Clinical Trial Measures Impact of Combining Cognitive Training with Drug Treatment in Age-Related Cognitive Decline

Clinical Trial Measures Impact of Combining Cognitive Training with Drug Treatment in Age-Related Cognitive Decline

Posted: May 7, 2020
Clinical Trial Measures Impact of Combining Cognitive Training with Drug Treatment in Age-Related Cognitive Decline

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A randomized clinical trial in patients with age-related cognitive decline found an advantage of cognitive training combined with a drug thought to boost cognition, compared with cognitive training alone.


Newly reported results of a randomized clinical trial indicate progress in the effort to help those over age 65 who are suffering from cognitive decline. Such decline is experienced by most older adults at some point, although the degree and type of impairment varies greatly among individuals.

A research team led by Eric Lenze, M.D., of Washington University, and Christopher Bowie, Ph.D., a 2013 BBRF Independent Investigator and 2007 and 2003 Young Investigator, at Queen’s University, Ontario, set out to discover if computer-delivered cognitive training would help patients more if accompanied by an FDA-approved antidepressant medicine that is thought to boost cognition. That drug is called vortioxetine. Results of the trial appeared in The American Journal of Psychiatry.

One hundred people over age 65 who were diagnosed with age-related cognitive decline were randomized in the clinical trial. All participants received 26 weeks of computer-guided cognitive training, as well as a 2-week training period that preceded the start of the trial. Once the 26-week trial began, half the participants took 10 mg of vortioxetine daily, while the other half took a placebo pill. Vortioxetine has demonstrated pro-cognitive effects in preclinical tests, as well as cognitive benefits in clinical trials that tested its effectiveness in depression. The observed impacts on cognition appeared to be independent of its effect on depression symptoms in those previous studies.

Vortioxetine is a serotonin reuptake inhibitor, but with effects that other widely prescribed drugs in the class such as Prozac or Lexapro do not have. Specifically, it is thought to interact differently with two variant types of neuronal receptors for serotonin, called the serotonin-3 and serotonin-7 receptors, possibly increasing neurotransmission in the dopamine, cholinergic, and histamine neurotransmitter systems.

The researchers measured cognitive functioning using a battery of cognitive tests for all study participants, at “baseline,” when the trial began, and at 4, 12, and 26 weeks during the intervention phase. The primary test used to assess the participants is called the NIH Toolbox Cognition Battery. Delivered via computer, it is able to assess performance in what the researchers term “fluid abilities.” This reflects participants’ ability to handle tasks related to skills in solving problems, thinking and acting quickly, and adapting to new situations. These areas are among those that deteriorate naturally with age.

The cognitive training program that all study participants received over 26 weeks was a software program called Scientific Brain Training Pro. Participants were instructed to use the program five times each week for 30 minutes a day. In the 2-week lead-in period before the start of the randomized trial, those who either had trouble adhering to the program or quickly reached a ceiling in their cognitive function were eliminated from the trial, in the interest of discovering its impact on typical users.

Results of the trial were modestly positive. The combination of the cognitive training software plus daily vortioxetine showed a clear statistical advantage overall and at the 12-week time point in the trial—but not at any of the other time points, including the end-point at 26 weeks.

Still, the team considers this result “important, because this is the first study, to our knowledge, to demonstrate that a putative pro-cognitive drug could be combined with cognitive training in age-related cognitive decline” to provide greater improvement than cognitive training alone.

Studies with more participants would add power to the results, the team said, and perhaps reveal whether the advantage of combined treatment is durable.

Further study might also address the question of whether any advantage of combined treatment was additive—the result of cognitive training and drug treatment each adding an increment of benefit; or interactive, with, for example, the drug “driving beneficial [brain] plasticity such that cognitive training is more efficient.” The researchers also want to know how the combination approach fares in patients whose cognitive decline is observed to progress over time, especially whether combined treatment slows such advance.