Schizophrenia Battery
Cantab Schizophrenia Battery A c c e l e r a t e t h e d e v e l o p m e n t o f s a f e a n d e f f e c t i v e m e d i c i n e s Fast, reliable and highly sensitive, the Cantab Schizophrenia Battery allows accurate quantification of cognitive effects when testing investigational drugs for Schizophrenia. Motor and mental response speed Visual learning and memory Planning Executive function Recognition memory Reaction Time (RTI) Paired Associates Learning (PAL) Stockings of Cambridge (OTS) Verbal Recognition Memory (VRM) Attention / reaction time Mnemonic Executive function Cognitive flexibility Emotional processing Rapid Visual Information Processing (RVP) Spatial Working Memory (SWM) Intra/Extra- Dimensional Shift (IED) Emotional Recognition Task (ERT)
Percent passing each stage (IED) Sensitive to cognitive impairment in schizophrenia and its prodrome Maximize scope for detecting cognitive benefits of intervention, and enrich samples, with large baseline deficits in schizophrenia Graded task difficulty enables robust detection of cognitive impairment even in first-episode of schizophreniform illness 2 Planning Executive Function (OTS) significant clinical impairment 00 95 90 First episode schizophrenia Healthy Controls Mnemonic Executive Function (SWM) greater impairment 85 80 greater impairment 75 Associative learning (PAL) 0 2 3 Impairment (Z-Score) vs Controls 70 Task stage increasing task difficulty IED impairment also correlates with duration of untreated illness (p=0.0) 2 Calculated from Hutton et al., Psych Med, 998; see also Aleman et al., Am J Psych, 999 & Liu et al., Schiz Res, 20;. 2 Joyce et al., B J Psych, 2002; see also Barnett et al., Neurosci Biobeh Rev, 200.
Composite CANTAB Score Objective measures that are clinically relevant and superior to alternative tests CANTAB predicts day-to-day function in schizophrenia better CANTAB Schizophrenia performance Highly significant correlation between CANTAB and everyday functioning (p<0.00) better everyday function CANTAB also predicts subjective cognitive complaints, quality of life, community functioning, and extent of negative symptoms, in schizophrenia 2 Everyday functioning (UPSA-2 total score) Baker et al., poster at International Society for CNS Trials and Methodology, 203. 2 e.g. Prouteau et al., Schiz Res, 2004; Prouteau et al., Psych Res, 2004; Zhornitsky et al., 203; Saleem et al., J Psychopharm, 204. UPSA = University of California San Diego Performance-based Skills Assessment
PAL errors Firm scientific grounding for hypothesis testing and dissemination of results Front of brain CANTAB OTS test is sensitive to frontal lobe dysfunction in schizophrenia Healthy Volunteer Normal frontal activation as expected (red) CANTAB PAL test impairment correlates with hippocampus volume loss in schizophrenia (p=0.00) 2 30 worse PAL performance Front of brain At rest During OTS Schizophrenia Failure of frontal activation 20 smaller hippocampus 0 4200 3600 3000 Hippocampus volume in schizophrenia (mm 3 ) At rest During OTS Andreasen et al., Arch Gen Psych, 992 2 Keri et al., Neuropsychologia, 202
Sustained attention (RVP) Enhanced early decision -making using cognition as a biomarker CASE STUDY Pro-cognitive effect of tropisetron (alpha-7 nicotinic acetylcholine receptor partial agonist / 5- HT3 antagonist) following 8-week treatment in just N=2 patients with schizophrenia (nonsmokers). Clinical measures were insensitive with this small N * p < 0.00 improvement Beneficial effects of tropisetron on symptoms of Schizophrenia were identified in a larger subsequent clinical trial 2 Baseline 8-weeks Shiina et al., Ann Gen Psych, 200; 2 Noroozian et al., Psychopharm, 203
Errors (SWM) Errors (PAL) Detect procognitive effects of treatment and make informed dose selection decisions CASE STUDY Cognitive improvement versus placebo following 22-week minocycline augmentation (antiinflammatory/anti-microbial) in Schizophrenia (N=54) CASE STUDY Selective cognitive improvement following 4-week SAM-53 treatment (5-HT6 antagonism) at 3mg/day in prototypical cognitive disorder (Alzheimer s Disease, N=74) 2 60 55 50 45 40 35 30 25 20 * p < 0.05 Week -2 Week 0 Week 22 Minocycline + atypical antipsychotics Placebo + atypical antipsychotics better performance 20 5 0 5 0-5 -0 * p < 0.05 Improvement Placebo 0.5mg.5mg 3mg 5mg Deterioration CANTAB PAL Levkovitz et al., J Clin Psych, 200 2 Brisard et al., ICAD conference, 200
Change in PAL total errors adjusted Early and sensitive detection of safety signals, including effects not predicted by animal models CASE STUDY: Contrary to expectations from animal models, acute treatment with higher dose alpha-5ia (GABA-A receptor subtype inverse agonist) impaired PAL in healthy volunteers (Phase efficacy study) CASE STUDY: CANTAB detects unwanted synergistic interactions between schizophrenia-relevant compounds, and can highlight equivalence (such as to blood alcohol concentrations [BAC]) 2 40 35 * p < 0.05 Deterioration equivalent to BAC>0.% 30 25 Deterioration 20 5 0 5 0 Placebo 2mg 4mg equivalent to BAC>0.05% Atack, Pharmacol Ther, 200 2 Internal Camcog data
Cantab Solutions The world s leading cognitive assessments Schizophrenia Battery Touchscreen assessment system for smaller, faster, more accurate trials Sensitive to cognitive impairment even at early stages of the disorder Detects efficacy signals where other measures fail Early and sensitive detection of safety signals Enhances decision-making in clinical trials using cognition as a biomarker
Chicago 225 York Road, Suite 20 Oak Brook Illinois, 60523 USA Tel: + 32 724 870 Cambridge Tunbridge Court Bottisham Cambridge, CB25 9TU UK Tel: +44 223 80700 Contact clinicaltrials@camcog.com Visit www.cantab.com/clinicaltrials Cambridge Cognition 204. All rights reserved. CTIS Schizophrenia v..4.4