We found that intensive computer-based cognitive training is feasible in at least a subgroup of people with MCI. Seventy-seven percent of subjects completed the training, even though it involved a substantial time commitment of 90-100 minutes/day, 5 days/week for 6 weeks. Although most subjects in our study were highly educated, some had not previously used a computer.
For our primary outcome of global cognitive function as measured by the RBANS total score, we observed an effect size of 0.33 SD, which is similar in magnitude to cholinesterase inhibitors (ChEIs) for treatment of Alzheimer's disease (35
). Although this effect was not statistically significant, its size suggests that a larger trial may be warranted. A sample size of 145 subjects per group would be required to detect this effect size with two-sided alpha = 0.05 and 80% power.
For our secondary outcomes, although most differences between the intervention and control groups were not statistically significant, we observed a pattern in which effect sizes for measures of verbal learning and memory consistently favored the intervention, which we had hypothesized a priori. This is consistent with an RCT of a related Posit Science program that was studied in healthy elders, in which significant improvement was observed in auditory memory, especially in subjects who started out with scores below the mean (36
). In contrast, effect sizes for measures of language and visuospatial function tended to favor the control condition, which involved listening to books, reading and playing the visuospatially-oriented computer game Myst. This pattern is consistent with the hypothesis that these training programs may have domain-specific effects. Larger studies are needed to determine whether these observations are real or due to random variation.
Interestingly, the largest effect size was observed on the Spatial Span test, which requires subjects to remember the location of different items on a spatial grid. Although we did not hypothesize a priori that this test would be particularly sensitive to our intervention, in retrospect, the Spatial Span test is similar to the fourth exercise in our intervention, in which subjects must remember the location of sounds on a spatial grid in order to match them. However, additional studies are needed to determine whether this finding reflects a true effect or whether it was due to chance.
Most prior RCTs of cognitive training interventions in older adults with MCI have been relatively small (≤100 subjects), and results have been mixed. Several studies have found that memory training improves subjective but not objective memory measures. In a study of 54 elders with amnestic MCI, Troyer et al. (37
) found that those who received training in practical, everyday memory techniques increased knowledge and use of memory strategies but not memory test performance compared to a waitlist control group. Similarly, Rapp et al. (22
) found that memory training improved perceptions of memory capabilities but not objective measures of memory performance compared with a no-training control group. It remains unclear whether these negative findings are real or due to low statistical power.
Several other studies have reported that various cognitive training programs are associated with significant improvements in cognitive outcomes, but they have suffered from various methodological limitations that make interpretation of results more difficult. One study did not include a control group (23
), another study included a control group but did not randomize study participants (21
), and several studies did not report between-group comparisons (24
). For example, in a study of 59 elders with MCI, Rozzini et al. (25
) found that the participants who received neuropsychological training plus ChEIs experienced significant improvements in measures of memory, abstract reasoning, mood and behavioral symptoms whereas those who received ChEIs alone improved only in depressive symptoms and those who received no treatment experienced no changes, but differences between the groups were not reported. Another study that included 84 elders with MCI or mild to moderate AD found that those who received a cognitive-motor plus psychosocial support intervention experienced stabilization of cognitive status over the first 6 months of the study compared to significant decline in the group that received psychosocial support alone, but between group differences for cognitive measures appear to have been non-significant.(24
) Taken together, our results combined with the results from these other studies indicate that a larger trial with adequate statistical power is warranted.
Strengths of our study include evaluation of a novel, cognitive training intervention to enhance cognitive function in subjects with MCI, who are a vulnerable group with a high risk of developing dementia. Limitations include the small sample size, which restricts our ability to determine whether our findings are due to chance or lack of power. In particular, we examined 12 secondary outcomes measures and, using the p<0.05 criterion for statistical significance, one would expect one in 20 `statistically significant' findings to be false positives.
In addition, it is likely that our study population included primarily highly motivated subjects, and it is unclear whether our results would generalize to less motivated subjects. It is possible that our subjects were more compliant than other subjects, which could magnify the effects of our intervention. On the other hand, our subjects may have been engaging in higher levels of concurrent cognitively and physically stimulating lifestyle activities, which could have `washed out' the effects of our intervention. Future studies should determine the role that co-interventions may play on the results of cognitive training trials.
Finally, the active control utilized for our study may have been too active. We had hypothesized that the activities performed by the control group would be the equivalent of an inert placebo; however, our trial suggests that these activities also may have resulted in domain-specific cognitive improvements. Future studies should either include a no-contact control group (in a three-arm design) or confirm that any active control activities are, in fact, inert before commencing a trial.
In summary, we found that intensive computer-based mental activity training is feasible in elders with MCI and that larger trials are warranted.