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THINC-it: what is it?

2016, European Neuropsychopharmacology

Cognitive dysfunction is an important aspect of major depressive disorder (MDD) [1,2]. The domains of executive function, working memory, attention and episodic memory are amongst those commonly affected [3], with cognitive performance diminished in the range of small (0.2) to medium (0.5) effect sizes in even first-episode MDD patients [4]. A variety of objective tests have been used to detect cognitive deficits in MDD. However, few of these tests are appropriate for the screening of cognitive deficits, as they are often overly time-consuming and deficient with respect to their reliability, sensitivity and validity [5]. Working memory is often assessed using the n-back task, attention by the Choice Reaction Time task, executive function by the Trail Making Test-B and general cognition by the Digit Symbol Substitution Test. These objective tests can be usefully supplemented by subjective data obtained from self-report assessments such as the 5-item version of the Perceived Deficits Questionnaire (PDQ-5). The need for a simple, well-validated screening tool to evaluate cognitive dysfunction in patients with MDD has led to the THINC Task Force developing the ‘THINC-it’ assessment. THINC-it is comprised of executive function, memory, attention and working memory measures that have been ‘gamified’, and are augmented with an on-screen version of the PDQ-5. THINC-it can be used on desktop and tablet computers, requires non-expert administration and yields simple data reporting. The different elements of THINC-it will be demonstrated during the presentation.

THINC-it: what is it? John Harrison Alzheimer Center, VU University Medical Center, West London Mental Health Trust, Metis Cognition Ltd Disclosures Associate Professor in the Alzheimer Center at the VU University Medical Center, Amsterdam Honorary Professor at West London Mental Health Trust Principal Consultant at Metis Cognition Ltd Consulting roles (past 2 years) AbbVie, Access to Quality, Amgen, Anavex, AstraZeneca, Avonex, Avraham, Axon, Axovant, Biogen Idec, Boehringer Ingelheim, Bracket, Cambridge Brain Sciences, Catenion, CRF Health, DeNDRoN, EnVivo Pharma, Enzymotec, ePharmaSolutions, Eisai, Eli Lilly, Forum Pharma, Fresh Forward, GfHEu, Heptares, Janssen AI, Johnson & Johnson, Kaasa Health, Kyowa Hakko Kirin, Lundbeck, MedAvante, Merck, MyCognition, Mind Agilis, Neurocog, Neurim, Neurotrack, Novartis, Nutricia, Orion Pharma, PharmaNet/i3, Pfizer, Prana Biotech, PriceSpective, Probiodrug, Prophase, ProStrakan, Regeneron, Reviva, Roche, Sanofi, Servier, Shire, Takeda, TCG, TransTech Pharma, Velacor Research or grants Memorabel Speaker Bureaus and CME activities Lundbeck, Medscape Royalties Oxford University Press, Blackwell Publishers Patents and share options MyCognition, Neurotrack Cognitive impairment in patients with depression Detection task Timed chase GMLT GMLTdelay ISLT ISLTdelay SECT Verbal fluency Stroop test Magnitude of impairment relative to control (d) 0.0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 Clinically relevant -1.0 GMLT, Groton Maze Learning Test; ISLT, International Shopping List Task; SECT, Social Emotional Cognition Test; d, Cohen’s d effect size Douglas KM et al. Br J Psychiatry 2011;198:115-22 Cognitive symptoms are common in depression Residual cognitive symptoms in between depressive episodes Cognitive symptoms during depressive episodes Proportion of time spent without cognitive symptoms Proportion of time spent without cognitive symptoms 44% 94% Proportion of time spent with cognitive symptomsa Proportion of time spent with cognitive symptomsa aAccording to Diagnostic and Statistical Manual of Mental Disorders 4th Edition: diminished ability to think or concentrate, or indecisiveness Prospective study (n=267) assessed 12 times over 3 years Conradi HJ et al. Psychol Med 2011;41:1165-74 https://www.youtube.com/watch?v=s3ZVRQp2ky0 THINC-it: a proposed solution ● 4 brief, reliable tests of ─ Global cognition ─ Attention ─ Working memory ─ Executive functions ● Non-expert administration ● Simple data reporting http://thinc.progress.im/en/content/thinc-it-about https://clinicaltrials.gov/ct2/show/NCT02508493 PDQ-D5 The following questions describe problems people may have with their memory, attention or concentration. Please select the best response based on your experiences during the past 7 days During the past 7 days, how often did you… Never in the past 7 days Rarely Sometimes Often Very often (once or twice) (3 to 5 times) (about once a day) (more than once a day) Have trouble getting things organised? 0 1 2 3 4 Have trouble concentrating on what you were reading? 0 1 2 3 4 Forget the date unless you looked it up? 0 1 2 3 4 Forget what you talked about after a telephone conversation? 0 1 2 3 4 Feel like your mind went totally blank? 0 1 2 3 4 PDQ-D5, Perceived Deficits Questionnaire for Depression, 5-item version Key domains: the atoms of cognition Episodic memory Executive functions Working memory Psychomotor speed Attention Social cognition Digit Symbol Substitution Test (DSST) Wechsler D. Manual for the Wechsler Adult Intelligence Scale – Revised. The Psychological Corporation, 1981; Taylor MA. The Fundamentals of Clinical Neuropsychiatry. Oxford University Press, 1999 Key domains: the atoms of cognition Episodic memory Attention Working memory Executive functions Best-practice guidance for assessment of cognition TESTS MUST BE… þ þ þ þ þ RELIABLE SENSITIVE VALID LONGITUDINAL USE CROSS–CULTURAL USE Harrison J, ‘Measuring the Mind: Detecting cognitive deficits and measuring cognitive change in patients with depression’, in McIntyre RS (ed.), Cognitive Impairment in Major Depressive Disorder, Cambridge, Cambridge University Press, 2016 Identifying vs monitoring cognitive dysfunction -3 SD Does the patient have cognitive dysfunction? Has there been a change in cognitive function? X X -2 SD -1 SD Abnormal 0 +1 SD +2 SD +3 SD Normal -3 SD -2 SD Decline -1 SD 0 +1 SD +2 SD +3 SD Improve Determining reliable change in individuals Test score 2 Requires the use of reliable tests Calculate test stability: within-subject standard deviation (WSD) Use WSD to plot the confidence interval around test score 1 Test score 1 No real change Test score 2 Confidence interval Mean Real change Summary and recommendations l Cognitive function can be impaired in patients with MDD l Selected measures must be reliable, sensitive and valid l THINC-it has been designed to meet ‘best practice’ guidance Thank you Email: [email protected] http://www.linkedin.com/in/drjohnharrison http://open.academia.edu/JohnHarrison @johncpc