A computer-based cognitive training program focused on speed of processing — reinforced with periodic booster sessions — reduced the risk for Alzheimer’s disease and related dementias (ADRDs) by 25% over 20 years, whereas memory and reasoning training showed no such benefit in the randomized controlled trial (RCT).

“Seeing that boosted speed training was linked to lower dementia risk two decades later is remarkable because it suggests that a fairly modest nonpharmacological intervention can have long-term effects,” Marilyn Albert, PhD, director of the Alzheimer’s Disease Research Center at Johns Hopkins Medicine in Baltimore, said in a statement.

“The cognitive speed training that was done twice a week for 5-6 weeks, with booster sessions a year later and then 3 years later. That’s not a lot. Yet the results were very clear and very dramatic,” Albert noted in an interview with Medscape Medical News.

Results of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial were published online on February 9 in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.

Adaptive and Implicit Learning

Launched in 1998, the ACTIVE trial enrolled 2802 community-dwelling adults aged 65 years or older and randomly assigned them to either one of three cognitive training programs focused on speed, memory, or reasoning or a control group that received no training.

The cognitive speed training was computerized and designed to improve the speed and accuracy of visual information processing, while expanding the visual area over which a person could pay attention and make rapid decisions.

It was adaptive and personalized, starting each participant at a task difficulty appropriate for their abilities, getting more challenging as they succeeded at the task, and getting easier when they struggled with the task.

The other two interventions — memory and reasoning training — were not computer-based but were delivered in structured group sessions led by an instructor. The memory training focused on improving verbal episodic memory through mnemonic strategies. The reasoning training focused on improving the ability to solve everyday problems that contain serial patterns.

Participants in the training groups completed up to 10 sessions of 60-75 minutes of cognitive training over 5-6 weeks. Those who completed at least eight sessions were re-randomized to receive booster sessions at 11 and 35 months after baseline.

When the three intervention groups were compared with the control group in the full sample, none of them showed a statistically significant reduction in the risk for dementia. The difference emerged when booster sessions were taken into account.

Participants randomly assigned to speed training who completed at least one booster session showed a statistically significant lower risk of being diagnosed with ADRDs than those assigned to the control group (hazard ratio [HR], 0.75), whereas those who received speed training without booster sessions showed no reduction in risk (HR, 1.01) over the follow-up period.

Neither memory nor reasoning training showed a significant effect on the risk for dementia, with or without booster sessions.

Albert said the “adaptive” nature of the speed training may be one reason it outperformed memory and reasoning training. The level of challenge was adapted for each participant’s individual performance level that day. People who were faster at the start moved to faster challenges quickly, and people who needed more time started at slower levels. The memory and reasoning programs were not adaptive — everyone in the group learned the same strategies.

Another reason may be that speed training involves “implicit learning” that involves acquiring knowledge and skills unconsciously, often by picking up patterns from experience, practice, or repeated exposure. In contrast, memory and reasoning training programs involve “explicit learning” that requires focused attention and typically involves direct instruction on how to do a task.

Caveats and Cautionary Notes

Reached for comment, Jessica Langbaum, PhD, senior director of research strategy at Banner Alzheimer’s Institute in Tucson, Arizona, told Medscape Medical News that the ACTIVE study “provides additional evidence of the beneficial effects of speed-of-processing training.”

“Staying cognitively engaged and taking part in cognitively stimulating activities is an important piece of overall brain health and should be part of broader recommendations along with other nonpharmacological activities (eg, exercise, nutrition),” said Langbaum, who wasn’t involved in the study.

She noted that data from both the U.S. POINTER and FINGER studies suggest that multidomain interventions may be more beneficial than cognitive training alone.

“What we don’t know is whether these lifestyle interventions affect disease processes such as slowing the accumulation of beta amyloid or tau tangles. It may be that clinicians will soon be able to recommend lifestyle changes (cognitive training, nutrition, exercise, etc.) along with medication treatments for the most robust dementia prevention,” Langbaum told Medscape Medical News.

In a statement from the nonprofit UK Science Media Centre, experts urged caution in interpreting the findings due to several limitations in the study and analysis.

Baptiste Leurent, PhD, associate professor of medical statistics at University College London in London, England, cautioned that the analysis relies on data from a trial conducted 25 years ago, which introduces “important” limitations.

“Only about 75% of the original participants were included, and additional sources of bias are likely, such as missing data and mortality. The analysis itself is also less rigorous and was not prespecified, which would normally be expected in a randomized trial,” Leurent commented.

He also noted that multiple subgroup analyses were conducted, and only one subgroup analysis produced a significant result, which is “generally regarded as strong enough evidence to demonstrate the intervention’s effectiveness. Further research is still needed to determine whether cognitive training can reduce the risk of dementia,” Leurent said.

Rachel Richardson, PhD, with The Cochrane Collaboration, said the ACTIVE study “appears to be a well-conducted [RCT], but one of its limitations is common to RCTs: The people recruited into the study aren’t necessarily representative of the whole population.”

“The study excluded people with various existing health conditions, including poor vision or hearing. More people were excluded from participating in the booster training sessions: To be eligible to participate, people had to have completed at least 8 out of the 10 initial training sessions. This again makes the sample less representative: for example, excluding people who fell ill during the first phase of the trial,” she said.

Richardson also noted that the other types of training in the ACTIVE study (memory plus booster training and reasoning plus booster training) also showed reductions in the risk for dementia, although these did not reach statistical significance.

This study was funded by National Institutes of Health grants from the National Institute on Aging. Albert, Langbaum, Leurent, and Richardson reported having no relevant disclosures.