healthmedicinet

Subjects

Participants were recruited from community dwellers in Sumiyoshi-ku, Osaka City, Japan
by advertising in a local magazine. The inclusion criteria were healthy, sedentary
elderly people, aged over 65 years with no habit of regular exercise for more than
1 h per week. Subjects who had a history of ischemic heart disease, chronic heart
failure, severe hypertension, diabetes, marked dementia with a score of under 60 for
the Modified Mini-Mental State (3MS) examination, or a neuropsychiatric disorder were
excluded from the study. All of these concerns were assessed using an interview sheet.
The subjects who were judged by a physician to be unable or ill-equipped to participate
in the exercise program were also excluded. Written informed consent was obtained
from all participants, and the study protocol was approved by the ethics committee
of Osaka City University Graduate School of Medicine.

Study design

The present study was a 12-week randomized, controlled trial. It was designed as a
single-blinded study, that is, the outcome assessors and the exercise instructor,
but no participant knew the group identity. All applicants visited our research center
in Osaka City University, and underwent baseline measurements, including the 3MS examination,
an evaluation for motor ability, and laboratory analysis. The participants who met
the inclusion criteria were randomly assigned to the dual-task training (DT) or the
single-task training (ST) group. A disinterested third person performed the randomization
by computer processing with the random number generation program. In brief, the person
gave the different random number to each participant on the computer software, and
ranked them due to the random number. The participants who had the ranking of even
number were assigned to the DT group, and odd number to the ST group. The above operation
was repeated until the person achieved balance on gender, age, years of education,
and the total scores of 3MS exam. Subsequently, the subjects in each group engaged
in the 12-week exercise program provided at Sumiyoshi Sports Center, a gymnasium located
in Osaka City. After the intervention, all the clinical parameters were re-examined.

Exercise intervention

All participants in the DT and the ST groups received 1-hour exercise training separately
(in separate rooms for each group), three times a week, for 12 weeks. All sessions
were supervised by a trained instructor.

A training session comprised 15 min of mental gymnastics mainly made up of complicated
motion of the fingers, 25 min of resistance training, 10 min of aerobic exercise,
and finally 10 min of systemic flexibility exercise composed by 8?10 poses. Resistance
training gradually progressed from exercises like knee extensions or thigh-raises
in a sitting position to squats or back-kicks in a standing position, or push-ups,
or hip-raises in a recumbent position on a mat. Aerobic exercise included stepping,
simple walking, and zigzag walking with cones.

In the sessions for the DT group, concurrent cognitive tasks were performed during
resistance training and aerobic exercise. For instance, arithmetic tasks (subtraction
of one digit) or Shiritori, a Japanese word chain game in which one player has to
say a word starting with the last character of the word given by the previous player,
was carried out during thigh-raises. Otherwise, the subjects switched direction, walking
either forward or backward, according to the patterns of whistling. On the other hand,
the subjects in the ST group received simple resistance and aerobic training.

The Modified Mini-Mental State (3MS) examination

Cognitive assessment for all subjects was conducted using the Japanese version of
the 3MS examination, which was faithfully translated from the original developed by
Teng 11]. The 3MS exam comprises 15 questions, which are categorized into 8 domains, i.e.,
“registration recall” (immediately and delayed), “long-term memory” (date and place
of birth), “orientation” (temporal and spatial), “attention” (mental reversal), “verbal
fluency understanding” (naming, repetition and writing a sentence, reading and obeying
an order, three-stage command), “word retrieval” (four-legged animals), “visuospatial
skills” (copying two pentagons), and “similarities” (a point in common between two
words). We graded each domain, as well as the total scores (full marks?=?100), of
the 3MS exam.

Trail-Making Test (TMT)

The Trail-Making Test (TMT) was performed for the purpose of evaluating visual information
processing speed. In general, the TMT comprises asking a subject to draw a line connecting
25 consecutive circled numbers sequentially as quickly as possible. We enabled easier
and more systematic test processing by using a dedicated device for TMT with a touch
panel (Nounenreikei ATMT, elk Corp, Tokyo, Japan), in which a subject could pick the
targeted circled number by touching it instead of drawing a line. In the setting of
the device, circled numbers were laid out fixed on the liquid crystal display screen,
and the touched number was immediately deleted and a new one added each time a subject
touched a number. The time taken in seconds to complete all 25 numbers was calculated
automatically and used as the result.

Physiological performance

We assessed isometric muscle strength of quadriceps using the strain gauge dynamometer
(ST-200S, MULTECH, Japan). The subjects first sat on a chair with their hips and knees
flexed at 90° and their thighs fixed to the chair using the seat belt. Then they wore
the strap attached to the dynamometer round their ankles and tried to exert maximal
isometric knee extension. They performed two trials in each leg and the maximum value
was adopted.

To quantify motor ability, the functional tests were performed; maximal step length
(MSL), the Timed Up Go (TUG) test, and single leg standing. MSL was measured as
the maximum possible length of the subject’s stride of one step. In the TUG test,
we measured the time required for a subject to stand up from a chair, walk a distance
of 3 m, turn, walk back to the chair, and sit down. We also measured the maximum time
a subject could stand on one leg. In cases where a subject was able to continue single-leg
standing for over 120 s, the test was completed at that point. These functional tests
were each performed twice, and the best values were adopted.

Anthropometry

Body mass index (BMI) was calculated as body weight?×?(height)^?2 and expressed in kilograms per square meter. Percentages of body fat and muscle mass
of lower extremities were estimated by bioelectrical impedance analysis using the
body composition analyzer (Nippon Shooter Ltd., Physion MD, Tokyo, Japan).

Laboratory measurements and evaluation of insulin sensitivity

Blood samples were collected after a 12-hour overnight fast. Plasma glucose levels
were measured by the hexokinase UV method and serum insulin levels by chemiluminescent
enzyme immunoassay. We calculated the homeostasis model assessment of insulin resistance
(HOMA-IR), an established surrogate index of insulin resistance 12]. The HOMA-IR was obtained from fasting plasma glucose (FPG) and serum insulin (FIRI)
levels according to the original method by Matthews et al. 13], with the following formula:

HOMA-IR?=?FPG in mg/dl?×?FIRI in ?U/ml/405

A greater HOMA-IR represents a higher insulin resistance.

Plasma A? 40 and 42 levels were measured by a commercially available enzyme-linked
immunosorbent assay kit (#298-64601 for A? 40 and #296-64401 for A? 42, Wako, Osaka,
Japan). Regarding the test performance of the kit, the sensitivity was 0.019 pmol/l
(dynamic range, 1.0–100 pmol/l) for A? 40 and 0.06 pmol/l (dynamic range, 0.1–20 pmol/l)
for A? 42. The inter- and intraassay coefficients of variation were less than 10 %.

Statistical analysis

Comparisons of mean values at baseline and after the intervention between groups were
performed by unpaired t-test. The changes in clinical parameters following intervention in each group were
examined by paired t-test. Comparisons of the absolute changes in scores in the 3MS exam and each of its
domains, following intervention, were also performed by unpaired t-test. All statistical procedures were performed using SPSS (IBM, NY, US) for Windows
(Microsoft Inc. WA, US). P values less than 0.05 were considered statistically significant.
Ninety-five percent of confidence intervals (95 % CI) were calculated to estimate
the strength of the association when the p value for the group comparison was significant.