Video Game May Help Identify Preclinical Alzheimer's

Michael Vlessides

May 09, 2019

Spatial navigation ability, as measured by a virtual reality computer game, can help distinguish individuals who are at high genetic risk of developing Alzheimer's disease (AD) from those who are not.

Using the Sea Hero Quest navigation game, a team of French and British researchers compared the results of 69 participants (ages 50-75 years) with a benchmark population of 27,108 others who had previously played the game.

They concluded that a person's game results can be correlated with genetic risk of developing AD, and can also serve as a discriminator between individuals who exhibit signs of healthy aging and those at high risk of AD. 

"The trial's primary finding is that we can detect early cognitive changes for Alzheimer's disease long before people actually begin to suffer memory problems," lead author Michael Hornberger, PhD, professor of applied dementia research at the Norwich Medical School, United Kingdom, told Medscape Medical News.

"And for the first time, it gives us a cognitive measure that really looks at these at-risk people. The other important finding from this study is that we can, for the first time, look at individuals with a little more of a personalized approach for diagnosis," he added.

The study was published online April 23 in the National Academy of Sciences' journal PNAS.

Subtle Navigation Changes

Spatial navigation has recently begun to emerge as a critical factor in identifying preclinical AD. Indeed, several of the brain areas affected by preclinical AD pathophysiology are key components in the spatial navigation network.

Recent evidence suggests abnormal spatial navigation patterns may become evident even before signs of episodic memory deficits, which are considered to be the current gold standard AD diagnosis.

However, despite the emergence of such data, inter-individual differences in navigation ability — along with the interplay of such demographic risk factors as apolipoprotein E (APOE), age, and sex on spatial navigation — can make it challenging to identify individuals who are at high risk of AD in preclinical stages.

"We know in Alzheimer's disease that very subtle navigation changes can occur before people develop memory problems," said Hornberger. "But the issue was that to be able to detect these subtle changes, we needed to get large data to compare people against.

"With that in mind we launched Sea Hero Quest in 2016. It was a huge success and we collected data from more than 4.5 million people worldwide. The current study takes our research to the next step where we wanted to see if we can use our dataset to identify people at risk of developing Alzheimer's disease," he added.

To help bridge this knowledge gap, the investigators recruited 150 patients between 50 and 75 years of age for the APOE genotyped cohort between February 2017 and June 2017. Of those, 69 underwent cognitive testing.

They then generated a population-level benchmark dataset by extracting a subset from the global Sea Hero Quest database that matched the demographic profile of the genotype cohort: British players ages 50-75 years. Following extraction, 14,470 British men and 12,710 British women (n = 27,180) were used as the normative sample of heathy navigation performance.

In doing so, the researchers examined the relationship between three Sea Hero Quest outcome variables: wayfinding distance traveled, wayfinding duration, and flare accuracy. Of these, they considered wayfinding as the primary outcome measure, "as early Alzheimer's disease is characterized by abnormal changes in the grid cell code of the entorhinal cortex," they write.

Potential Therapeutic Window

Investigators found that high-risk preclinical cases of AD were reliably distinguished from low-risk participants using spatial navigation benchmarks generated by the database. Most tellingly, the study showed a main effect of genotype (b = 0.22; P = .004) on wayfinding distance, a finding the researchers said replicates previous findings in APOE ε4 carriers.

Specifically, the analysis showed adults at genetic risk of AD navigated further during wayfinding and also showed a bias in navigating toward the border of the virtual environment in large, open areas.

This, they note, "supports the hypothesis that suboptimal navigation performance is present in preclinical Alzheimer's disease" and this is detectable on levels of the game.

The investigators also found that while baseline navigation ability differed between men and women, sex did not interact with the APOE genotype to influence the manifestation of AD-related spatial disturbance.

Interestingly, such differences were indistinguishable using neuropsychological episodic memory tests.

These results suggest that normative benchmark data from the Sea Hero Quest game may be used to classify spatial impairments in healthy participants at risk of developing AD. As such, the test provides a potential stepping stone for individualized diagnostics and outcome measures of cognitive symptoms in preclinical AD.

"This could have major implications, and we're aware that it also carries a large responsibility," said Hornberger. Because for many people, the next question is 'What do I do if I know I am developing the first signs of dementia?'

"On the plus side, we know that Alzheimer's disease can develop a long time after we have these memory changes. This gives us a very large therapeutic window, which may allow high-risk patients to potentially change the trajectory of disease and either delay or alleviate disease onset," he added.

Good Test, Not a Great Test

Commenting on the findings for Medscape Medical News, Morris Moscovitch, PhD, professor of psychology, University of Toronto, Canada, said while Sea Hero Quest boasts many strengths, the test is not ready to stand on its own.

"It's a decent test; I don't think it's a great test," he said. "The specificity isn't perfect. It's not as though a person is in the clear if they perform well on the test. On the other hand, if a person does poorly on it, then it's probably a mark of something."

Nevertheless, Moscovitch was quick to note that one of the major strengths of the game is its massive database.

"The best thing about this test is that it was given to such a large cohort. So you have good norms, and you can tell if a person falls off those norms. But I don't think it can be used as a marker on its own," he said.

Hornberger and Moscovitch have disclosed no relevant financial relationships.

PNAS. Published online April 23, 2019. Abstract

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