Digital Cognitive Training in MCI and Early AD: Real World Evidence and Insights from a Large Online Cohort

Background The 21st Century Cures Act highlights the value of evidence obtained outside of traditional clinical trials (real world evidence, RWE) to enhance trial design and support health care decision making. Increasing use of computers and smartphones has accelerated the generation of RWE and enabled digital therapies including computerized cognitive training (CCT). CCT offers promise for improving cognitive outcomes in MCI and AD, but its effectiveness has not been fully established. Toward this end, we examined RWE on the effectiveness of CCT in MCI/AD using a large online dataset. Method We analyzed de‐identified data from a cohort of 82,984 individuals who participated in an online CCT program (Lumosity). Of these, 3514 reported a diagnosis of MCI or AD while the rest served as controls (N = 79,470). Participants completed the NeuroCognitive Performance Test (NCPT), a validated, computerized, online neuropsychological battery. A subset also completed a survey assessing real‐world cognitive functioning (RWC survey). Measures on both instruments were examined at baseline and after varying doses of CCT. Result At baseline, the MCI/AD cohort was significantly impaired on all eight NCPT cognitive subtests and the NCPT composite measure of global cognition compared to demographics‐matched controls (p<0.0001, N = 3514 MCI/AD, 79,470 healthy). The MCI/AD cohort was also impaired on the RWC survey (p<0.0001 for the composite score), particularly on items related to concentration or forgetfulness. Engagement with CCT varied among MCI/AD subjects with 2+ assessment timepoints (N = 1934), with an average of 340 CCT games played (SD = 482) over 112 days between assessments (SD = 104). The change from baseline in the NCPT composite measure increased with amount of CCT (p<0.0001, Cohen’s d = 0.31). RWC survey items also improved with training in a subset who completed them at multiple timepoints (p = 0.0530, N = 162). Conclusion This study provides RWE for the efficacy of CCT in MCI/AD on both objective and patient rated cognitive outcomes. The study also provides insights into dose effects. Such RWE will help optimize CCT interventions to improve cognitive symptoms of MCI and AD.