August 2016

We hope that you’re enjoying your summer. This is our second newsletter regarding the field of brain plasticity and cognitive training, and in this issue, I’m going to focus on the science and application of brain plasticity and cognitive training as they relate to dementia. As you may know, there has been some big news on this topic that has just become public.

By the way, you’re getting this email because you’re a scientific comrade—or you have collaborated with Posit Science. I thought you might be interested in an update on ‘what’s happening’ from our Posit Science research group’s perspective every so often, and we want to stay in touch with scientists pursuing these issues in a serious way.  If you don’t want to receive this email every other month or so, just email me and I’ll take you off the list. We can still be friends.





Now on to the…


The ACTIVE study shows that speed training (UFOV training) reduces the risk of dementia across ten years

As you know, the ACTIVE study is one of the largest randomized controlled trials of cognitive training to date. Organized and funded by the National Institutes of Health, ACTIVE enrolled 2,832 community-dwelling and generally healthy participants, with an average age of about 74. Volunteers were randomly assigned into one of three cognitive training groups (speed, memory, or reasoning training) and a fourth non-training control group. Subjects in the trained cohorts received a total of 10 hours of training in a) memory skills, b) reasoning skills, or c) computerized speed (useful field of view) exercises over 5 weeks. Memory and reasoning skills classes were designed to embed good skills into everyday life practices. Speed training was non-adaptive for the first 5 hours—then followed the kind of staircase adaptive progression you see on Posit Science’s version of this exercise (Double Decision on BrainHQ).

Approximately half of the people in each training group were randomly assigned to complete 4 hours of booster training at the end of the first and third years, to measure dose effects.

Again, speed (“UFOV”) training in particular will look familiar to researchers using BrainHQ because in 2007, Posit Science acquired the rights to this program and worked with Karlene Ball and Dan Roenker (its inventors) to build it in a more modern form as Double Decision on the BrainHQ platform.

In ACTIVE, comprehensive cognitive assessments were completed before training, after training, and +1, 2, 3, 5, and +10 year trial benchmarks. More than 50 peer-reviewed publications have reported these ACTIVE results to date.  To summarize, they confirm the a priori hypotheses that that all three cognitive training programs should show significant improvements in their proximal measures (e.g., speed training improved speed, but did not transfer to reasoning), and that all three programs would drive significant generalization, protecting against the expected decline in instrumental activities of daily living. In addition, speed training uniquely showed further generalization power, showing improvements in the booster group in directly observed functional measures, protection against declines in health-related quality of life and depressive symptoms, and a reduction in at-fault car crashes.

The new analysis, presented by Jerri Edwards (University of South Florida) at the Alzheimer’s Association International Conference on Monday finally got around to examining the effects on the 10-year incidence of dementia, using previously established interview-based and performance-based criteria characterizing cognitive and functional status. Survival curve analysis of the intent-to-treat population showed that the group randomized to speed training was significantly less likely than the control to develop dementia (HR=0.67, 95% CI 0.49-0.91, p=0.012). Analyses examining dose and adjusting for sample characteristics associated with dementia showed a significant effect of training dose (HR=0.92 per session delivered, 95% CI=0.87-0.98, p=0.013).

In the control population, the incidence of dementia was 14%. In the group performing 10 or fewer hours of speed training the incidence was 12.1%, while in the group performing 11+ hours of speed training, dementia incidence was 8.2%. Adjusting for various differences, the speed training booster group showed a 48% risk reduction compared to controls.

These are not unexpected, but at the same time exciting results because ACTIVE is the first randomized controlled trial of anything—brain training, physical exercise, nutritional supplement/diet, or pharmaceutical—to show that in healthy adults it IS possible to reduce the risk of going on to dementia.

It is also exciting because we know so much more about how to strengthen brains by augmenting what is delivered via speed training (Double Decision), and because it is a virtual certainty that we can keep more people safer, longer with adjusted dosing.

A Human Brain Imaging Study Sheds Light on Mechanism

A recently published study from Dr. Vankee Lin (University of Rochester) has revealed a little more about what is happening when people do speed training. She randomized 21 people with amnestic mild cognitive impairment into two groups: speed training (using 5 exercises now in BrainHQ, including Double Decision) vs an online computer-games control group. Using fMRI functional connectivity analysis, she showed that speed training stops decline in default mode network connectivity, and drives renormalizing changes in central executive network connectivity.

How Could this Work?

Many people might ask how such a short brain-training intervention have such significant and long-lasting effects. Maybe it was obvious. After all, at the behavioral level, ACTIVE had already shown that speed training improved speed and functional performance, and protected against decline in health-related quality of life and depressive symptoms. Other studies have shown that trained individuals are not just safer, but also more confident and active drivers. Improved real-world cognitive performance, sustained everyday action out in the world, and decreased functional decline is pretty much the definition of dementia risk reduction. And processing speed is, after all, a signature indicator of aging and brain health.

But importantly, we also know that limited training in this form can have a great impact on other related contributors to brain health status—like myelination, physical status and functional processes controlling coordinated neurological processing, processes supporting higher-speed actions, and processes contributing to neurological protection.


Of the hundreds of studies using computer-delivered brain-training programs that are now underway, we’d like to feature exemplary ongoing studies of potentially broad interest and societal value in each of our quarterly reports. Let me know about YOUR projects so that we can tell everyone in our research family about your work in future newsletters.

New cognitive training trial in healthy older adults exploring mechanisms of training and default mode network activity

In a study supported by the National Institute on Aging, Dr. Hyunkyu Lee of Posit Science and Drs. Michelle Voss and Frederic Wolinsky at the University of Iowa are collaborating to define the joint behavioral and neurological impacts of computerized training in healthy older adults ( NCT02331784). As shown in prior work, the pathological processes that lead to Alzheimer’s disease (AD) begin years before its diagnosis. Neuroimaging studies have shown that the signature markers of AD initially arise within the “default mode network” (DMN) in the brain—cortical zones that are progressively disconnected in healthy aging. As an increasingly disconnected, inactive DMN is slowly undergoing plastic simplification, the current trial employs a largely speed-based BrainHQ training approach to increase resilience and restore default system integrity, as compared to an active computer-games control condition. The goal of the trial is to jointly measure cognitive and neurological effects of training in 55 healthy older adults (by recording changes in cognitive function and in implicit and explicit DMN-level neurological abilities) and document changes in resting-state neural connectivity of the DMN via fMRI.

The trial should be completed late spring 2017. Dr. Lee’s team hopes to use outcomes from this trial and a potential subsequent phase II trial to optimize dosing to assure protective benefits, and to further define the protective neurological changes that contribute to the cognitive function improvements and reduced risk for dementia seen in previous studies.


The Institute of Medicine is Thinking About Primary Prevention

Finally, in related news, the Institute of Medicine (now called the National Academy of Medicine), is beginning an evidence-based review on primary prevention factors and interventions that could decrease the risk of developing dementia, mild cognitive impairment, and age-related cognitive impairment. This effort follows on from last year’s review of cognitive aging, which included a very brief review of cognitive training and the statement of five specific criteria by which cognitive training programs should be evaluated for efficacy. Their goal with the new study is to make recommendations to inform public health strategies.

We think that given the above-described results, this is exactly the right time for this review. We agree with the Alzheimer’s Association, who concluded in their 2015 review of modifiable risk factors for cognitive decline and dementia that “the evidence has now reached a point that it can no longer remain simply an exercise in academic discussion.”

A shared publication database

The scientific literature in our field is scattered across many journals. We try to keep up with it, and am committed to making our efforts public. We ask you to help us keep up with this fast-moving feast!  You can see our shared database of published randomized controlled trials in brain training online. It’s worth taking a look, as you might find something you weren’t aware of before that can be helpful for you.  As always, please email us any papers that you know about that you find to be missing from this compendium.