Augmenting Computerized Cognitive Training With Vortioxetine for Age-Related Cognitive Decline: A Randomized Controlled Trial

Abstract

Objective: Age-related cognitive decline, the deterioration in functions such as memory and executive function, is faced by most older adults and affects function and quality of life. No approved treatments exist for age-related cognitive decline. Computerized cognitive training has been shown to provide consistent albeit modest improvements in cognitive function as measured by neuropsychological testing. Vortioxetine, an antidepressant medication, has putative procognitive and proneuroplastic properties and therefore may be able to augment cognitive training. In this placebo-controlled study, the authors tested the cognitive benefits of vortioxetine added to cognitive training for adults age 65 or older with age-related cognitive decline.

Methods: After a 2-week lead-in period of cognitive training, 100 participants were randomly assigned to receive either vortioxetine or placebo in addition to cognitive training for 26 weeks. The primary outcome measure was global cognitive performance, assessed by the NIH Toolbox Cognition Battery Fluid Cognition Composite. The secondary outcome measure was functional cognition, assessed by the UCSD Performance-Based Skills Assessment. All participants received motivational messaging and support from study staff to maximize adherence to the training.

Results: Participants who received vortioxetine with cognitive training showed a greater increase in global cognitive performance compared with those who received placebo with cognitive training. This separation was significant at week 12 but not at other assessment time points. Both groups showed improvement in the secondary outcome measure of functional cognition, with no significant difference between groups.

Conclusions: Vortioxetine may be beneficial for age-related cognitive decline when combined with cognitive training. These findings provide new treatment directions for combating cognitive decline in older adults.

Trial registration: ClinicalTrials.gov NCT03272711.

Keywords: Antidepressant; Cognitive Decline; Cognitive Interventions; Cognitive Training; Combination Strategies; Neuroplasticity.

Figures

Figure 1:

CONSORT Diagram

Figure 2:. Improvement in global cognitive performance with cognitive training + vortioxetine, compared to cognitive training + placebo, over 26 weeks of randomized intervention.

The figure shows greater improvement, as measured by the NIH Toolbox Cognitive Battery, in the vortioxetine + cognitive training group, which was significant in the overall model. For specific timepoints, the vortioxetine:placebo difference was significant at week 12 (+4.19 favoring vortioxetine [SE 1.52], p=0.0063, effect size [Cohen’s d]=0.57), but not at week 4 (+2.53 [SE 1.49], p=0.091, effect size=0.34) or at week 26 (+1.54 [SE 1.57], p=0.33, effect size=0.21). All reported effect sizes are with the change scores.