LAUSR

Background Apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and mild cognitive impairment (MCI). Computer-based training programs can improve cognitive performance in elderly populations. However, the effects of computer-based interventions on MCI APOE ε4 carriers have never been studied before. Objective The effects of different web-based interventions and the APOE isoform-specific differences in training outcomes are investigated. Methods Using a quasi-experimental study design, 202 participants with MCI aged 60 years and older took part in three different intervention programs (physical and cognitive [Long-Lasting Memories, or LLM], cognitive [Active Control, or AC], or physical intervention [Physical Training Control, or PTC]) via an innovative information and communication technologies exergaming platform. Participants in each interventional group were subdivided into APOE ε4 carriers and non–APOE ε4 carriers. All participants underwent an extensive neuropsychological evaluation before and after the training, blood tests, and brain imaging. Results All interventions resulted in multiple statistically significant cognitive benefits after the intervention. Verbal learning (California Verbal Learning Test: immediate recall test score—LLM: P=.04; AC: P<.001), working memory (digit span forward and backward test scores—AC: P=.03; PTC: P=.02 and P=.006, respectively), and long-term memory (California Verbal Learning Test: delayed recall test score—LLM: P=.02; AC: P=.002; and PTC: P=.02) were improved. There was no statistically significant difference among the intervention effects. APOE ε4 presence moderates intervention effects as the LLM intervention improved only their task-switching processing speed (Trail Making Test, Part B: P=.03) and the PTC intervention improved only the working memory (digit span backward: P=.03). No significant performance alteration was noted for the APOE ε4+ cognitive AC training group. Conclusions None of the applied interventions could be identified as the optimal one; it is suggested, however, that combined cognitive and physical training and physical training via exergaming may be more effective for the high-risk MCI ΑPOE ε4+ subgroup.