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Pietrzak R.H.,Yale University | Pietrzak R.H.,Cogstate Ltd | Snyder P.J.,Brown University | Snyder P.J.,Yale University | And 2 more authors.
Schizophrenia Research | Year: 2010

Background: Amelioration of cognitive impairment is an important treatment goal for a broad range of neuropsychiatric disorders, including schizophrenia. One critical issue in clinical trial design is the extent to which repeated exposure to cognitive tests (i.e., practice effects) may lead to improvement in performance on the cognitive tests in the absence of any true treatment effect. The current study examined the extent to which practice effects on a measure of executive function may influence the sensitivity of that task to detecting the cognitive-enhancing effects of a single acute dose of d-amphetamine in individuals with chronic schizophrenia. Methods: Twenty-four men with chronic schizophrenia were randomized to receive a constant or random/matched alternate form version of a hidden maze learning measure of executive function (Groton Maze Learning Test; GMLT) on four separate occasions in one month. They also completed a measure of psychomotor speed. Using a double-blind, placebo-controlled, parallel groups design, cognitive function following administration of a single dose of d-amphetamine (20 mg p.o) or placebo was then assessed. Results: The group who received the constant-pathway version of the GMLT showed a large practice effect (d = 2.05) over four practice sessions. Consequently, they did not evidence any improvement on the GMLT following d-amphetamine administration. In contrast, the group who received the random/matched alternate version of the GMLT showed a statistically significant and large effect size (d = .84) improvement on this measure. Both groups showed d-amphetamine-related improvement on a measure of psychomotor speed. Conclusions: Results of this study suggest that practice effects associated with repeated exposure to a cognitive test could obscure the sensitivity of the test to detecting true treatment-related cognitive improvement. © 2010. Source

Harvey P.D.,University of Miami | Siu C.O.,Data Power DP Inc. | Hsu J.,Sunovion Pharmaceuticals | Cucchiaro J.,Sunovion Pharmaceuticals | And 2 more authors.
European Neuropsychopharmacology | Year: 2013

This double-blind study evaluated change in cognitive performance and functional capacity in lurasidone and quetiapine XR-treated schizophrenia patients over a 6-week, placebo-controlled study, followed by a 6-month, double-blind extension. Cognitive performance and functional capacity were assessed with the CogState computerized cognitive battery and the UPSA-B. Analyses were conducted for all subjects, as well as the subsample whose test scores met prespecified validity criteria. No statistically significant differences were found for change in the composite neurocognitive score for lurasidone (80. mg/day and 160. mg/day) groups, quetiapine XR and placebo in the full sample at week 6. For the evaluable sample (N=267), lurasidone 160. mg was superior to both placebo and quetiapine on the neurocognitive composite, while lurasidone 80. mg, quetiapine XR, and placebo did not differ. UPSA-B scores were superior to placebo at 6 weeks for all treatments. In the double-blind extension study, analysis of the full sample showed significantly better cognitive performance in the lurasidone (40-160. mg) group compared to the quetiapine XR (200-800. mg) group at both 3 and 6 months. Cognitive and UPSA-B total scores were significantly correlated at baseline and for change over time. This is the first study to date where the investigational treatment was superior to placebo on both cognitive assessments and a functional coprimary measure at 6 weeks, as well as demonstrated superiority to an active comparator on cognitive assessments at 6 weeks and at 6 months of extension study treatment. These findings require replication, but are not due to practice effects, because of the placebo and active controls. © 2013 Elsevier B.V. and ECNP. Source

Dingwall K.M.,Charles Darwin University | Maruff P.,University of Melbourne | Maruff P.,Cogstate Ltd | Fredrickson A.,Cogstate Ltd | Cairney S.,Charles Darwin University
Drug and Alcohol Dependence | Year: 2011

Background: Cognitive impairment reflecting CNS disruption in chronic solvent abusers can resolve within two years of abstinence. However, the specific time course for recovery has yet to be determined empirically. This study monitored cognition among solvent (i.e., gasoline) abusers throughout 8 weeks of residential treatment. It also investigated the extent to which solvent-related cognitive impairments persisted following discharge. Methods: Non-drug using healthy controls (n= 33) and solvent abusers (n= 29) who had inhaled gasoline, regularly or episodically, for an average of 4.3 years (SD = 2.7) were assessed. Using linear mixed model analyses, solvent abusers were compared to healthy controls throughout treatment at baseline, two weeks, four weeks and six weeks, on visual motor, attention, learning, memory, and executive function tasks. Ten users who maintained abstinence were reassessed an average of 12 months later (SD = 2.8) and were compared to healthy controls (n= 12) retested at the same time interval using ANCOVA while controlling for age and baseline performance. Results: At baseline, solvent abusers showed cognitive deficits on visual motor, learning and memory, paired associate learning, and executive functions. Paired associate learning performance improved within 6 weeks of abstinence, however, impairments in visual motor speed, learning and memory, and executive function persisted throughout and in some cases beyond treatment. Conclusions: Cognitive deficits exist for solvent abusers upon treatment entry. Some impairments resolve within weeks of abstinence, while memory and executive function improves gradually over months to years of abstinence, and might never fully recover. © 2011 Elsevier Ireland Ltd. Source

Pietrzak R.H.,Yale University | Pietrzak R.H.,Cogstate Ltd | Snyder P.J.,Brown University | Snyder P.J.,Yale University | And 2 more authors.
Human Psychopharmacology | Year: 2010

There is general agreement that pharmacologic improvement of cognition in chronic schizophrenia is a worthwhile therapeutic goal. Accordingly, there has been careful consideration about how neuropsychological methods can be used to detect improvement in cognition in people with schizophrenia. However, little data are available on the nature and magnitude of cognitive improvement that can occur with adjunctive therapeutic interventions. This double-blind, placebo-controlled crossover study examined the nature and magnitude of cognitive enhancement associated with a single-dose administration of d-amphetamine in 32 adult men with schizophrenia using a set of tasks developed specifically for detecting treatment-related change in cognitive function. Relative to placebo, acute d-amphetamine administration was associated with clinically meaningful improvement on measures of executive function and visual attention and vigilance, and with modest improvements on a measure of speed of processing. These results suggest that a brief computerized cognitive test battery designed for repeat administration, in combination with a statistical approach that emphasizes individual-level change, provides a sensitive approach to detecting the effect of cognitive-enhancing medications in people with chronic schizophrenia. Copyright © 2010 John Wiley & Sons, Ltd. Source

Cromer J.R.,University of Connecticut | Cromer J.A.,The Picower Institute for Learning and Memory | Cromer J.A.,Massachusetts Institute of Technology | Maruff P.,Cogstate Ltd | And 2 more authors.
Experimental and Clinical Psychopharmacology | Year: 2010

Several psychological constructs (e.g., subjective perception of intoxication, visuomotor speed) display acute tolerance to alcohol, that is, show improvement at declining blood alcohol concentrations (BACs) relative to equivalent rising BACs. However, methodological challenges emerge when attempting to make such comparisons across limbs of the BAC curve, which have proven a barrier to advancing research on acute tolerance. To date, no studies have made multiple comparisons across the entire BAC trajectory. This study employs experimental procedures that overcome some of these difficulties, offering a clearer picture of recovery of impairment for subjective perception of intoxication and cognitive performance and the relationship between them. Twenty participants were assessed at multiple time points over 2 days. Continuous subjective perception of intoxication ratings and cognitive data derived from a computerized measure were paired with a novel analytic paradigm, which allowed comparisons at identified BACs. Results showed acute tolerance for individuals' subjective perception of intoxication and for performance on cognitive tasks measuring visuomotor speed and learning efficiency (recovery from impairment). In contrast, performance on measures of executive function and short-term memory showed no significant difference between limbs at exact concentrations (no recovery from impairment). Therefore, despite participants feeling less intoxicated over time, many cognitive functions remained impaired. The implication for these findings in terms of drunken driving behavior are substantial, suggesting that people may be likely to drive once they subjectively perceive that they have recovered from the acute intoxicating effects of alcohol, despite the persistence of " higher order" cognitive impairments. © 2010 American Psychological Association. Source

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