Cerebral Blood Flow, Cerebrovascular Function, Cognitive Performance, Glucose Metabolism, Physical Exercise
Conditions
Brief summary
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.
Interventions
OTHERAerobic-based exercise program
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.
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
MALE
Age
60 Years to 70 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain vascular function | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose metabolism | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Oral Glucose Tolerance Test (OGTT) |
| Cognitive performance | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Cambridge Neuropsychological Test Automated Battery (CANTAB) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Other physiological parameters: Advanced glycation endproducts | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Serum protein-bound advanced glycation endproducts (AGEs) |
| Other physiological parameters: Conventional metabolic risk markers | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Lipids and lipoproteins, glucose and insulin, and markers for low-grade systemic inflammation and microvascular function |
| Other perceivable benefits: Quality of Life | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | The Quality of life (QoL) will be assessed using a 32-item questionnaire |
| Other perceivable benefits: Sleep characteristics | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Sleep characteristics will be assessed using the 10-item Pittsburgh Sleep Quality Index |
| Other physiological parameters: Peripheral vascular function | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Flow-mediated vasodilation (FMD), carotid artery reactivity, pulse wave analysis (PWA) and velocity (PWV), and retinal images |
| Other perceivable benefits: Physical fitness (1) | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Incremental exhaustive exercise test (VO2 max) |
| Other perceivable benefits: Physical fitness (2) | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Timed up-and-go test (TUGT) |
| Other perceivable benefits: Physical fitness (3) | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | The 6-minute walk test (6 MWT) |
| Other perceivable benefits: Physical fitness (4) | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Handgrip and muscle strength tests |
| Other perceivable benefits: Mood | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Mood will be tested using the Affect Grid |
| Other physiological parameters: Blood pressure | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | Office and 24-hour ambulatory blood pressure |
| Other physiological parameters: Continuous blood glucose | Difference between outcomes at the end of an 8-week aerobic-based exercise and control program | 36-hour glycaemic response |
Countries
Netherlands
Outcome results
None listed