BACKGROUND:
Simultaneous motor-cognitive training interventions are considered promising to prevent
the decline in cognitive functioning in older adults with mild neurocognitive disorder
(mNCD) and can be highly motivating when applied in form of exergames. To ameliorate the
effectiveness of exergaming, the neurobiological mechanisms as well as the most effective
components for exergame interventions remain to be established. Besides establishing the
most effective components [i.e., qualitative (e.g., type and content of training) and
quantitative (e.g., frequency, intensity/complexity, session duration, intervention dose
and adaptation over time) exercise and training variables] of exergames for cognition, it
is crucial to also account for the users' perspective when designing and developing novel
exergames or training concepts.
On this basis, a novel exergame-based training concept (called the 'Brain-IT'
exergame-based training concept) was developed specifically for older adults with mNCD
with the aim to halt and/or reduce cognitive decline and improve quality of life in older
adults with mNCD. This exergame-based training concept has been developed on basis of a
structured, iterative, and evidence-based approach based on a theoretical framework - The
'Multidisciplinary Iterative Design of Exergames (MIDE): A Framework for Supporting the
Design, Development, and Evaluation of Exergames for Health'. The 'Brain-IT'
exergame-based training concept represents a guideline for applying exergame-based
motor-cognitive training by standardizing the training characteristics (e.g. training
frequency, duration), as well as the structure and content of the training, whereas the
exergame device and the games used within each of the defined neurocognitive domains can
be replaced at will by alternative exergames. In this study, our training concept is
implemented using the 'Senso (Flex)' (Dividat AG, Schindellegi, Switzerland), because
this training device is already widely used for motor-cognitive training within geriatric
populations, physiotherapies or in rehabilitation in Switzerland and was found to be
suitable to implement our training concept. A step-by-step explanation of our
methodological approach including the basis for the decision for the design of the
exergame-based training concept as well as the complete 'Brain-IT' exergame-based
training concept with sufficient details to allow full replication has been published as
a methodological paper (doi: 10.3389/fnagi.2021.734012). The 'Brain-IT' exergame-based
training concept has already been tested in a pilot randomized controlled trial and has
shown good results in feasibility (i.e. recruitment, adherence, compliance, attrition),
usability (i.e. system usability), and acceptance (i.e. enjoyment, training motivation
and perceived usefulness) (unpublished work; NCT04996654). Based on the findings of this
study, some minor modifications were incorporated to optimize the training concept so
that it can be applied in a larger sample of patients to be evaluated on its
effectiveness to halt and/or reduce cognitive decline and improve quality of life in
older adults with mNCD.
OBJECTIVES & HYPOTHESES:
This study explores the effectiveness of the 'Brain-IT' training to improve global
cognitive func-tioning in older adults with mNCD. With this, we aim to get a sufficiently
precise estimate of the treatment effect to minimize the sample needed for a future
full-scale RCT.
Null Hypothesis (H0): In older adults with mNCD, the addition of the 'Brain-IT' training
to usual care has no significant effect on global cognitive functioning compared to usual
care.
Alternative Hypothesis (HA): In older adults with mNCD, the addition of the 'Brain-IT'
training to usual care results in differing effects on global cognitive functioning
compared to usual care.
As secondary objectives, the effects of the 'Brain-IT' training on: (1) domain-specific
cognitive functioning (i.e. learning and memory, complex attention, executive function,
and visuospatial skills), (2) brain structure and function, (3) spatiotemporal parameters
of gait, (4) IADL and (5) psychosocial factors (i.e. QoL, and levels of depression,
anxiety, stress), and (6) cardiac vagal modulation (i.e. resting vagally-mediated heart
rate variability (vm-HRV)) in older adults with mNCD as compared to usual care will be
explored. Brain structure and function will be evaluated to explore possible underlying
neural changes of the training in relation to adaptations in cognitive performance. For
the remaining outcomes, the following hypotheses were formulated:
Null Hypothesis (H0): In older adults with mNCD, the addition of the 'Brain-IT' training
to usual care has no significant effect on (1) domain-specific cognitive functioning, (3)
spatiotemporal parameters of gait, (4) IADL and (5) psychosocial factors (i.e. QoL, and
levels of depression, anxiety, stress), and (6) cardiac vagal modulation (resting vm-HRV)
com-pared to usual care.
Alternative Hypothesis (HA): In older adults with mNCD, the addition the 'Brain-IT'
training to usual care results in differing effects on (1) domain-specific cogni-tive
functioning, (3) spatiotemporal parameters of gait, (4) IADL, (5) psychosocial factors
(i.e. QoL, and levels of depression, anxiety, stress), and (6) cardiac vagal modulation
(resting vm-HRV) com-pared to usual care.
METHODS:
A two-arm, parallel-group, single-blinded (i.e. outcome evaluator of pre- and
post-measurements blinded to group allocation) randomized controlled trial with an
allocation ration of 1 : 1 (i.e. intervention : control) including 34 - 40 older adults
with mNCD will be conducted between May 2022 and December 2023.
After recruitment, interested subjects will be screened on eligibility between May 2022
and September 2023. 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 investigators, who will also be
available to answer open questions and clarify uncertain-ties of participants. It will
further be verified, that withdrawal is permitted at any time during the study without
having to give a reason. After sufficient time for considerations (i.e. at least 24 h
after handing out the study information sheet, but on average around two weeks), suitable
patients willing to take part in the study will provide written informed consent in a
second in-person meeting with the study team at the interested persons' home or at one of
the study centres, depending on their preferences. If eligible patients decline to
participate in the study, all data researched by their doctors or therapists and
submitted to the study team will be permanently deleted. After providing written informed
consent, the participants will be fully screened on eligibility, and the third study
appointment (pre-measurements) will be scheduled. For participants recruited in the area
of Zurich, the pre-measurements will take place at ETH Hönggerberg (Robert-Gnehm-Platz 1,
CH-8093 Zurich). For participants recruited in the area of St.Gallen, the
pre-measurements will take place at Eastern Switzerland University of Applied Sciences
(Vadianstrasse 29, CH-9000 St.Gallen). The measurements will take approximately 60 - 90
min. For all participants who have no contraindications to MRI, an additional appointment
to conduct the MRI scan will be scheduled. The MRI scan will take place at University
Hospital Zurich (Rämistrasse 100, CH-8006 Zurich) and will take approximately one hour
(including preparation). After completing the pre-measurements, participants will be
randomly allocated to the intervention group (i.e. 'exergame group') or control group
(i.e. 'usual care'). All participants will be instructed about their respective
intervention procedures. For participants in the exergame group, the device will be
installed at their homes, they will get a safety instruction and will be familiarized
with the exergame training system 'Senso Flex', and the study intervention will be
started according to the newly developed 'Brain-IT' exergame-based training concept (see
section 'Intervention'). After completing the twelve-week intervention period,
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. No compensation will be granted to the participants, but
detailed feedback on individual performance as well as the study outcomes in general will
be provided at the end of the trial if desired.