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1.  Hertfordshire sarcopenia study: design and methods 
BMC Geriatrics  2010;10:43.
Background
Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms.
Methods
One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study.
Discussion
The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.
doi:10.1186/1471-2318-10-43
PMCID: PMC2909243  PMID: 20587018
2.  Effect of High- versus Low-Intensity Supervised Aerobic and Resistance Training on Modifiable Cardiovascular Risk Factors in Type 2 Diabetes; The Italian Diabetes and Exercise Study (IDES) 
PLoS ONE  2012;7(11):e49297.
Background
While current recommendations on exercise type and volume have strong experimental bases, there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes.
Objective
To compare the effects of moderate-to-high intensity (HI) versus low-to-moderate intensity (LI) training of equal energy cost, i.e. exercise volume, on modifiable cardiovascular risk factors.
Design
Pre-specified sub-analysis of the Italian Diabetes and Exercise Study (IDES), a randomized multicenter prospective trial comparing a supervised exercise intervention with standard care for 12 months (2005–2006).
Setting
Twenty-two outpatient diabetes clinics across Italy.
Patients
Sedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling (n = 303).
Interventions
Subjects were randomized by center to LI (n = 142, 136 completed) or HI (n = 161, 152 completed) progressive aerobic and resistance training, i.e. at 55% or 70% of predicted maximal oxygen consumption and at 60% or 80% of predicted 1-Repetition Maximum, respectively, of equal volume.
Main Outcome Measure(s)
Hemoglobin (Hb) A1c and other cardiovascular risk factors; 10-year coronary heart disease (CHD) risk scores.
Results
Volume of physical activity, both supervised and non-supervised, was similar in LI and HI participants. Compared with LI training, HI training produced only clinically marginal, though statistically significant, improvements in HbA1c (mean difference −0.17% [95% confidence interval −0.44,0.10], P = 0.03), triglycerides (−0.12 mmol/l [−0.34,0.10], P = 0.02) and total cholesterol (−0.24 mmol/l [−0.46, −0.01], P = 0.04), but not in other risk factors and CHD risk scores. However, intensity was not an independent predictor of reduction of any of these parameters. Adverse event rate was similar in HI and LI subjects.
Conclusions
Data from the large IDES cohort indicate that, in low-fitness individuals such as sedentary subjects with type 2 diabetes, increasing exercise intensity is not harmful, but does not provide additional benefits on cardiovascular risk factors.
Trial Registration
www.ISRCTN.org ISRCTN-04252749.
doi:10.1371/journal.pone.0049297
PMCID: PMC3504024  PMID: 23185314
3.  Protocol for: Sheffield Obesity Trial (SHOT): A randomised controlled trial of exercise therapy and mental health outcomes in obese adolescents [ISRCNT83888112] 
BMC Public Health  2005;5:113.
Background
While obesity is known to have many physiological consequences, the psychopathology of this condition has not featured prominently in the literature. Cross-sectional studies have indicated that obese children have increased odds of experiencing poor quality of life and mental health. However, very limited trial evidence has examined the efficacy of exercise therapy for enhancing mental health outcomes in obese children, and the Sheffield Obesity Trial (SHOT) will provide evidence of the efficacy of supervised exercise therapy in obese young people aged 11–16 years versus usual care and an attention-control intervention.
Method/design
SHOT is a randomised controlled trial where obese young people are randomised to receive; (1) exercise therapy, (2) attention-control intervention (involving body-conditioning exercises and games that do not involve aerobic activity), or (3) usual care. The exercise therapy and attention-control sessions will take place three times per week for eight weeks and a six-week home programme will follow this. Ninety adolescents aged between 11–16 years referred from a children's hospital for evaluation of obesity or via community advertisements will need to complete the study. Participants will be recruited according to the following criteria: (1) clinically obese and aged 11–16 years (Body Mass Index Centile > 98th UK standard) (2) no medical condition that would restrict ability to be active three times per week for eight weeks and (3) not diagnosed with insulin dependent diabetes or receiving oral steroids. Assessments of outcomes will take place at baseline, as well as four (intervention midpoint) and eight weeks (end of intervention) from baseline. Participants will be reassessed on outcome measures five and seven months from baseline. The primary endpoint is physical self-perceptions. Secondary outcomes include physical activity, self-perceptions, depression, affect, aerobic fitness and BMI.
doi:10.1186/1471-2458-5-113
PMCID: PMC1310532  PMID: 16259624
4.  Promotion of the mind through exercise (PROMoTE): a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment 
BMC Neurology  2010;10:14.
Background
Sub-cortical vascular ischaemia is the second most common etiology contributing to cognitive impairment in older adults, and is frequently under-diagnosed and under-treated. Although evidence is mounting that exercise has benefits for cognitive function among seniors, very few randomized controlled trials of exercise have been conducted in populations at high-risk for progression to dementia. Aerobic-based exercise training may be of specific benefit in delaying the progression of cognitive decline among seniors with vascular cognitive impairment by reducing key vascular risk factors associated with metabolic syndrome. Thus, we aim to carry out a proof-of-concept single-blinded randomized controlled trial primarily designed to provide preliminary evidence of efficacy aerobic-based exercise training program on cognitive and everyday function among older adults with mild sub-cortical ischaemic vascular cognitive impairment.
Methods/Design
A proof-of-concept single-blinded randomized trial comparing a six-month, thrice-weekly, aerobic-based exercise training group with usual care on cognitive and everyday function. Seventy older adults who meet the diagnostic criteria for sub-cortical ischaemic vascular cognitive impairment as outlined by Erkinjuntti and colleagues will be recruited from a memory clinic of a metropolitan hospital. The aerobic-based exercise training will last for 6 months. Participants will be followed for an additional six months after the cessation of exercise training.
Discussion
This research will be an important first step in quantifying the effect of an exercise intervention on cognitive and daily function among seniors with sub-cortical ischaemic vascular cognitive impairment, a recognized risk state for progression to dementia. Exercise has the potential to be an effective, inexpensive, and accessible intervention strategy with minimal adverse effects. Reducing the rate of cognitive decline among seniors with sub-cortical ischaemic vascular cognitive impairment could preserve independent functioning and health related quality of life in this population. This, in turn, could lead to reduced health care resource utilization costs and avoidance of early institutional care.
Trial Registration
ClinicalTrials.gov Protocol Registration System: NCT01027858.
doi:10.1186/1471-2377-10-14
PMCID: PMC2830197  PMID: 20158920
5.  The Effect of a Self Exercise Program in Cardiac Rehabilitation for Patients with Coronary Artery Disease 
Annals of Rehabilitation Medicine  2011;35(3):381-387.
Objective
To investigate the effect of self exercise in cardiac rehabilitation on cardiopulmonary exercise capacity for selected patients with coronary artery disease.
Method
The subjects of this study were patients who received percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery and who participated in a cardiac rehabilitation program. The supervised exercise group participated in 6-8 weeks of aerobic exercise training with telemetry ECG monitoring in hospital. The self exercise group, whose exercise risk was low, was instructed to participiate in self exercise training in a community exercise environment according to the exercise tolerance test (ETT) using a modified Bruce protocol. Both groups underwent ETTs before and 6 months after initiation of the cardiac rehabilitation program. We compared the supervised group with the self exercise groups on exercise capacity.
Results
After 6 months, the supervised exercise group showed significant changes in maximum oxygen consumption, maximal heart rate, resting heart rate, and submaximal rate pressure product. The self exercise group also showed significant improvement of maximum oxygen consumption and submaximal rate pressure product. However, the changing rate of maximum oxygen consumption was significantly higher in the supervised exercise group than the self exercise group.
Conclusion
Both the supervised and self exercise groups showed similar improvement of cardiopulmonary exercise capacity after 6 months' participation in the cardiac rehabilitation program. However, the changing rate of maximum oxygen consumption, maximal heart rate, and resting heart rate were significantly higher in the supervised exercise group than the self exercise group.
doi:10.5535/arm.2011.35.3.381
PMCID: PMC3309221  PMID: 22506148
Coronary artery disease; Exercise; Rehabilitation; Self
6.  Efficacy and Safety of Exercise Training in Patients With Chronic Heart Failure: HF-ACTION Randomized Controlled Trial 
Context
Guidelines recommend that exercise training be considered for medically stable outpatients with heart failure. Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes.
Objective
To test the efficacy and safety of exercise training among patients with heart failure.
Design, Setting, and Patients
Multicenter, randomized controlled trial among 2331 medically stable outpatients with heart failure and reduced ejection fraction. Participants in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) were randomized from April 2003 through February 2007 at 82 centers within the United States, Canada, and France; median follow-up was 30 months.
Interventions
Usual care plus aerobic exercise training, consisting of 36 supervised sessions followed by home-based training, or usual care alone.
Main Outcome Measures
Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or heart failure hospitalization.
Results
The median age was 59 years, 28% were women, and 37% had New York Heart Association class III or IV symptoms. Etiology was ischemic in 51%. Median left ventricular ejection fraction was 25%. Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12. A total of 759 (65%) patients in the exercise group died or were hospitalized, compared with 796 (68%) in the usual care group (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.84–1.02; P = .13). There were nonsignificant reductions in the exercise training group for mortality (189 [16%] in the exercise group vs 198 [17%] in the usual care group; HR, 0.96; 95% CI, 0.79–1.17; P = .70), cardiovascular mortality or cardiovascular hospitalization (632 [55%] in the exercise group vs 677 [58%] in the usual care group; HR, 0.92; 95% CI, 0.83–1.03; P = .14), and cardiovascular mortality or heart failure hospitalization (344 [30%] in the exercise group vs 393 [34%] in the usual care group; HR, 0.87; 95% CI, 0.75–1.00; P = .06). In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics, the HRs were 0.89 (95% CI, 0.81–0.99; P = .03) for all-cause mortality or hospitalization, 0.91 (95% CI, 0.82–1.01; P = .09) for cardiovascular mortality or cardiovascular hospitalization, and 0.85 (95% CI, 0.74–0.99; P = .03) for cardiovascular mortality or heart failure hospitalization. Other adverse events were similar between the groups.
Conclusions
In the protocol-specified primary analysis, exercise training resulted in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points. After adjustment for highly prognostic predictors of the primary end point, exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization.
Trial Registration
clinicaltrials.gov Identifier: NCT00047437
doi:10.1001/jama.2009.454
PMCID: PMC2916661  PMID: 19351941
7.  DEMO-II Trial. Aerobic Exercise versus Stretching Exercise in Patients with Major Depression—A Randomised Clinical Trial 
PLoS ONE  2012;7(10):e48316.
Background
The effect of referring patients from a clinical setting to a pragmatic exercise intervention for depressive symptoms, cognitive function, and metabolic variables has yet to be determined.
Methods
Outpatients with major depression (DSM-IV) were allocated to supervised aerobic or stretching exercise groups during a three months period. The primary outcome was the Hamilton depression score (HAM-D17). Secondary outcomes were cognitive function, cardiovascular risk markers, and employment related outcomes.
Results
56 participants were allocated to the aerobic exercise intervention versus 59 participants to the stretching exercise group. Post intervention the mean difference between groups was −0.78 points on the HAM-D17 (95% CI −3.2 to 1.6; P = .52). At follow-up, the participants in the aerobic exercise group had higher maximal oxygen uptake (mean difference 4.4 l/kg/min; 95% CI 1.7 to 7.0; P = .001) and visuospatial memory on Rey’s Complex Figure Test (mean difference 3.2 points; 95% CI 0.9 to 5.5; P = .007) and lower blood glucose levels (mean difference 0.2 mmol/l; 95% CI 0.0 to 0.5; P = .04) and waist circumference (mean difference 2.2 cm; 95% CI 0.3 to 4.1; P = .02) compared with the stretching exercise group.
Conclusions
The results of this trial does not support any antidepressant effect of referring patients with major depression to a three months aerobic exercise program. Due to lower recruitment than anticipated, the trial was terminated prior to reaching the pre-defined sample size of 212 participants; therefore the results should be interpreted in that context. However, the DEMO-II trial does suggest that an exercise program for patients with depression offer positive short-term effects on maximal oxygen uptake, visuospatial memory, fasting glucose levels, and waist circumference.
Trial Registration
ClinicalTrials.gov NCT00695552
doi:10.1371/journal.pone.0048316
PMCID: PMC3485141  PMID: 23118981
8.  Exercise in pregnant women and birth weight: a randomized controlled trial 
Background
Birth weight plays an important role in infant mortality and morbidity, childhood development, and adult health. To date there are contradictory results regarding the role of physical activity on birth weight. In addition, it is questioned whether exercise during second and third trimesters of pregnancy might affect gestational age and increase the risk of preterm delivery. Hence, the purpose of this study was to examine the effect of a supervised exercise-program on birth weight, gestational age at delivery and Apgar-score.
Methods
Sedentary, nulliparous pregnant women (N = 105), mean age 30.7 ± 4.0 years, pre-pregnancy BMI 23.8 ± 4.3 were randomized to either an exercise group (EG, n = 52) or a control group (CG, n = 53). The exercise program consisted of supervised aerobic dance and strength training for 60 minutes, twice per week for a minimum of 12 weeks, with an additional 30 minutes of self-imposed physical activity on the non-supervised week-days.
Results
There was no statistically significant difference between groups in mean birth weight, low birth weight (< 2500 g) or macrosomia (≥ 4000 g). Per protocol analyses showed higher Apgar score (1 min) in the EG compared with the CG (p = 0.02). No difference was seen in length of gestation.
Conclusion
Aerobic-dance exercise was not associated with reduction in birth weight, preterm birth rate or neonatal well-being.
Trial Registration
ClinicalTrials.gov: NCT00617149
doi:10.1186/1471-2393-11-66
PMCID: PMC3198740  PMID: 21961534
9.  The effects of a home-based arm ergometry exercise programme on physical fitness, fatigue and activity in polio survivors: protocol for a randomised controlled trial 
BMC Neurology  2012;12:157.
Background
Many Polio survivors have reduced mobility, pain and fatigue, which make access to conventional forms of aerobic exercise difficult. Inactivity leads to increased risk of health problems, many of which are prevalent among Polio survivors. Aerobic exercise programmes in Polio survivors should utilise stable muscle groups and should be designed to minimise exacerbation of pain and fatigue. A home-based arm ergometry aerobic exercise programme may represent an affordable and accessible exercise modality, incorporating exercise prescription principles in this group.
Methods/design
This is a prospective, single blinded, randomised controlled trial. There are two arms; exercise intervention using arm ergometers and control. Polio survivors meeting eligibility criteria will be recruited and randomly allocated to intervention or control groups. Participants allocated to the intervention group will receive a small arm ergometer and a polar heart rate monitor. They will carry out a home-based moderate intensity (50-70% HRMax) aerobic exercise programme for eight weeks, following instruction by the treating physiotherapist. Assessments will occur at baseline and after eight weeks and will include tests of physical fitness, activity, energy cost of walking, fatigue and quality of life. Clinically feasible assessment tools including the Six Minute Arm Test, the Physical Activity Scale for People with Physical Disabilities questionnaire, the Physiological Cost Index, Fatigue Severity Scale and the SF-36v2 will be utilised.
Discussion
The efficacy of a home-based arm ergometry programme in Polio survivors will be examined. No previous trial has examined such a programme using a wide range of outcome measures pertinent to Polio survivors. This study will provide new information on the impact of arm ergometry on physical fitness, activity, body composition, fatigue, pain, muscle strength, and health related quality of life. Also, the study will provide information, which at present is lacking, on safety of aerobic exercise in Polio, as potential negative outcomes of activity including loss of muscle strength, increased pain and fatigue will be closely monitored.
Trial registration
Clinicaltrials.gov identifier: NCT01271530
doi:10.1186/1471-2377-12-157
PMCID: PMC3553047  PMID: 23234560
Poliomyelitis; Arm Ergometry; Physical fitness; Fatigue
10.  Effects of multicomponent exercise on cognitive function in older adults with amnestic mild cognitive impairment: a randomized controlled trial 
BMC Neurology  2012;12:128.
Background
To examine the effects of a multicomponent exercise program on the cognitive function of older adults with amnestic mild cognitive impairment (aMCI).
Methods
Design: Twelve months, randomized controlled trial; Setting: Community center in Japan; Participants: Fifty older adults (27 men) with aMCI ranging in age from 65 to 93 years (mean age, 75 years); Intervention: Subjects were randomized into either a multicomponent exercise (n = 25) or an education control group (n = 25). Subjects in the multicomponent exercise group exercised under the supervision of physiotherapists for 90 min/d, 2 d/wk, for a total of 80 times over 12 months. The exercises included aerobic exercises, muscle strength training, and postural balance retraining, and were conducted using multiple conditions to stimulate cognitive functions. Subjects in the control group attended three education classes regarding health during the 12-month period. Measurements were administered before, after the 6-month, and after the 12-month intervention period; Measurements: The performance measures included the mini-mental state examination, logical memory subtest of the Wechsler memory scale-revised, digit symbol coding test, letter and categorical verbal fluency test, and the Stroop color word test.
Results
The mean adherence to the exercise program was 79.2%. Improvements of cognitive function following multicomponent exercise were superior at treatment end (group × time interactions for the mini-mental state examination (P = 0.04), logical memory of immediate recall (P = 0.03), and letter verbal fluency test (P = 0.02)). The logical memory of delayed recall, digit symbol coding, and Stroop color word test showed main effects of time, although there were no group × time interactions.
Conclusions
This study indicates that exercise improves or supports, at least partly, cognitive performance in older adults with aMCI.
doi:10.1186/1471-2377-12-128
PMCID: PMC3534485  PMID: 23113898
Aerobic exercise; MCI; Elderly; Alzheimer’s disease; Prevention
11.  Beneficial effects of short-term combination exercise training on diverse cognitive functions in healthy older people: study protocol for a randomized controlled trial 
Trials  2012;13:200.
Background
Results of previous studies have shown that exercise training can improve cognitive functions in healthy older people. Some studies have demonstrated that long-term combination exercise training can facilitate memory function improvement better than either aerobic or strength exercise training alone. Nevertheless, it remains unclear whether short-term combination exercise training can improve diverse cognitive functions in healthy older people or not. We investigate the effects of four weeks of short-term combination exercise training on various cognitive functions (executive functions, episodic memory, short-term memory, working memory, attention, reading ability, and processing speed) of healthy older people.
Methods
A single-blinded intervention with two parallel groups (combination exercise training; waiting list control) is used. Testers are blind to the study hypothesis and the participants’ group membership. Through an advertisement in a local newspaper, 64 healthy older adults are recruited and then assigned randomly to a combination exercise training group or a waiting list control group. Participants in the combination exercise training group must participate in the short-term combination exercise training (aerobic and strength exercise training) three days per week during the four weeks (12 workouts in total). The waiting list group does not participate in the combination exercise training. The primary outcome measure is the Stroop test score: a measure of executive function. Secondary outcome measures are assessments including the Verbal Fluency Task, Logical Memory, First and Second Names, Digit Span Forward, Digit span backward, Japanese Reading Test, Digit Cancellation Task, Digit Symbol Coding, and Symbol Search. We assess these outcome measures before and after the intervention.
Discussion
This report is the first of a study that investigates the beneficial effects of short-term combination exercise training on diverse cognitive functions of older people. Our study is expected to provide sufficient evidence of short-term combination exercise’s effectiveness.
Trial registration
This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (Number UMIN000007828).
doi:10.1186/1745-6215-13-200
PMCID: PMC3495024  PMID: 23107038
12.  Exercise for Adolescents with Depressive Disorders: A Feasibility Study 
Objectives. Adolescence is associated with increased depressive symptoms and decreased aerobic exercise, yet the relationship between exercise and clinical depression among adolescents requires further examination. This study assessed the feasibility of a 12-week intervention designed to increase exercise for adolescents with depressive disorders: Will a teenager with depression exercise? Methods. Participants were 13 adolescents with depression reporting low levels of aerobic exercise. They completed a 12-week intervention (15 supervised exercise sessions and 21 independent sessions). Exercise was measured through the aerobic exercise Questionnaire, actigraphy, and heart-rate monitoring. Depression was measured with the Children's Depression Rating Scale, Revised, and Quick Inventory of Depressive Symptomatology, Self-Report. Results. All participants who started the intervention completed the protocol, attending all supervised exercise sessions. Actigraphy verified 81% adherence to the protocol's independent sessions. Analysis of secondary outcomes showed a significant increase in exercise levels and a significant decrease in depression severity. Initially, ten participants were overweight or obese, and three were healthy weight. After 12 weeks of exercise, the number of participants in the healthy-weight category doubled. Conclusions. Adolescents suffering from depression can complete a rigorous protocol requiring structured increases in aerobic exercise. Participants showed significant increases in exercise, and significant decreases in depressive symptoms.
doi:10.1155/2012/257472
PMCID: PMC3409521  PMID: 22888415
13.  Effects of Aerobic Exercise on Mild Cognitive Impairment 
Archives of neurology  2010;67(1):71-79.
Objectives
To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response.
Design
Six-month, randomized, controlled, clinical trial.
Setting
Veterans Affairs Puget Sound Health Care System clinical research unit.
Participants
Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years).
Intervention
Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered.
Main Outcome Measures
Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42.
Results
Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance.
Conclusions
This study provides support, using rigorous controlled methodology, for a potent nonpharma-cologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.
doi:10.1001/archneurol.2009.307
PMCID: PMC3056436  PMID: 20065132
14.  Extremely short duration high intensity interval training substantially improves insulin action in young healthy males 
Background
Traditional high volume aerobic exercise training reduces cardiovascular and metabolic disease risk but involves a substantial time commitment. Extremely low volume high-intensity interval training (HIT) has recently been demonstrated to produce improvements to aerobic function, but it is unknown whether HIT has the capacity to improve insulin action and hence glycemic control.
Methods
Sixteen young men (age: 21 ± 2 y; BMI: 23.7 ± 3.1 kg·m-2; VO2peak: 48 ± 9 ml·kg-1·min-1) performed 2 weeks of supervised HIT comprising of a total of 15 min of exercise (6 sessions; 4–6 × 30-s cycle sprints per session). Aerobic performance (250-kJ self-paced cycling time trial), and glucose, insulin and NEFA responses to a 75-g oral glucose load (oral glucose tolerance test; OGTT) were determined before and after training.
Results
Following 2 weeks of HIT, the area under the plasma glucose, insulin and NEFA concentration-time curves were all reduced (12%, 37%, 26% respectively, all P < 0.001). Fasting plasma insulin and glucose concentrations remained unchanged, but there was a tendency for reduced fasting plasma NEFA concentrations post-training (pre: 350 ± 36 v post: 290 ± 39 μmol·l-1, P = 0.058). Insulin sensitivity, as measured by the Cederholm index, was improved by 23% (P < 0.01), while aerobic cycling performance improved by ~6% (P < 0.01).
Conclusion
The efficacy of a high intensity exercise protocol, involving only ~250 kcal of work each week, to substantially improve insulin action in young sedentary subjects is remarkable. This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise regimes.
doi:10.1186/1472-6823-9-3
PMCID: PMC2640399  PMID: 19175906
15.  Research to Encourage Exercise for Fibromyalgia (REEF): Use of Motivational Interviewing Design and Method 
Contemporary clinical trials  2010;32(1):59-68.
Fibromyalgia (FM), defined as the presence of both chronic widespread pain and the finding of 11/18 tender points on examination, is an illness associated with major personal and societal burden. Supervised aerobic exercise is an important treatment modality to improve patient symptoms. Unfortunately, adherence to an exercise regimen after a structured supervised program is disappointingly low. Since FM is a chronic illness, studies are needed to test strategies that would enhance exercise adherence in these individuals. Individuals who are able to adhere to exercise almost always maintain the symptomatic benefits of exercise. The objective of this paper was to describe the protocol of the Research to Encourage Exercise for Fibromyalgia (REEF). REEF is a randomized attention-controlled trial that seeks to test the efficacy of 6 sessions of telephone delivered motivational interviewing (MI) that targets exercise adherence to improve FM-relevant clinical outcomes (i.e., physical function and pain severity). The trial has recently completed enrolling 216 subjects, and randomization has resulted in well balanced groups. Details on the study design, MI program, and treatment fidelity are provided in the paper. Outcome assessments at week 12, week 24 and week 36 will test the immediate, intermediate and long term effects of exercise-based MI on adherence (as measured by the Community Health Activities Model Program for Seniors/CHAMPS and accelerometer) and clinical outcomes. When completed, REEF will determine whether exercise-based MI could be utilized as a management strategy to sustain the clinical benefits of exercise for FM.
doi:10.1016/j.cct.2010.08.014
PMCID: PMC3005851  PMID: 20828634
Fibromyalgia; Exercise; Physical activity; Motivational interviewing; Physical function; Pain
16.  Exercise, Inflammation and Aging 
Aging and Disease  2011;3(1):130-140.
Aging results in chronic low grade inflammation that is associated with increased risk for disease, poor physical functioning and mortality. Strategies that reduce age-related inflammation may improve the quality of life in older adults. Regular exercise is recommended for older people for a variety of reasons including increasing muscle mass and reducing risk for chronic diseases of the heart and metabolic systems. Only recently has exercise been examined in the context of inflammation. This review will highlight key randomized clinical trial evidence regarding the influence of exercise training on inflammatory biomarkers in the elderly. Potential mechanisms will be presented that might explain why exercise may exert an anti-inflammatory effect.
PMCID: PMC3320801  PMID: 22500274
Aging; Exercise, Inflammation; Adipose; Elderly
17.  The effect of walking on falls in older people: the 'Easy Steps to Health' randomized controlled trial study protocol 
BMC Public Health  2011;11:888.
Background
Falls in older people continue to be a major public health issue in industrialized countries. Extensive research into falls prevention has identified exercise as a proven fall prevention strategy. However, despite over a decade of promoting physical activity, hospitalisation rates due to falls injuries in older people are still increasing. This could be because efforts to increase physical activity amongst older people have been unsuccessful, or the physical activity that older people engage in is insufficient and/or inappropriate. The majority of older people choose walking as their predominant form of exercise. While walking has been shown to lower the risk of many chronic diseases its role in falls prevention remains unclear. This paper outlines the methodology of a study whose aims are to determine: if a home-based walking intervention will reduce the falls rate among healthy but inactive community-dwelling older adults (65 + years) compared to no intervention (usual activity) and; whether such an intervention can improve risk factors for falls, such as balance, strength and reaction time.
Methods/Design
This study uses a randomised controlled trial design.
A total of 484 older people exercising less than 120 minutes per week will be recruited through the community and health care referrals throughout Sydney and neighboring regions. All participants are randomised into either the self-managed walking program group or the health-education waiting list group using a block randomization scheme.
Outcome measures include prospective falls and falls injuries, quality of life, and physical activity levels. A subset of participants (n = 194) will also receive physical performance assessments comprising of tests of dynamic balance, strength, reaction time and lower limb functional status.
Discussion
Certain types of physical activity can reduce the risk of falls. As walking is already the most popular physical activity amongst older people, if walking is shown to reduce falls the public health implications could be enormous. Conversely, if walking does not reduce falls in older people, or even puts older people at greater risk, then health resources targeting falls prevention need to be invested elsewhere.
Trial Registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000380099
doi:10.1186/1471-2458-11-888
PMCID: PMC3251253  PMID: 22115340
18.  Little evidence of systemic and adipose tissue inflammation in overweight individuals† 
Context: The effect of weight loss by diet alone or diet in conjunction with exercise on low-grade inflammation in non-obese (overweight) individuals is not known. Objective: Test the hypothesis that 24 weeks of moderate calorie restriction (CR; 25%) by diet only or with aerobic exercise would reduce markers of systemic inflammation and attenuate inflammation gene expression in subcutaneous adipose tissue. Design: Randomized controlled trial. Setting: Institutional Research Center. Participants: Thirty-five overweight (body mass index: 27.8 ± 0.7 kg/m2) but otherwise healthy participants (16M/19F) completed the study. Intervention: Participants were randomized to either CR (25% reduction in energy intake, n = 12), caloric restriction + exercise (CR + EX: 12.5% reduction in energy intake + 12.5% increase in exercise energy expenditure, n = 12), or control (healthy weight-maintenance diet, n = 11) for 6 months. Main outcome measures: Fasting serum markers of inflammation [leptin, highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin] and inflammation-related genes [CD68, IL-6, TNF-α, macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1), adiponectin, plasminogen activator inhibitor-1 (PAI-1)] in subcutaneous adipose tissue. Results: CR and CR + EX lost similar amounts of body weight (–10 ± 1%), fat mass (–24 ± 3%), visceral fat (–27 ± 3%), and had increased insulin sensitivity (CR: 40 ± 20%, CR + EX: 66 ± 22%). Leptin was significantly decreased from baseline (p < 0.001) in both groups however TNF-α and IL-6 were not changed. hsCRP was decreased in CR + EX. There was no change in the expression of genes involved in macrophage infiltration (CD68, MIF MCP-1, PAI-1) or inflammation (IL-6, TNF-α, adiponectin) in either CR or CR + EX. Conclusion: A 10% weight loss with a 25% CR diet alone or with exercise did not impact markers of systemic inflammation or the expression of inflammation-related adipose genes in overweight individuals.
doi:10.3389/fgene.2012.00058
PMCID: PMC3329711  PMID: 22529850
caloric restriction; inflammation; subcutaneous fat; exercise; aging; immune function
19.  Short-Term Aerobic Exercise Reduces Arterial Stiffness in Older Adults With Type 2 Diabetes, Hypertension, and Hypercholesterolemia 
Diabetes Care  2009;32(8):1531-1535.
OBJECTIVE
The relationship between increased arterial stiffness and cardiovascular mortality is well established in type 2 diabetes. We examined whether aerobic exercise could reduce arterial stiffness in older adults with type 2 diabetes complicated by comorbid hypertension and hyperlipidemia.
RESEARCH DESIGN AND METHODS
A total of 36 older adults (mean age 71.4 ± 0.7 years) with diet-controlled or oral hypoglycemic–controlled type 2 diabetes, hypertension, and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (3 months vigorous aerobic exercise) and a nonaerobic group (no aerobic exercise). Exercise sessions were supervised by a certified exercise trainer three times per week, and a combination of cycle ergometers and treadmills was used. Arterial stiffness was measured using the Complior device.
RESULTS
When the two groups were compared, aerobic training resulted in a decrease in measures of both radial (−20.7 ± 6.3 vs. +8.5 ± 6.6%, P = 0.005) and femoral (−13.9 ± 6.7 vs. +4.4 ± 3.3%, P = 0.015) pulse-wave velocity despite the fact that aerobic fitness as assessed by Vo2max did not demonstrate an improvement with training (P = 0.026).
CONCLUSIONS
Our findings indicate that a relatively short aerobic exercise intervention in older adults can reduce multifactorial arterial stiffness (type 2 diabetes, aging, hypertension, and hypercholesterolemia).
doi:10.2337/dc09-0149
PMCID: PMC2713633  PMID: 19509011
20.  Factors associated with symptoms of anxiety and depression in five cohorts of community-based older people: the HALCyon (Healthy Ageing across the Life Course) Programme 
Psychological medicine  2011;41(10):2057-2073.
Background
Symptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety.
Method
We used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme : the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each.
Results
Greater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life.
Conclusions
Anxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed.
doi:10.1017/S0033291711000195
PMCID: PMC3349051  PMID: 21349224
Anxiety; cohort studies; depression; elderly; life course
21.  A 19-week exercise program for people with chronic stroke enhances bone geometry at the tibia: a peripheral quantitative computed tomography study 
Introduction and Hypothesis
Regular skeletal-loading exercise is an effective intervention to improve bone health in older individuals. However, little is known about the bone responses to exercise in people with stroke. Following a stroke, muscle atrophy and bone loss occurs. Diminished areal bone mineral density combined with an increased number of falls substantially enhances the risk for a fragility fracture. We undertook a randomized controlled intervention trial to assess the impact of a 19-week comprehensive exercise program on lower extremity bone health in people with chronic stroke.
Methods
Sixty-three community-dwelling individuals with chronic stroke were randomly allocated to either an intervention group or a control group. The intervention group participated in a 19-week thrice-weekly exercise program consisting of skeletal-loading, aerobic, strengthening and balance exercises. The control group completed a seated upper extremity exercise program. We used peripheral quantitative computed tomography (pQCT) to measure bone geometry and volumetric bone mineral density at the distal 4% and midshaft 50% of the tibia before and after the intervention.
Results
Following the exercise program, the intervention group had significantly more percent gain in trabecular bone content at the 4% site on the paretic side than the control group (p=0.048). At the 50% site on the paretic side, the intervention group also had significantly greater percent gain in cortical thickness (p=0.026) but not the polar stress strain index (p-SSI) when compared with the control group. However, no significant between-group difference was found in trabecular bone density (4% site) and cortical bone density (50% site) percent gain on the paretic side. No significant changes were observed in any variables on the non-paretic side at the 4% or 50% site.
Conclusions
This study provided some evidence that the 19-week comprehensive exercise program could have a positive impact on bone parameters at the tibia for individuals with chronic stroke. However, a larger randomized controlled trial is required in the future to assess the impact of exercise on lower extremity bone health in the stroke population.
doi:10.1007/s00198-006-0168-0
PMCID: PMC3123335  PMID: 16896509 CAMSID: cams1781
Cerebrovascular accident; bone health; physical activity; rehabilitation; peripheral quantitative computed tomography
22.  Physical Exercise as a Preventive or Disease-Modifying Treatment of Dementia and Brain Aging 
Mayo Clinic Proceedings  2011;86(9):876-884.
A rapidly growing literature strongly suggests that exercise, specifically aerobic exercise, may attenuate cognitive impairment and reduce dementia risk. We used PubMed (keywords exercise and cognition) and manuscript bibliographies to examine the published evidence of a cognitive neuroprotective effect of exercise. Meta-analyses of prospective studies documented a significantly reduced risk of dementia associated with midlife exercise; similarly, midlife exercise significantly reduced later risks of mild cognitive impairment in several studies. Among patients with dementia or mild cognitive impairment, randomized controlled trials (RCTs) documented better cognitive scores after 6 to 12 months of exercise compared with sedentary controls. Meta-analyses of RCTs of aerobic exercise in healthy adults were also associated with significantly improved cognitive scores. One year of aerobic exercise in a large RCT of seniors was associated with significantly larger hippocampal volumes and better spatial memory; other RCTs in seniors documented attenuation of age-related gray matter volume loss with aerobic exercise. Cross-sectional studies similarly reported significantly larger hippocampal or gray matter volumes among physically fit seniors compared with unfit seniors. Brain cognitive networks studied with functional magnetic resonance imaging display improved connectivity after 6 to 12 months of exercise. Animal studies indicate that exercise facilitates neuroplasticity via a variety of biomechanisms, with improved learning outcomes. Induction of brain neurotrophic factors by exercise has been confirmed in multiple animal studies, with indirect evidence for this process in humans. Besides a brain neuroprotective effect, physical exercise may also attenuate cognitive decline via mitigation of cerebrovascular risk, including the contribution of small vessel disease to dementia. Exercise should not be overlooked as an important therapeutic strategy.
doi:10.4065/mcp.2011.0252
PMCID: PMC3258000  PMID: 21878600
23.  Testing the effectiveness of a self-efficacy based exercise intervention for inactive people with type 2 diabetes mellitus: design of a controlled clinical trial 
BMC Public Health  2012;12:331.
Background
Sufficient exercise is important for people with Type 2 Diabetes Mellitus (T2DM), as it can prevent future health problems. Despite, it is estimated that only 30-40% of people with T2DM are sufficiently active. One of the psychosocial constructs that is believed to influence physical activity behaviour, is exercise self-efficacy. The goal of this study is to evaluate a patient-tailored exercise intervention for people with T2DM that takes exercise self-efficacy into account.
Methods/Design
This study is conducted as a non-randomized controlled clinical trial. Patients are eligible when they are diagnosed with T2DM, exercise less than advised in the ADA guideline of 150 min/week of moderate-intensity aerobic physical activity, have an BMI >25 and are between 18 and 80 years old. Recruitment takes place at a Primary care organization of general practitioners and practice nurses in the south of the Netherlands.
Participants are allocated to three groups: An advice intervention -for participants with a high exercise self-efficacy score- in which participants receive a patient-tailored exercise intervention, an intensive intervention -for participants with a low exercise self-efficacy score- in which participants receive a patient-tailored exercise intervention accomplished by a group based intervention, and a control group in which participants receive regular Dutch diabetes care. The primary outcome measure of this study is physical activity. Secondary outcome measures are health status, (symptoms of) depression, exercise self-efficacy, Body Mass Index (BMI), blood pressure and glycemic control.
Discussion
We aimed to design an intervention that can be implemented in Primary care, but also to design an easy accessible program. This study is innovative as it is -to our best knowledge- the first study that takes level of exercise self-efficacy of people with T2DM into account by means of giving extra support to those with the lowest exercise self-efficacy. If the program succeeds in increasing the amount of physical activity it can be implemented in regular primary care.
Trial registration
Dutch Trial Register NTR2734
doi:10.1186/1471-2458-12-331
PMCID: PMC3390268  PMID: 22559322
24.  Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials 
Objective—To assess the effectiveness of exercise programmes in preventing falls (and/or lowering the risk of falls and fall related injuries) in older people.
Design—A review of controlled clinical trials designed with the aim of lowering the risk of falling and/or fall injuries through an exercise only intervention or an intervention that included an exercise component
Main outcome measures—Falls, fall related injuries, time between falls, costs, cost effectiveness.
Subjects—A total of 4933 men and women aged 60 years and older.
Results—Eleven trials meeting the criteria for inclusion were reviewed. Eight of these trials had separate exercise interventions, and three used interventions with an exercise programme component. Five trials showed a significant reduction in the rate of falls or the risk of falling in the intervention group.
Conclusions—Exercise is effective in lowering falls risk in selected groups and should form part of falls prevention programmes. Lowering fall related injuries will reduce health care costs but there is little available information on the costs associated with programme replication or the cost effectiveness of exercise programmes aimed at preventing falls in older people.
Key Words: exercise; elderly; falls; cost effectiveness
doi:10.1136/bjsm.34.1.7
PMCID: PMC1724164  PMID: 10690444
25.  Exercise and diet induced weight loss improves measures of oxidative stress and insulin sensitivity in adults with characteristics of the metabolic syndrome 
Obesity and insulin resistance (IR) increase the risk for coronary heart disease; however, much of this risk is not attributable to traditional risk factors. We sought to determine whether weight loss associated with supervised aerobic exercise beneficially alters biomarkers of oxidative stress and whether these alterations are associated with improvements in measures of insulin resistance. Twenty-five sedentary and overweight to obese [body mass index (BMI) = 33.0 ± 0.8 kg/m2] individuals, with characteristics of the metabolic syndrome, participated in a 4- to 7-mo weight loss program that consisted of energy restriction (reduced by ~500 kcal/day) and supervised aerobic exercise (5 days/wk, 45 min/day at 60% V̇o2max; ~375 kcal/day). IR and insulin sensitivity were assessed by the calculation of the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI), respectively. Oxidative stress was assessed by oxidized LDL (oxLDL), myeloperoxidase (MPO), and low- and high-density lipoprotein (LDL and HDL) lipid hydroperoxide concentrations in serum. Indexes for antioxidative status included apolipoprotein A1 (apoA1) concentrations and paraoxonase-1 (PON1) activity and protein concentrations. Exercise- and diet-induced weight loss (~10%) significantly (P < 0.05) increased insulin sensitivity and reduced IR, oxLDL, and LDL lipid hydroperoxides but did not alter HDL lipid hydroperoxides or MPO concentrations. Lifestyle modification impacted systemic antioxidative status by increasing apoA1 concentrations and reducing serum PON1 protein and activity. Changes in oxidative stress were not associated with alterations in HOMA or QUICKI. Diet- and exercise-induced weight loss (~10%) improves measures of insulin sensitivity and beneficially alters biomarkers of oxidative status.
doi:10.1152/ajpendo.00116.2007
PMCID: PMC2646852  PMID: 17473052
insulin resistance; oxidized low-density lipoprotein; paraoxonase-1; energy restriction

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