After recruitment, interested subjects will be screened on eligibility between July and September 2021. All potential subjects will be fully informed about the study procedures by providing verbal explanations and an information sheet. Expected effects, benefits and risks of the study will be explained by the investigator, who will also be available to answer open questions and clarify uncertainties of participants. It will further be verified, that withdrawal is permitted at any time during the study without giving any reason. After sufficient time for considerations, suitable patients willing to take part in the study will provide written informed consent prior to any measurements and the first study appointment will be scheduled. At the first scheduled appointment, pre-measurements (PRE) will be performed. Thereafter, participants will be randomly allocated to the intervention group (i.e. 'exergame group') or active control group (i.e. 'usual care'). Subsequently, participants in the exergame group will be familiarized with the exergame training system 'Dividat Senso' (Dividat AG, Schindellegi, Switzerland; CE certification), and the study intervention will be started according to the newly developed exergame-based intervention concept. After completing the twelve-week training intervention, post-measurements (POST) will be performed for both groups. Both, the pre- and the post-measurements will take place and within two weeks prior to starting or after completing the intervention.

INTERVENTIONS:

Usual Care:

An active control group will proceed with usual care as provided by the memory clinics where the patients are recruited.

Exergame Group:

Participants will perform a twelve-week training intervention in addition to their usual care as provided by the memory clinics where the patients are recruited. The training intervention will be prescribed according to a newly developed exergame-based intervention concept. The training intervention concept was planned and reported using the Consensus on Exercise Reporting Template (CERT): It consists of an individually adapted multi-domain exergame-based simultaneous cognitive-motor training with incorporated cognitive tasks that will be adopted with a deficit-oriented focus on the neurocognitive domains of (1) learning and memory, (2) executive function, (3) complex attention, and (4) perceptual-motor function. According to the training concept, each participant is instructed to train 5x/week for 21 min per session resulting in a weekly exercise volume of 105 min. All training sessions are planned to take place at participant's homes using the exergame training system Dividat Senso (Dividat AG, Schindellegi, Switzerland; CE certification). In case the training cannot be performed at home, the training sessions will be performed at ETH Hönggerberg and the instructed training frequency is reduced to 3x/week for 21 min per session resulting in a weekly volume of 63 min. Nonetheless, it is still recommended to train at the suggested optimal frequency (5x/week) and volume (105 min/week).

The training concepts is structured in three phases. It starts with a familiarization period of two weeks. During this phase, most of the training sessions (i.e. 4 out of 5 sessions) are supervised. After this initial guided familiarization period, supervision of training sessions is gradually reduced to 1x/week during a four-week transition phase. This transition phase aims to lead participants to being able to train independently. In this transition phase, the amount of supervision of training sessions is individually determined within a predefined range in accordance with the capabilities and preferences of the participants. From the 7th week until completion of the training intervention, semi-autonomous training with one supervised training session per week are prescribed for each participant.

Throughout the training intervention period, all sessions will be prescribed following the same basic structure: Each session consists of three blocks with 3 phases per block. Phase 1 - Facilitation aims to apply a moderate physical intensity in the context of challenging but feasible cognitive and motoric demands mainly intending to trigger neurophysiological mechanisms, which promote neuroplasticity while additionally using cognitive stimulation to guide these neuroplastic processes. This phase includes games focusing on neurocognitive domains that are least impaired. The external task demand is individually adapted to ensure an appropriate internal training load. More specifically, the internal training load is subdivided into a fixed component (i.e. physical intensity) and a variable component (i.e. neurocognitive (game-) demand). An additional stepping task is used to set the level of physical intensity. It includes walking on the spot at a predefined stepping frequency that is needed to reach a moderate level of physical intensity (i.e. ranging between 40 and 59 % heart rate reserve (HRR))). The stepping frequency will be individually determined for each participant. A battery figure add-on is visible in the center of the screen that provides real-time visual feedback whether the predefined stepping frequency is reached. More specifically, if the predefined minimal required stepping frequency is reached or exceeded, the battery stays at equilibrium or fills. As long as the battery level is above 80 % (indicated by a line), the battery stays green. If the participants' stepping frequency falls below the predefined minimal required stepping frequency, the battery level decreases, and the battery turns orange (40 - 80 %) or red (below 40 %) indicating that the stepping frequency should be increased. On top of this fixed physical intensity, a variable amount of neurocognitive (game-) demands (e.g. game type, task complexity, predictability of required tasks) is applied. Since the physical intensity is kept constant, changes in the overall internal training load can mainly be attributed to these neurocognitive and motoric (game-) demands and, accordingly, the internal training load can be adjusted on basis of these game characteristics. Therefore, the neurocognitive demands of the exergame are individually adapted in order to ensure an appropriate total internal training load. The monitoring and adaption of the internal training load will be based on predefined progression rules for adapting characteristics of external training load. Phase 2 - Guidance aims to make use of the triggered neurophysiological mechanisms from phase 1 to specifically guide neuroplastic processes of the mainly impaired neurocognitive domain. Therefore, games focusing on the mainly impaired neurocognitive domain for the individual participant (e.g. amnestic single domain =\> learning and memory) are used. These games solely focus on cognitive and motoric demands, but not on physical exercise intensity. The cognitive-motoric demands of the exergame (also called 'external load') are individually adapted in order to ensure an appropriate internal training load. The monitoring and adaption of the internal training load will be based on predefined progression rules for adapting characteristics of external training load. Phase 3 - Coherence aims to implement a structured approach as a surrogate for the breaks between games. More specifically, resonance breathing training guided by heart rate variability biofeedback (HRVB) is used. HRVB training is a behavioral intervention aiming to increase cardiac autonomic control, to enhance homeostatic regulation, and to regulate emotional state. It includes paced breathing for two minutes following the rhythm of the individually predetermined resonance frequency visualized on the screen of the exergame device. The resonance frequency will be evaluated for each participant before starting the training intervention.