Targeting cognitive control deficits with neuroplasticity-based computerized cognitive remediation in patients with geriatric major depression: A randomized, double-blind, controlled trial

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Importance

Late life depression 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 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. Here we test nCCR against a computerized, but non-CCD-targeted,
expectancy-matched control. Our hypothesis is that participants receiving nCCR will
have greater improvement in both mood and CCD after four weeks of treatment.

Objective

This study tested the hypothesis that in patients 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 cognitive control functions associated with
poor antidepressant response (i.e. semantic strategy, inhibition of prepotent responses)
more than an active control group. We also explored whether training in cognitive
control functions would “transfer” benefit to related functions that rely on intact
cognitive control such as working memory, cognitive flexibility, and long delay memory.

Design

A pilot randomized, controlled, double-blind trial of four weeks (30 hours) of nCCR
against an active control condition matched for duration, engagement, reward, computer
presentation, and contact with study staff. Ratings and neuropsychological measures
were taken by trained research staff, unaware of study hypotheses, and blinded to
treatment condition.

Setting

Weill Cornell Institute of Geriatric Psychiatry, an outpatient research clinic at
an academic medical center.

Participants

Older adults (60-89) with major depressive disorder MDD (by SCID-R/DSM-IV), who failed
to achieve remission (Montgomery-Asberg Depression Rating Scale, MADRS >15) after
treatment with therapeutic dosages of an SSRI or SNRI for at least 8 weeks. 36 of
42 patients entered the study. Of the 36 patients, 30 completed the four-week trial.

Interventions

Participants were randomized (1:1) to receive either neuroplasticity based computerized
cognitive remediation (nCCR) designed to target CCD, or the active control condition.
All participants and raters were blinded to their treatment assignment.

Main Outcome Measures

Mood: MADRS; Disability: WHODAS-II; CCD: semantic clustering; CVLT ii; Stroop CW;
Trails B, design fluency, and digits backward were administered at baseline, and at
the end of four weeks of treatment.

Results

The sample was 63.6% female, 36.4% male (mean age=73.5 years; sd=7.8). Mixed effects
model analysis groupxtime interaction reached significance (F(1,61.8)=11.37, p=.002)
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.

Conclusions

Results indicate that nCCR improves depression and CCD in elderly patients refractory
to other treatments more than a control condition.

clinicaltrials.gov

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