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Enhancing Cognition Enhancing Cognition Professor Barbara J Sahakian DSc FMedSci Member of the World Economic Forum Global Agenda Council for Brain Research Member of the Human Brain Project President of the International Neuroethics Society University of Cambridge Department of Psychiatry and MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute We need cognitive enhancing drugs to treat the cognitive disability of people with mental health disorders and brain injury • Disorders such as attention deficit Estimated Total Annual Costs hyperactivity disorder (ADHD), including health service costs, lost earnings, lost schizophrenia and Alzheimer’s disease productivity and human costs all have associated cognitive problems Depression £20.2-23.8 billion Anxiety £8.9 billion • Cognitive enhancing drugs (Smart Drugs) are needed to treat cognitive Schizophrenia £13.3 billion disabilities and improve functional Dementia £17 billion outcome, quality of life and wellbeing for people with neuropsychiatric Somatisation disorder £17.6 billion disorders and brain injury. - Department of Health (2011) No health without mental health: The economic case for improving efficiency and quality in mental health - The Conversation : http://theconversation.com/burden-of-brain- disorders-ignored-by-government-16641 - Fineberg, Haddad, Carpenter, Gannon, Sharpe, Young, Joyce, Rowe, Wellsted, Nutt, Sahakian (2013) Journal of Psychopharmacology Some Possible Methods of Boosting Your Brain Power • Pharmacological (Smart Drugs) Learning helps to generate new brain cells • Neuroprosthetics for cognition New brain cells in control • Devices (eg tDCS, TMS) • Education ‘New’ brain cells after • spatial learning Cognitive training/ Brain training • Physical exercise Gould et al (2000) Nature Neurosci Voluntary exercise leads to an increase in - Cognitive Enhancement – Special Issue of Current Opinion in overall neurogenesis Behavioral Sciences (http://www.sciencedirect.com/science/journal/23521546/4) - Beddington, Cooper, Field, Goswami, Huppert, Jenkins, Jones, Kirkwood, Sahakian & Thomas (2008) ‘The mental wealth of nations’ Nature, 455 In rats, after 2-3 weeks of access to an exercise wheel, the number of BrdU positive cells (a DNA precursor) Neurogenesis has almost doubled after 28 days Control Voluntary Enriched Exercise Environment Olson et al (2006) Hippocampus Eadie et al (2005) J Comp Neurol Action of Methylphenidate, Modafinil, and Atomoxetine Stimulated vigilance Calm wakefulness Methylphenidate (Ritalin) increases synaptic concentration of dopamine and noradrenaline by blocking their reuptake. Atomoxetine (Strattera) is a relatively selective noradrenaline reuptake inhibitor (SNRI). Stahl SM (2002) J Clin Psychiatry Modafinil (Provigil) action is unclear; Possibilities Neuroscience-based nomenclature include: indirect mediation of ACh and/or (Zohar et al, 2014) classifies Adrenergic alpha –1 receptor activity. Appears to modafinil as a dopamine reuptake effect hypothalamic orexin and histamine, and has inhibitor. a small effect on dopamine transporter activity. Recent evidence suggests NA (Minzenberg et al http://www.ecnp.eu/~/media/Files/ecn 2008), DA (Volkow et al 2009) and glutamatergic p/Projects%20and%20initiatives/Nome mechanisms (Scoriels, Jones, Sahakian 2013). nclature/Review%20articleNEUPSY_10 717v2%20pdf.pdf Using Innovative Technology to Assess Cognition, Including Working Memory Invention •CANTAB was co-invented by Trevor Robbins and Barbara Sahakian •CANTAB computerised tests which use a touch- sensitive screen. •Used in over 500 universities, research institutes and hospitals in over 50 countries • Validated by over 1,200 peer-reviewed publications “I see it in the extraordinary work of UK life sciences companies, like Ixico, Cambridge Cognition, Psychology Online and Proteome Sciences, working with others to develop new tests for Alzheimer’s Disease.” -- Prime Minister David Cameron’s G8 Speech, 11 December 2013 www.cantab.com www.cantabmobile.com www.camcog.com The importance of working memory for academic achievement • Working Memory is related to fluid and crystallized intelligence Friedman, Miyake et al (2006) Psychological Science Working Memory • Working memory is a key process for most executive function tasks, such as planning and problem solving • Correlational studies supported a close relationship between WM and measures of fluid intelligence and science achievement Yuan et al (2002) Educational Research Review • Working memory at the start of formal education is a more powerful predictor of subsequent academic success than IQ Alloway and Alloway (2010) J Exp Child Psychol Working memory is affected in many neuropsychiatric disorders, including ADHD and schizophrenia CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) CANTAB Spatial Working Memory (SWM) Look for a blue token hidden in one of the boxes, without returning to a box where a token has previously been found. Cambridge Cognition (www.camcog.com) Neuroimaging at the Wolfson Brain Imaging Centre Working memory is impaired Methylphenidate improves spatial in adult patients with ADHD working memory performance in adult patients with ADHD 10 40 8 30 6 20 * 4 Improvement Better Performance Better 10 2 Between search errors,6-box stage 0 0 Control ADHD Drug Placebo McLean, Dowson, Toone, Young, Bazanis, Turner, Blackwell, Dowson, McLean, Sahakian Robbins, Sahakian (2004) Psych Med (2005) Psychopharm Methylphenidate (Ritalin) improves working memory & increases ‘efficiency’ of dorsolateral prefrontal cortical network in healthy volunteers Improvement Elliott, Sahakian, Matthews, Bannerjea, Rimmer, Robbins (1997) Psychopharm Mehta, Owen, Sahakian, Mavaddat, Pickard, Robbins (2000) The Journal of Neuroscience Modafinil improves working memory in healthy volunteers and in patients with first episode psychosis Healthy Volunteers Patients with First Episode Psychosis Improvement Improvement Müller, Rowe, Rittman, Lewis, Robbins, Sahakian (2013) Scoriels, Barnett, Soma, Sahakian, Jones Neuropharmacology (2011) Psychopharmacology Modafinil also has effects on ‘hot’ cognition It improves emotional processing in first episode psychosis happiness Improvement Scoriels, Barnett, Murray, Cherukuru, Fielding, Cheng, Lennox, Sahakian and Jones (2011) Biological Psychiatry EMOTICOM (CANTAB for ‘hot’ cognition) Domains: • Emotional Processing • Social Cognition • Impulsivity • Motivation and Reward 200 Healthy Volunteers Tested MRC funded research: R Elliott, BJ Sahakian, TW Robbins, J Roiser, M Mehta With Amy Bland and Thea Schei Rise in prescription for Methylphenidate (Ritalin) in England. Increase of 56% in the past 5 years (Care Quality Commission). It is no longer caffeine but pills to which a rising number of students turn when revising “The prescribing of methylphenidate has “Prof Sahakian is regularly approached continued to increase in both the NHS and by students who say they feel under private sectors. This is likely to be pressure to take the drugs for fear of attributable to its use in the management falling behind their peers. ” of childhood and adult ADHD and, due to 13 August 2013 its potential for diversion, and misuse, its use should also be monitored carefully.” Increasing Lifestyle Use of ‘Smart Drugs’ by Healthy People Study % of People Using Smart Drugs Nature 20% Varsity
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