Targeting Cognitive Control Deficits With Neuroplasticity-Based Computerized Cognitive Remediation in Patients With Geriatric Major Depression: A Randomized, Double-Blind, Controlled Trial

Abstract

Late life major depression (LLD) is often accompanied by cognitive deficits. When patients have specific deficits in cognitive control functions (CCD), they are not only distressing and debilitating, they often predict poor clinical outcomes such as reduced response to SSRI/SNRI antidepressants, increased disability, suicide and all-cause mortality. We recently reported that in an open label trial, our treatment designed to target these specific CCD with neuroplasticity-based computerized cognitive remediation (nCCR) improved depression and CCD in patients who failed to remit with conventional antidepressant treatment. This study tested the hypothesis that in patients with LLD who have failed at least one trial of an SSRI/SNRI antidepressant at an adequate dose for at least 8 weeks, nCCR will improve both depressive symptoms and the CCD associated with poor antidepressant response (i.e. semantic strategy, inhibition of prepotent responses) more than an active control group. Participants were randomized (1:1) to receive either 30 hours/ 4 weeks of neuroplasticity based computerized cognitive remediation (nCCR) designed to target CCD, or the active control condition matched for duration, engagement, reward, computer presentation, and contact with study staff. All participants and raters were blinded. Mixed effects model analysis the time effect (week) (F(1,71.22)=25.2, p<0.0001) and treatment group X time interaction (F(1,61.8)=11.37, p=.002) reached significance indicating that the slope of decline in MADRS was steeper in the nCCR-GD group. Further, the nCCR group improved their semantic clustering strategy(t(28)=9.5; p=.006), as well as performance on the Stroop interference condition, and cognitive flexibility (Trails B). Further, results transferred to memory performance, which was not a function trained by nCCR. clinicaltrials.gov.