Metabolic Syndrome Clinical Trial
Official title:
Exergaming Improves Executive Functions in Patients With Metabolic Syndrome
Background: Recent studies indicate that exercise-related games can improve executive
function, attention processing, and visuospatial skills.
Objective: This study investigates whether exercise with exergaming can improve the executive
function in patients with metabolic syndrome (MetS).
Methods: Twenty-two MetS patients were recruited and randomly assigned to the exergaming
group (EXG) and treadmill exercise group (TEG). The reaction time (RT) and
electrophysiological signal from the frontal (Fz), central (Cz), and parietal (Pz) cortex
were collected during a Stroop task after 12 weeks' exercise.
Introduction In recent years, the relationship between cognitive function and metabolic
syndrome has been widely studied. Metabolic syndrome (MetS) has been shown to be associated
with a decline in executive function due to multiple risk factors, including hypertension,
dyslipidemia, impaired glucose homeostasis, and abdominal obesity. Executive functions
include basic cognitive processes such as attentional control, cognitive inhibition,
inhibitory control, working memory, and cognitive flexibility.
Cognitive neuroscience is using Stroop tasks to measure selective attention capacity and
skills, as well as processing speed ability, indicating executive functions.
Electroencephalographic (EEG) activity using event-related positioning technology P300 and
N200 has been widely used to measure selective attention capacity and skills, and a
behavioral performance such as reaction time (RT) is commonly used to measure processing
speed ability. N200 negativity (200~350 ms post-stimulus) is an event-related potential
(ERP), which indicates attentional capacity that is usually induced before motion response
control and is related to the cognitive processes of stimulus recognition and
differentiation. P300 positivity (300~600 ms post-stimulus) is another ERP, reflecting
memory-related neural processing that is involved in categorizing incoming information and
updating the context of the working memory (e.g., encoding, rehearsal, recognition, and
retrieval).
It is well known that aerobic exercise training provides various beneficial clinical outcomes
in metabolic disease patients. Its effects on cognitive function, especially executive
function, also have been reported. Furthermore, recent studies reported that both aerobic and
resistance exercise training facilitate overall electrophysiological effects (e.g., increased
ERP P300 amplitudes) and behavior index (e.g., faster RT) in healthy elderly people. In
addition, aerobic exercise has also been reported to improve cognitive processes in cortical
cognitive control (P300 amplitude) in studies of chronic stroke patients.
Recently, exergaming (a combination of "exercise" and "gaming") has attracted much attention
as a novel exercise method to improve cognitive function because it utilizes video games that
require body movements while simultaneously presenting the user with a cognitively
challenging environment. Along with its popular usage for leisure and entertainment, there is
a growing interest in the application of exergaming to improve clinical outcomes. Recent
studies using exergaming showed beneficial effects on cognitive and dual-task functions,
which reduced falls in older adults as well as cardiovascular disease risks such as body fat,
serum adipokine levels, and lipid profiles. Exergaming also promoted executive functions and
cognitive processing speed in elderly and children. This growing evidence suggests that
exergaming's have the benefit of improving cognitive and physical functions.
Although many previous studies have reported improvements in cognitive function following
exergaming, it is not clear whether this benefit is due to an exercise effect or video game
effect. In addition, all of these studies measured RT, instead of ERP using EEG, which limits
to illuminate brain activities. Considering that EEG can measure electrical activities in
various cortex areas in the brain, it is necessary to investigate ERP using EEG to evaluate
executive function. Therefore, we examined the benefits of exergaming compared to normal
exercise and investigated executive function by measuring RT as well as N200 and P300 in
three cortex areas during Stroop tasks in patients with MetS.
Methods Participants A total of 22 MetS male and female patients aged between 50-80 years
participated in this study. MetS was defined according to the modified NCEP Adult Treatment
Panel III (NCEP-ATP III) definition for South Asians. Briefly, individuals with three or more
of the following criteria were defined as MetS: central obesity (waist circumference ≥90 cm
for men; ≥ 85 cm for women), fasting plasma glucose ≥100 mg/dL or current treatment for
diabetes mellitus, systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg or
current treatment for hypertension, serum triglyceride ≥150 mg/dL, low HDL cholesterol
(men<40 mg/dL; women<50 mg/dL). Subjects were asked to not exercise for 24 hours before the
experiment. They were also instructed to eat usual meals and to finish meals 4 hours before
the experiment, while avoiding alcohol 1 day before the experiment and caffeine during the 4
hours prior to the experiment. All subjects were required to complete a written informed
consent approved by the Institutional Review Board of Kosin University College of Medicine.
The sample size was calculated using sample size calculation software (G*Power version
3.1.9.2 for Windows; http://www.gpower.hhu.de), with effect size 0.484, statistical power
0.8, and statistical level of significance 0.05. This effect size was calculated from the
previous studies. As a result, the sample size for each group became 8, and we decided to
recruit 11 patients for each group, with a potential 30% dropout rate.
Exercise Training Interventions Exercise training was conducted at the Kosin University
Gospel Hospital U-healthcare Center. Each participant was instructed to immediately inform
the supervisor if he or she experienced any unusual symptoms during exercise training and to
consult a physician if needed. Subjects were excluded if they did not perform more than 80%
of the exercise sessions.
All subjects were randomly divided into two groups: exergaming and treadmill exercise group.
Subjects had 2 weeks of adaptation and then carried out 12 weeks of exercise training: 60
min/day, 60-80% of heart rate reserved (HRR), 3 days/week. Each exercise session consisted of
10 minutes of warm-up, 40 minutes of main exercise, and 10 minutes of warm-down.
The exergaming group (EXG) performed exercise using Exerheart® devices (D&J Humancare, Busan,
South Korea) composed of a running/jumping mat [730(W) × 730(D) × 130(H)] and a tablet PC on
a stand (can be adjusted to any height between 70 and 155 cm) (Supplemental Figure 1A).
Exerheart® is an exergaming developed for in-situ running along with the video game called
"Alchemist's Treasure" (D&J Humancare, Busan, South Korea). To play this game, the subject
has to run or jump on a spot on the mat to move a virtual avatar on the screen of the tablet
PC to the front, back, left, and right along with music (Supplemental Video 1 for online).
The subject can control the speed of avatar movement by running or jumping speed on the mat.
The treadmill exercise group (TEG) performed exercise using commercial treadmills (MOTUS,
Gyeonggi-do, South Korea). Each subject walked or ran on the treadmill at a comfortable
speed.
For both EXG and TEG, all subjects' heart rates (HR) during exercise were monitored using HR
monitors (polar RS400sd, Madison Height, Michigan, USA) to confirm that the value was within
the target HR range. The Karvonen formula (1957) was used to calculate HR reserve (HRR,
estimated maximal HR- resting HR) and target HR during exercise [(HRR × given percentage of
training intensity) + resting HR)].
Stroop Test For assessment of executive function, a computer-based version of the Stroop task
was administered with Telescan software (LAXTHA, Daejeon, South Korea). During the task,
subjects were presented with a color word appearing in the same color on congruent trials
(e.g. "blue" printed in blue) and in a different color on incongruent trials (e.g. "blue"
printed in green). To provide similar visual content, blue, green, and yellow were chosen as
stimuli.
Subjects performed Stroop task twice, pre- and post-exercise training. Subjects sat 1 meter
from the screen, and when the color words appeared on the screen, they clicked the left
keyboard for the congruent test and the right keyboard for the incongruent test. Subjects
were instructed to respond as quickly and accurately as possible. The rate of measurement
targeted for 50%. Each color word (vertical viewing angle: 2 °) was presented for 200 ms, and
the response was allowed within 1500 ms. The inter-stimulus interval varied randomly between
1500 and 2500 ms.
Electroencephalographic (EEG) Measurements EEG activity was recorded during the modified
Stroop task using a computerized polygraph system- Type A: A total of 31-channel Poly G-A
(LAXTHA, Daejeon, South Korea). Ag-AgCl electrodes (LAXTHA, Daejeon, South Korea) were placed
on frontal (Fz), central (Cz), and parietal (Pz) cortex areas, according to the International
10-20 system. Midline locations referenced to link earlobe electrodes. Horizontal and
vertical electrooculograms (EOGs) were monitored by electrodes placed above and below the
left eye and at the outer canthus of both eyes, respectively. The impedance of all electrodes
was maintained below 10 kΩ. The bandpass filter of the amplifier was 0.1-100 Hz, the sampling
rate was 1000 Hz, and a notch filter was at 60 Hz.
The N200 component was defined as the largest positive peak occurring between 200-350 ms
post-stimulus, and the P300 component was defined as the largest positive peak occurring
between 300~600 ms post-stimulus. N200 and P300 amplitudes were measured as the difference
between the mean pre-stimulus baseline and maximum peak amplitude. Telescan's built-in high
pass IIR filter was used for filtering. Waveforms were digitally smoothed with a low-pass
filter using a half-power cut-off of 10 Hz prior to analysis.
Statistical Analysis Due to the small sample size, we used nonparametric statistics for data
analysis. We used the Wilcoxon signed-rank test to examine the changes of each dependent
variable after intervention within each group. The Mann-Whitney U test was used to make
comparisons of the delta values between training groups (Δ‐EXG vs Δ‐TEG). The effect size of
partial eta-squared (η2) was reported for significant effects, where the alpha level for all
of the tests was set at 0.05. Data were expressed as mean ± standard deviation of mean. All
statistical tests were processed using the software SPSS 24 version.
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