Metabolic syndrome (MetS) is a risk for many chronic diseases of middle-aged and older adults. Hence, prevention and treatment of MetS is a crucial global health issue. However, it remains unclear regarding the cognitive effects and associated neural mechanisms of exercise interventions in this population. Therefore, the aims of this three-year project are to compare the effects and neural mechanism of three different types of exercise interventions, on components of MetS, as well as neuropsychological and physical functions in middle-aged and older adults with MetS.

This three-year study is an assessor-blind randomized controlled clinical trial. Another 67 middle-aged and older adults with MetS without regular exercise habits will be recruited and randomly assigned into the combined aerobic and resistance training (AT/RT) or Control (stretching and breathing exercise, ST/BR) group. All participants will undertake three one-hour sessions of exercises for 12 weeks, being supervised . Participants will also wear a wearable device that monitors, records, and provides feedback about their physical activity levels and heart rates during the entire 12 weeks. The outcome measures include participants's components of MetS and performance on neuropsychological and physical tests and structural and functional brain imaging parameters collected at pre-training, and post-training (week 12) tests. The investigators will compare the differences on all of these outcome measures and analyze the relationships between changes in brain structure and functional activation in relationship with other outcome measures in order to understand the neural mechanisms of the training effects and the differences in these mechanisms between the two groups.

Results of this study will provide important scientific evidence and clinical decision bases for determining effective exercise interventions in preventing the progression of MetS, improving neuropsychological and physical functions of MetS, as well as elucidating the neural mechanisms underlying these improvements.

Inclusion Criteria:

• Age between 45 and 80 years old
• Literacy
• Diagnosed with MetS based on the International Diabetes Federation (IDF) definition (Alberti et al., 2006) The IDF definition of MetS includes central obesity, determined by waist circumference at the midpoint between the lowest rib and iliac crest being ≧ 90 cm for men and ≧ 80 cm for women, plus at least two of the following conditions- (a) TG ≧ 150 mg/dl or being treated for this lipid abnormality, (b) HDL-C < 40 mg/dl in men, < 50 mg/dl in women, or being treated for this lipid abnormality, (c) systolic blood pressure (SBP) ≧ 130 mmHg, or systolic blood pressure (DBP) ≧ 85 mmHg, or being treated for diagnosed hypertension, and (d) FPG ≧ 100 mg/dl or diagnosed Type II DM).
• Living with a sedentary lifestyle (defined as being engaged in physical activities for less than a total of 90 minutes per week) (Fletcher et al., 1996) in recent one year.

Exclusion Criteria:

• Having any contraindications for fMRI (e.g., claustrophobia and indwelling metals or implanted devices)
• Serious or uncontrolled cardiovascular or pulmonary conditions (e.g., unstable angina, serious cardiac arrhythmias, heart failure, hypertrophic cardiomyopathy, severe aortic or carotid stenosis, pulmonary embolus or infarction, resting SBP ≥ 180 mmHg, or resting DBP ≥ 110 mmHg)
• Severe renal failure (Stages 4 and 5 of chronic kidney diseases (Levin et al., 2013)
• Symptoms or histories of neurological diseases, including transient ischemic attack
• Severe musculoskeletal disorders which would affect their mobility
• Diagnosis of dementia, Montreal Cognitive Assessment (MoCA) (Taiwan version) < 22 (Tsai et al., 2012; Wang et al., 2013), or inability to follow instructions
• Psychiatric disorders (including depression) or Geriatric Depression Scale-short form (GDS-15) score≧8 (Sheikh & Yesavage, 1986)
• Having contraindications for doing exercises (e.g., resting SBP ≥ 180 mmHg, resting DBP ≥ 110 mmHg, FPG ≥ 300 mg/dL, hypoglycemia (plasma glucose ≤ 70 mg/dL) after exercises, or postural hypotension (BP drop ≥ 20 mmHg when changing postures)
• Life expectancy less than six months due to any disease.