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: Investigations of computerised cognitive training (CCT) show heterogeneous results in slowing age-related cognitive decline. Aims: To comprehensively evaluate the effectiveness of serious games-based CCT, integrating control conditions, neurophysiological and blood-based biomarkers, and subjective measures. Method: In this bi-centric randomised controlled trial with parallel groups, 160 participants (mean age 71.3 years) with cognitive impairment ranging from subjective decline to mild cognitive impairment, were pseudo-randomised to three arms: an intervention group receiving CCT immediately, an active control (watching documentaries) and a waitlist condition, which both started the CCT intervention after the control period. Both active arms entailed a 3-month intervention period comprising a total of 60 at-home sessions (five per week) and weekly on-site group meetings. In the intervention group, this was followed by additional 6 months of CCT, with monthly booster sessions to assess long-term training effects. Behavioural and subjective changes were assessed in 3-month intervals. Biological effects were measured by amyloid blood markers and magnetic resonance imaging obtained before and after training. Results: Adherence to the training protocol was consistently high across groups and time points (4.87 sessions per week). Domain-specific cognitive scores showed no significant interaction between groups and time points. Significant cognitive and subjective improvements were observed after long-term training. Voxel-based morphometry revealed no significant changes in grey matter volume following CCT, nor did amyloid levels moderate its effectiveness. Conclusions: Our study demonstrates no benefits of 3 months of CCT on cognitive or biological outcomes. However, positive effects were observed subjectively and after long-term CCT, warranting the inclusion of CCT in multicomponent interventions.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Dementia is projected to impact 152 million people by 2050, making it one of the most pressing global health challenges. The neurodegenerative process initiates well before clinical symptoms manifest, advancing from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and ultimately to dementia. Despite the growing prevalence, awareness of dementia prevention is limited, and many individuals express a desire to cease living upon diagnosis. Lifestyle interventions can mitigate cognitive decline, but there is a need for effective, scalable approaches to deliver these interventions to older adults. Digital health interventions, such as app-based just-in-time adaptive interventions (JITAIs), offer a promising solution, but their application in cognitively impaired older populations remains underexplored. Objective: This formative study evaluated the plausibility, acceptability, and adherence to a smartphone-based just-in-time adaptive digital lifestyle intervention delivered by a rule-based conversational agent (CA) among older adults with SCD or MCI. The primary focus was on adherence to the CA-initiated conversational turns (measured objectively via interaction logs), with secondary objectives including the perceptions of technology acceptance, the working alliance with the CA, self-reported adherence to the suggested health-promoting activity, and feedback for future improvements (through a questionnaire and short interview). Methods: This monocentric study investigated 15 participants (mean age = 70.3 years; 66.7% female and 33.3% male) with SCD (n=12) or MCI (n=3). Participants used the study app that delivered daily health-promoting activities through a CA over two weeks. Participants received notifications to engage in seven health-related activities, and adherence to the activity was self-reported. Post-intervention, participants rated their experience with the app and assessed their working alliance with the CA through the 6-item session alliance inventory. Data on smartphone usage, demographic information, and cognitive performance (via MoCA) were collected during a pre-intervention visit. Results: Participants rated the study app positively, especially regarding ease of use and a subset of the working alliance. Adherence to the CA-initiated conversational turn was measured at an average of 81.0% across 14 days. 27.1% of participants indicated as being vulnerable and 100% then responded with their state of receptivity, of which 82.7% were receptive to completing the activity, and 69.1% self-reporting adherence to the activity. There was no significant decline in adherence across the study period. Qualitative results support these findings and present two emerging themes: app enjoyment and enhancing engagement. Conclusions: This study demonstrates that smartphone-based JITAIs are feasible and generally well-accepted by older adults with SCD or MCI. However, the findings underscore the need for robust technological infrastructure and potential personal assistance to optimize adherence. Future interventions could benefit from integrating wearables to improve real-time engagement and accurately monitor adherence, ultimately supporting healthy aging and cognitive health in older populations.

Background: Cognitive training (CT) has been proposed to attenuate cognitive decline in early Alzheimer’s disease and can be administered remotely. Here, we describe the design and development of an adaptive app‐based CT to remotely train cognitive functions that are affected early in the course of Alzheimer’s disease. We furthermore present interim results of CT acceptance and adherence in a group of participants with subjective cognitive decline (SCD).Method: We used the Unity Game Engine software and the programming language C# to design a CT app with 16 games that target AD‐typical impairments in episodic and semantic memory and spatial processing, including working memory tasks to facilitate transfer processes (Figure 1). During each training session three games (each 10 min) are played. The training is adaptive to ensure a constant level of challenge, i.e., players progress to higher levels when they win rounds and decrease to lower levels when they lose rounds. The broad range of tasks ensures continued motivation and adherence of the participants over a prolonged training period. We aimed to design the game interfaces and navigation as user‐friendly as possible to maximize usability. Via an integrated help button participants can furthermore ask for help during home training. CT adherence can be assessed remotely.Result: Preliminary results on adherence and game experience show that participants with SCD (n = 62) like the games (5.49±0.13) and are motivated to perform well (6.3±0.08), despite being challenged (5.84±0.09) (7‐point Likert scale). After a 10‐week CT intervention, cognitive improvement is rated at 4.94±0.24 and participants would recommend the CT to a friend at 7.01±0.37 (9‐point Likert scale). Moreover, they would recommend that the games should be played for 32±2.64 min per day. The drop‐out rate is very low (4.6%). At the time of AAIC we will present additional data on acceptance/adherence and feasibility.Conclusion: Remotely administered app‐based CT is applicable in the home setting and successful in motivating participants with early AD, which is also reflected in high adherence rates and acceptability. Future research should extend app‐based interventions to also target individuals with advanced cognitive impairment and applications for use in care‐home settings.

BACKGROUND Dementia is projected to impact 152 million people by 2050, making it one of the most pressing global health challenges. The neurodegenerative process initiates well before clinical symptoms manifest, advancing from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and ultimately to dementia. Despite the growing prevalence, awareness of dementia prevention is limited, and many individuals express a desire to cease living upon diagnosis. Lifestyle interventions can mitigate cognitive decline, but there is a need for effective, scalable approaches to deliver these interventions to older adults. Digital health interventions, such as app-based just-in-time adaptive interventions (JITAIs), offer a promising solution, but their application in cognitively impaired older populations remains underexplored. OBJECTIVE This study evaluated the feasibility, acceptability, and adherence to a smartphone-based JITAI delivered by a rule-based conversational agent (CA) among older adults with SCD or MCI. The primary focus was on adherence to the CA-initiated conversational turns (measured objectively via interaction logs), with secondary objectives including the perceptions of technology acceptance, the working alliance with the CA, self-reported adherence to the suggested health-promoting activity, and feedback for future improvements (through a questionnaire and short interview). METHODS This monocentric study investigated 15 participants (mean age = 70.3 years; 66.7% female and 33.3% male) with SCD (n=12) or MCI (n=3). Participants used the study app that delivered daily health-promoting activities through a CA over two weeks. Participants received notifications to engage in seven health-related activities, and adherence to the activity was self-reported. Post-intervention, participants rated their experience with the app and assessed their working alliance with the CA through the 6-item session alliance inventory. Data on smartphone usage, demographic information, and cognitive performance (via MoCA) were collected during a pre-intervention visit. RESULTS Participants rated the study app positively, especially regarding ease of use and a subset of the working alliance. Adherence to the CA-initiated conversational turn was measured at an average of 80.95% across 14 days. 27.14% of participants indicated as being vulnerable and 100% then responded with their state of receptivity, of which 82.65% were receptive to completing the activity, and 69.13% self-reporting adherence to the activity. There was no significant decline in adherence across the study period. Qualitative results support these findings and present two emerging themes: app enjoyment and enhancing engagement. CONCLUSIONS This study demonstrates that smartphone-based JITAIs are feasible and generally well-accepted by older adults with SCD or MCI. However, the findings underscore the need for robust technological infrastructure and potential personal assistance to optimize adherence. Future interventions could benefit from integrating wearables to improve real-time engagement and accurately monitor adherence, ultimately supporting healthy aging and cognitive health in older populations.