THINC-it® a game changer in depression-related cognition

We have for a long time been looking for a practical way of evaluating cognitive dysfunction in depression. Now we have it. In the validation study of the new assessment tool, THINC-it®, 43% of patients with depression defined by DSM-5 had cognitive function that was at least one standard deviation below that of healthy controls. And 79% were functioning at or below 0.5 standard deviations from the norm. These are clinically significant differences.

So the new tool efficiently detects the problem. In the words of Bernhard Baune, of the University of Adelaide, Australia, its availability represents “a milestone” in efforts to measure and treat cognitive dysfunction.

A milestone in measuring cognition

The validation study involved 100 adult outpatients from the Toronto area of Canada and 100 healthy controls matched for age, sex and education. Their average age was 41, and 58% were women. The average MADRS score of patients was 33, indicating moderate to severe depression.

More than 80% of healthy controls performed better on this measure than patients with depression. In controls, scores were stable with time. So there is little doubt that THINC-it® can evaluate cognitive dysfunction, which was its first intended role.

The major question now is whether it is able to detect changes in response to treatment. A study that will provide the answer is in the advanced stages of planning.

Why should we assess cognitive function?

We need the cognition equivalent of a sphygmomanometer

Patients with an acute episode of major depression have cognitive deficits on a range of objective neuropsychological tests. The effect size of -0.5 to -0.8 compared to healthy controls is generally recognised as clinically significant, Raymond Lam, (University of British Columbia, Vancouver, Canada) told the meeting.

More than half of all depressed patients say that cognitive difficulties interfere with their work. The extent of cognitive dysfunction is greater with early onset of depression, with greater severity of symptoms, with longer duration, and with number of episodes. Comorbidities such as congestive heart failure or diabetes also play a part.

The full neuropsychology test battery is the gold standard assessment, but takes 4-5 hours to complete.  Self-report measures are more feasible in busy clinics. Subjectively reported symptoms correlate poorly with objective tests, but they reflect the way patients rate their functioning in real-life settings and so provide relevant information.

Ideally, we need both objective and subjective measures. The five-item version of the Perceived Deficits Questionnaire (PDQ-5) has been validated in depression, takes only a minute to complete, and relates to overall functional impairment – as assessed by the Sheehan Disability Scale, which includes work, social and family life. Crucially, the predictive value of the PDQ cognition measure is independent of depression severity.

So it is no surprise that the PDQ-5 for depression is included in the THINC-it® battery.

Atoms of cognition

The other elements that contribute to the THINC-it® tool were explained further by John Harrison (VU University Medical Center, Amsterdam, and Metis Cognition Ltd, UK).

Assessment is about tests that are good and not whether they are done with pencil and paper or with a computer, he said. But the fact is that all of the THINC-it® elements are computerised and self administered. Although designed as a screening tool, its components have been chosen because each has proven ability to identify change over the course of disease and its treatment.

So, in addition to the PDQ, we have the Spotter task, which is essentially choice reaction time; and the Symbol Check, based on the one-back test of working memory; Code Breaker – derived from the Digit Symbol Substitution Test; and Trails, based on Trail Making Test B. The entire package can be completed in around ten minutes. And it meets the requirements of being reliable, in the sense that similar results are obtained with repeat administration at the same point in time, and valid – in that it measures what we want it to – and appropriate for long-term use, since practice effects are small.

According to preliminary data from the Adelaide CoFaMS study, scores on the THINC-it® tool -- and on several of its individual components – are significantly different in currently depressed patients, those in remission, and healthy controls. The capacity to differentiate between these populations is added evidence of validity, Bernhard Baune suggested.

Now we need implementation

Cognition mediates health outcomes in depression, but also has implications for healthcare and health economics, Roger McIntyre (University of Toronto, Canada) told the meeting. Cognitive dysfunction is prevalent, persistent, progressive, and relevant to outcomes that are important to patients.

The THINC-it® tool should therefore be broadly welcomed and applied. But many inventions in medicine – however good in principle -- are not implemented. We have to recognise that, Dr McIntyre warned, and we have to make sure that the promise of THINC-it is realised.

The tool is free to download at http://thinc.progress.im/en