Exercise and Brain Vascular Function

Study Overview
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Brief Summary
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Cognitive performance is negatively related to an impaired glucose metabolism, possibly due to impairments in brain vascular function. Supported by the statement from the American Heart and Stroke Association that physical exercise is one of the most effective strategies to protect against cognitive decline, we now hypothesize that exercise-induced changes in glucose metabolism cause beneficial effects on brain vascular function thereby improving cognitive performance. The primary objective of this intervention study is thus to evaluate in sedentary elderly men the effect of a 8-week aerobic-based exercise program on cerebral blood flow, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI) perfusion method Arterial Spin Labeling (ASL). Cerebral blood flow is a robust and sensitive physiological marker of brain vascular function. Secondary objectives are to examine effects on glucose metabolism using the oral glucose tolerance test and cognitive performance as assessed with a neurophysiological test battery.

Official Title
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The Effects of Aerobic-based Exercise on Brain Vascular Function in Elderly Men

Conditions
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Physical Exercise, Cerebrovascular Function, Cerebral Blood Flow, Glucose Metabolism, Cognitive Performance

Intervention / Treatment
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* Other: Aerobic-based exercise program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 60-70 years Men BMI between 25-35 kg/m2 (overweight and slightly obese) Sedentary (not moderately active for 3 times or more per week) Fasting plasma glucose < 7.0 mmol/L Fasting serum total cholesterol < 8.0 mmol/L Fasting serum triacylglycerol < 4.5 mmol/L Systolic blood pressure < 160 mmHg and diastolic blood pressure < 100 mmHg Stable body weight (weight gain or loss < 3 kg in the past three months) Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study No difficult venipuncture as evidenced during the screening visit Exclusion Criteria: Women Current smoker, or smoking cessation < 12 months Diabetic patients Familial hypercholesterolemia Abuse of drugs More than 3 alcoholic consumptions per day Use of dietary supplements known to interfere with the main study outcomes as judged by the principal investigators Use medication to treat blood pressure, lipid or glucose metabolism Use of an investigational product within another biomedical intervention trial within the previous 1-month Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident Contra-indications for MRI imaging (e.g. pacemaker, surgical clips/material in body, metal splinter in eye, claustrophobia)

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will follow in randomized order a tightly controlled, progressive, aerobic-based exercise program or control program for eight weeks, separated by a washout period of twelve weeks.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic-based exercise program<br> | Other: Aerobic-based exercise program<br>* Aerobic-based exercise will be carried out on a cycling ergometer three times a week for 30 minutes at 70% of the maximal workload. Every two weeks, the maximal workload will be reassessed, and training loads will be readjusted accordingly. Fully supervised training sessions will be performed with three-to-four study participants at a time. Subjects should maintain their body weight during the intervention period.<br>|
| No Intervention: Control program<br>Maintenance of habitual physical activity levels | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain vascular function | Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL) | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose metabolism | Oral Glucose Tolerance Test (OGTT) | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | 
| Cognitive performance | Cambridge Neuropsychological Test Automated Battery (CANTAB) | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program |