs and MMSE score (p = 0.004) is particularly potent in those cognitively impaired for other reasons. If causal, this suggests that physicians should use these agents very cautiously in such subjects.

Aged↗