Boston-based Akili Interactive Labs partnered with Pfizer to conduct a study of Akili's iOS-based game, Project Evo, in the hopes of using the game to detect indications of Alzheimer's in healthy individuals.

The month-long study of 100 participants includes a mix of some who have risk markers of potentially developing Alzheimer's and some who do not. All participants will take the game home and play it daily while researchers test whether the algorithms within the game can distinguish the group with risk markers.

"It is a large unmet need in Alzheimer's to be able to identify individuals who are at risk of developing Alzheimer's before major symptoms occur," Akili's VP of Research and Development Eddie Martucci told MobiHealthNews. "So currently, there is no very good simple cognitive means to do that. And so what we're doing in the study is looking to validate our game play with healthy individuals can actually distinguish those healthy individuals that have a high risk for potentially developing Alzheimer's."

How patients play the game

To play the game, a user navigates an alien, chosen specifically because it is culture neutral but also relatable, down a course by tilting a smartphone or tablet back and forth. While navigating the alien, the user must also respond to targets by tapping the screen. Martucci said the game uses touch screen and accelerometer mechanics. Because it is high resolution, the app keeps track of movements every 30 milliseconds and can therefore monitor the user's behavior and quickly adapt to the player.

"The user navigates this figure down a course and while they are navigating, the navigating becomes more difficult, and at the same time they are having to tap and react to objects which are coming at them," Martucci said. "It's built on an adaptive algorithm, so it gets faster, slower, harder, easier, depending on the user's progress, so it's personalized. Everyone who uses it gets a tailored and optimized cognitive experience."

The first video game-based screening tool?

Martucci sees the Pfizer trial as a potential test run for eventually deploying the app as a tool to find early cases of Alzheimer's.

"To our knowledge, the pharmaceutical industry has never used a video game to detect a disease and has also not done so in a setting of a real clinical tool and a real clinical trial," Martucci said. "We think this is a major step forward, certainly for us as a company, but broader in the digital health field. ...It's pretty exciting and almost unfathomable a couple years ago, when digital health was just getting started. As a field I think it's great. For us as a company, if this study goes well, then the potential for a video game that can be deployed remotely and cheaply in patient's homes that could help select individuals at risk for developing Alzheimer's would be huge for patients."

Akili Interactive labs was started by Boston-based PureTech Ventures and its first product was detailed in a Nature paper, which MobiHealthNews covered last September from the work of University of California San Francisco Associate Professor Adam Gazzaley. While that version was an academic prototype, Martucci and his team spent the last year and a half building an immersive video game from those mechanisms.

"Basically the main innovation from the Gazzaley Lab at UCSF is that one of the most fragile cognitive processes in the human brain is called interference processing," Martucci said. "And that's the ability to resist distractions or to multitask and so, what Adam Gazzaley did was build this game where you did two things at the same time...and basically how well you do at doing two things at the same time compared to when you do them in isolation ends up being a very fine measure of your cognitive ability."

Beyond Alzheimer's

Because the game targets what Martucci calls executive function, it could be deployed to more than just people with Alzheimer's. Eventually, Martucci plans to test the game over a range of populations such as people with ADHD and people with autism to see if the game can be tailored for different groups. On top of the Pfizer trial, Akili has finished another trial, is in the process of conducting two trials, and already plans to launch two this year.

The completed pilot studied around 40 children across the autism spectrum at University of California San Francisco and Akili plans to do another study later this year that also studies patients with autism.

Akili is already underway with a three-site study in pediatric ADHD, led by Duke University. This study is looking at the game as a potential therapeutic for ADHD and wants to see if patients improve performance on the game and improve cognition.

Another study, which started very recently, looks at ADHD and autism in a college-aged population in Vermont, which Martucci believes will be especially interesting because college students already play games regularly.

The two studies that Akili will be kicking off this quarter are for depression. One is a geriatric depression study, in a similar age range as the Alzheimer's study. The other is an NIH grant funded study of 150 people, which Martucci said is significant because the study is fully remote and administered completely through the patient's smartphone -- including the recruitment of individuals, screening, the full clinical trial intervention, follow-up and assessment.

"This is the first time this has ever been done -- a 150 person study with 50 in each arm," Martucci said. "For a first clinical study with a device, it's actually a pretty sizeable study. We'll get data on Evo, our game, as an intervention in depression, but we'll also get more community data on what are the most feasible recruitment methods, and how do people comply when this is administered totally remotely, how many times are they checking in, how many times are they looking for contact with a therapist, etc."

Using games to remove stigma

Akili Chief Business Officer Eric Elenko told MobiHealthNews that the study will provide those in the mental health field with a better understanding of how to use a remote approach well, which would be preferable for the patients who feel there is a stigma involved with mental health.

Akili also considered this factor when creating Evo.

"It was purposely built to look and feel like it could be on the shelf with other games that you would buy and download from the app store and we've built that on purpose," Martucci said. "That's a lot of the response we've gotten from kids and adults in the clinical studies -- that this feels and looks like a video game, and that's exactly what we want because with a platform like this we want people to engage in it just like an immersive entertaining game that they would pay for."

Moving forward, Akili plans to continue validating its product in concert with pharmaceutical companies so that it could potentially be a mainstream medical tool used to both identify and treat mental diseases. At some point, Martucci said, Akili plans to seek FDA approval.