Lifestyle 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 a healthy lifestyle is one of the most effective strategies to protect against cognitive decline, the investigators now hypothesise that healthy lifestyle intervention-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 older men and women the effect of a 16-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 homeostatic model assessment for insulin resistance (HOMA-ir) and cognitive performance as assessed with a neurophysiological test battery.

Official Title
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The Effects of a Healthy Lifestyle Intervention on Brain Vascular Function in Older People

Conditions
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Healthy Lifestyle, Physical Exercise, Healthy Diet, Cerebrovascular Circulation, Cerebral Blood Flow, Glucose Metabolism, Cognitive Performance

Intervention / Treatment
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* Other: Healthy Lifestyle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 25-35 kg/m2 Sedentary (assessed as low physically active using the International Physical Activity Questionnaire) Right handedness and footedness 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: Current smoker, or smoking cessation < 12 months Diabetic patients Familial hypercholesterolemia Abuse of drugs Consumption of more than 21 alcoholic units/week (men), or more than 14 alcoholic units/week (women) 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, including permanent facial makeup, surgical clips/material in body, metal splinter in eye or claustrophobia

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy lifestyle<br>Healthy lifestyle intervention, which includes physical activity and dietary advice according to the dutch guidelines. | Other: Healthy Lifestyle<br>* The physical activity guidelines for older consist of 150 minutes per week moderate-to-high intensity exercise, two times per week muscle and bone strengthening exercises, which are combined with balance exercises. Additional health benefits can be achieved with a longer exercise duration, frequency and/or intensity. Furthermore, the amount of time sitting should be minimised. The dietary guidelines are described in detail in the so-called The Wheel of Five. In brief, the circle is divided into four food groups and one beverage group. More than half of the circle is covered by fruits, vegetables, whole grain (containing) breads, cereals and potatoes. A much smaller part is compromised by animal source foods, spreads and cooking fats. Water, tea and coffee without sugar complete the circle.<br>|
| No Intervention: Control<br>Maintenance of habitual physical activity and diet | |

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) | Baseline (0 weeks) | 
| Brain vascular function | Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL) | After intervention (16 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance | Cambridge Neuropsychological Test Automated Battery (CANTAB) | Baseline (0 weeks) and after intervention (16 weeks) | 
| Glucose metabolism | Homeostatic Model Assessment for Insulin Resistance (HOMA-ir) and HbA1c | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) |