Does atypical antipsychotic medication improve executive function in schizophrenia?
Explore the source record for details and available documents.
Antipsychotic Agents↗
Biomedical subjects
Alex Collie
Publications and source records attributed to Alex Collie.
Cognitive testing in early phase clinical trials: outcome according to adverse event profile in a Phase I study.
BACKGROUND: It has been proposed that objective cognitive testing provides additional information to that collected via adverse event (AE) recordings. However, in clinical trials of compounds with potentially negative effects on cognition, the results of cognitive testing may overlap with AE recordings. AIMS: To examine cognitive function in subjects who do and do not report sedation-related AEs in a Phase I clinical trial. METHODS: Five computerized cognitive tasks were administered to 28 healthy male volunteers enrolled in a simulated Phase I study using midazolam to induce sedation-related AEs and cognitive dysfunction. For each subject, the magnitude of cognitive change between pre-dose and 1 hr post-dose assessments was calculated. Group and individual level cognitive outcome was compared between subjects who did and did not report sedation-related AEs following administration of 1.75 and 5.25 mg midazolam. RESULTS: At both doses of midazolam, cognitive dysfunction was observed in both subject groups (i.e., those who did and did not report AEs). Analysis of individual outcomes identified consistent cognitive dysfunction among subjects who reported sedation-related AEs. Further, in the 5.25 mg condition a subset of individuals (66.7%) who did not report sedation-related AEs nevertheless displayed substantial cognitive dysfunction. CONCLUSIONS: Following administration of oral midazolam, there is a dissociation between sedation-related AE recordings and performance on computerized cognitive tests of motor function, attention, strategy use and problem solving, learning and delayed recall. Inclusion of computerized cognitive tests in early phase trials may allow identification of subtle cognitive change, beyond that which is possible by self-report and clinical observation.
Adolescent↗
Fatigue-related impairment in the speed, accuracy and variability of psychomotor performance: comparison with blood alcohol levels.
Cognitive performance is impaired by fatigue arising from sustained wakefulness and alcohol. Three recent papers directly compared the effects of increasing fatigue and blood alcohol concentration (%BAC) to provide a framework for understanding fatigue-related cognitive impairment. While the expression of fatigue-related cognitive impairments in terms of %BAC equivalents is sound, the methodology in each study was flawed in that the statistics used to compare the effects of %BAC and fatigue on cognition did not account for variation between or within each condition. The point estimates of the difference between a baseline and any level of fatigue or %BAC provided no indication of the size of difference that could reasonably be expected by chance. Importantly, all studies showed that variation increased as cognitive performance declined because of both increasing fatigue and %BAC. The current study compared the effect of increasing levels of %BAC and fatigue on the simple reaction task from the CogState test battery on 40 healthy adults using statistical methods that account for intra-individual and within-group variability in performance. After 24 h of sustained wakefulness and with 0.08%BAC, individuals showed maximal cognitive impairment; however, the magnitude of impairment found for fatigue was equivalent only to that observed for 0.05%BAC. Re-analysis of the data using percentage change scores indicated that the magnitude of fatigue-related cognitive impairment was much greater than that detected for 0.08%BAC. This suggests that previous studies that have not accounted for variability in the performance data have overestimated the effect of fatigue on cognitive performance.
Adolescent↗
Saccade and cognitive impairment associated with kava intoxication.
Kava is an extract from the Piper methysticum Forst. f. plant that has social and spiritual importance in Pacific islands societies. Herbal remedies that contain kava are used for the psychiatric treatment of anxiety and insomnia. Laboratory studies have found only subtle, if any, changes on cognitive or motor functions from the acute effects of consuming small clinical doses of kava products. Intoxication from recreational doses of kava has not been studied. The performance of individuals intoxicated from drinking kava (n=11) was compared with a control group (n=17) using saccade and cognitive tests. On average, intoxicated individuals had consumed 205 g of kava powder each (approximately 150 times clinical doses) in a group session that went for 14.4 h and ended 8 h prior to testing. Intoxicated kava drinkers showed ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task that only became evident as the task complexity increased. Kava intoxication is characterized by specific abnormalities of movement coordination and visual attention but normal performance of complex cognitive functions. Saccade abnormalities suggest disruption of cerebellar and GABAergic functions.
Adult↗
Saccade and cognitive function in chronic kava users.
Kava is an extract from the Piper methysticum Forst. f. plant that has been consumed in the Pacific islands for millennia and more recently, among indigenous populations, in northern Australia and throughout the Western world as an herbal medicine. Through alterations on neuronal excitation, kava induces muscle relaxation, anasthesia, and has anxiolytic properties. There have been several isolated reports of psychotic syndromes, severe choreoathetosis and possible seizures following kava use. However, there is no conclusive evidence that kava interferes with normal cognitive processes. We tested a group of current, ex, and nonkava users among an indigenous population in northern Australia, using saccade and cognitive tests that have proven cross-cultural validity and are sensitive to subtle disruptions of the brain arising from substance abuse or neuropsychiatric illness. Despite collecting data from among the heaviest reported kava drinkers in the world, we found no impairment in cognitive or saccade function in individuals who were currently heavy kava users (and had been for up to 18 years), nor was there any impairment in individuals who had been heavy kava users in the past but had abstained for longer than 6 months. Current and ex-kava users showed a higher rate of kava dermopathy, lower body mass index, lowered blood lymphocytes and, in addition, current kava users showed elevated liver enzymes. While there has recently been increasing concern about potentially fatal liver damage attributed to kava use, we have found no evidence of brain dysfunction in heavy and long-term kava users.
Adolescent↗