Relationship Between Within-Session Digital Motor Skill Acquisition and Alzheimer Disease Risk Factors Among the MindCrowd Cohort: Cross-Sectional Descriptive Study.

Background: Previous research has shown that in-lab motor skill acquisition (supervised by an experimenter) is sensitive to biomarkers of Alzheimer disease (AD). However, remote unsupervised screening of AD risk through a skill-based task via the web has the potential to sample a wider and more diverse pool of individuals at scale.

Objective: The purpose of this study was to examine a web-based motor skill game ("Super G") and its sensitivity to risk factors of AD (eg, age, sex, APOE ε4 carrier status, and verbal learning deficits).

Methods: Emails were sent to 662 previous MindCrowd participants who had agreed to be contacted for future research and have their APOE ε4 carrier status recorded and those who were at least 45 years of age or older. Participants who chose to participate were redirected to the Super G site where they completed the Super G task using their personal computer remotely and unsupervised. Once completed, different Super G variables were derived. Linear and logistic multivariable regression was used to examine the relationship between available AD risk factors (age, sex, APOE ε4 carrier status, and verbal learning) and distinct Super G performance metrics.

Results: Fifty-four participants (~8% response rate) from the MindCrowd web-based cohort (mean age of 62.39 years; 39 females; and 23 APOE ε4 carriers) completed 75 trials of Super G. Results show that Super G performance was significantly associated with each of the targeted risk factors. Specifically, slower Super G response time was associated with being an APOE ε4 carrier (odds ratio 0.12, 95% CI 0.02-0.44; P=.006), greater Super G time in target (TinT) was associated with being male (odds ratio 32.03, 95% CI 3.74-1192,61; P=.01), and lower Super G TinT was associated with greater age (β -3.97, 95% CI -6.64 to -1.30; P=.005). Furthermore, a sex-by-TinT interaction demonstrated a differential relationship between Super G TinT and verbal learning depending on sex (βmale:TinT 6.77, 95% CI 0.34-13.19; P=.04).

Conclusions: This experiment demonstrated that this web-based game, Super G, has the potential to be a skill-based digital biomarker for screening of AD risk on a large scale with relatively limited resources.