Background Alzheimer’s disease (AD) is a major public health issue. Cognitive interventions such as computerized cognitive trainings (CCT) are effective in attenuating cognitive decline in AD. However, in those at risk of dementia related to AD, results are heterogeneous. Efficacy and feasibility of CCT needs to be explored in depth. Moreover, underlying mechanisms of CCT effects on the three cognitive domains typically affected by AD (episodic memory, semantic memory and spatial abilities) remain poorly understood. Methods In this bi-centric, randomized controlled trial (RCT) with parallel groups, participants (planned N = 162, aged 60–85 years) at risk for AD and with at least subjective cognitive decline will be randomized to one of three groups. We will compare serious game-based CCT against a passive wait list control condition and an active control condition (watching documentaries). Training will consist of daily at-home sessions for 10 weeks (50 sessions) and weekly on-site group meetings. Subsequently, the CCT group will continue at-home training for an additional twenty-weeks including monthly on-site booster sessions. Investigators conducting the cognitive assessments will be blinded. Group leaders will be aware of participants’ group allocations. Primarily, we will evaluate change using a compound value derived from the comprehensive cognitive assessment for each of three cognitive domains. Secondary, longitudinal functional and structural magnetic resonance imaging (MRI) and evaluation of blood-based biomarkers will serve to investigate neuronal underpinnings of expected training benefits. Discussion The present study will address several shortcomings of previous CCT studies. This entails a comparison of serious game-based CCT with both a passive and an active control condition while including social elements crucial for training success and adherence, the combination of at-home and on-site training, inclusion of booster sessions and assessment of physiological markers. Study outcomes will provide information on feasibility and efficacy of serious game-based CCT in older adults at risk for AD and will potentially generalize to treatment guidelines. Moreover, we set out to investigate physiological underpinnings of CCT induced neuronal changes to form the grounds for future individually tailored interventions and neuro-biologically informed trainings. Trial registration This RCT was registered 1st of July 2020 at clinicaltrials.gov (Identifier NCT04452864).

Background Recent studies suggest that computerized puzzle games are enjoyable, easy to play, and engage attentional, visuospatial, and executive functions. They may help mediate impairments seen in cognitive decline in addition to being an assessment tool. Eye tracking provides a quantitative and qualitative analysis of gaze, which is highly useful in understanding visual search behavior. Objective The goal of the research was to test the feasibility of eye tracking during a puzzle game and develop adjunct markers for cognitive performance using eye-tracking metrics. Methods A desktop version of the Match-3 puzzle game with 15 difficulty levels was developed using Unity 3D (Unity Technologies). The goal of the Match-3 puzzle was to find configurations (target patterns) that could be turned into a row of 3 identical game objects (tiles) by swapping 2 adjacent tiles. Difficulty levels were created by manipulating the puzzle board size (all combinations of width and height from 4 to 8) and the number of unique tiles on the puzzle board (from 4 to 8). Each level consisted of 4 boards (ie, target patterns to match) with one target pattern each. In this study, the desktop version was presented on a laptop computer setup with eye tracking. Healthy older subjects were recruited to play a full set of 15 puzzle levels. A paper-pencil–based assessment battery was administered prior to the Match-3 game. The gaze behavior of all participants was recorded during the game. Correlation analyses were performed on eye-tracking data correcting for age to examine if gaze behavior pertains to target patterns and distractor patterns and changes with puzzle board size (set size). Additionally, correlations between cognitive performance and eye movement metrics were calculated. Results A total of 13 healthy older subjects (mean age 70.67 [SD 4.75] years; range 63 to 80 years) participated in this study. In total, 3 training and 12 test levels were played by the participants. Eye tracking recorded 672 fixations in total, 525 fixations on distractor patterns and 99 fixations on target patterns. Significant correlations were found between executive functions (Trail Making Test B) and number of fixations on distractor patterns (P=.01) and average fixations (P=.005). Conclusions Overall, this study shows that eye tracking in puzzle games can act as a supplemental source of data for cognitive performance. The relationship between a paper-pencil test for executive functions and fixations confirms that both are related to the same cognitive processes. Therefore, eye movement metrics might be used as an adjunct marker for cognitive abilities like executive functions. However, further research is needed to evaluate the potential of the various eye movement metrics in combination with puzzle games as visual search and attentional marker.

BACKGROUND Recent studies suggest that computerized puzzle games are enjoyable, easy to play, and engage attentional, visuospatial, and executive functions. They may help mediate impairments seen in cognitive decline in addition to being an assessment tool. Eye tracking provides a quantitative and qualitative analysis of gaze, which is highly useful in understanding visual search behavior. OBJECTIVE The goal of the research was to test the feasibility of eye tracking during a puzzle game and develop adjunct markers for cognitive performance using eye-tracking metrics. METHODS A desktop version of the Match-3 puzzle game with 15 difficulty levels was developed using Unity 3D (Unity Technologies). The goal of the Match-3 puzzle was to find configurations (target patterns) that could be turned into a row of 3 identical game objects (tiles) by swapping 2 adjacent tiles. Difficulty levels were created by manipulating the puzzle board size (all combinations of width and height from 4 to 8) and the number of unique tiles on the puzzle board (from 4 to 8). Each level consisted of 4 boards (ie, target patterns to match) with one target pattern each. In this study, the desktop version was presented on a laptop computer setup with eye tracking. Healthy older subjects were recruited to play a full set of 15 puzzle levels. A paper-pencil–based assessment battery was administered prior to the Match-3 game. The gaze behavior of all participants was recorded during the game. Correlation analyses were performed on eye-tracking data correcting for age to examine if gaze behavior pertains to target patterns and distractor patterns and changes with puzzle board size (set size). Additionally, correlations between cognitive performance and eye movement metrics were calculated. RESULTS A total of 13 healthy older subjects (mean age 70.67 [SD 4.75] years; range 63 to 80 years) participated in this study. In total, 3 training and 12 test levels were played by the participants. Eye tracking recorded 672 fixations in total, 525 fixations on distractor patterns and 99 fixations on target patterns. Significant correlations were found between executive functions (Trail Making Test B) and number of fixations on distractor patterns (<i>P</i>=.01) and average fixations (<i>P</i>=.005). CONCLUSIONS Overall, this study shows that eye tracking in puzzle games can act as a supplemental source of data for cognitive performance. The relationship between a paper-pencil test for executive functions and fixations confirms that both are related to the same cognitive processes. Therefore, eye movement metrics might be used as an adjunct marker for cognitive abilities like executive functions. However, further research is needed to evaluate the potential of the various eye movement metrics in combination with puzzle games as visual search and attentional marker.