Cerebral Blood Flow, Cerebrovascular Circulation, Cognitive Performance, Glucose Metabolism, Healthy Diet, Healthy Lifestyle, 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 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.
Interventions
OTHERHealthy Lifestyle
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.
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain vascular function | Baseline (0 weeks) | Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose metabolism | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Homeostatic Model Assessment for Insulin Resistance (HOMA-ir) and HbA1c |
| Cognitive performance | Baseline (0 weeks) and after intervention (16 weeks) | Cambridge Neuropsychological Test Automated Battery (CANTAB) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Carotid Artery Reactivity (CAR) | Baseline (0 weeks) and after intervention (16 weeks) | Peripheral vascular function, endothelial function |
| Pulse Wave Analysis (PWA) | Baseline (0 weeks) and after intervention (16 weeks) | Peripheral vascular function, vascular stiffness |
| Pulse Wave Velocity (PWV) | Baseline (0 weeks) and after intervention (16 weeks) | Peripheral vascular function, vascular stiffness |
| Retinal microvascular calibers | Baseline (0 weeks) and after intervention (16 weeks) | Peripheral vascular function, microcirculation |
| Blood pressure (systolic, diastolic and mean pressure) | Baseline (0 weeks) and after intervention (16 weeks) | Office and 24-hour ambulatory blood pressure |
| Serum lipid profile concentration | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Concentration of serum lipids |
| Serum insulin concentration | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Concentration of insulin in serum |
| Plasma glucose concentration | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Concentration of glucose in plasma |
| Homeostatic Model Assessment for Insulin Resistance (HOMA-ir) | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | HOMA-ir is a method used to quantify insulin resistance and beta-cell function |
| Circulating markers for microvascular function | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Markers for microvascular function (sCAM-1, vWf, cGMP) |
| Circulating marker of neurogenesis | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Brain-derived neurotrophic factor (BDNF) |
| Glycated haemoglobin (HbA1C) | Baseline (0 weeks) and after intervention (16 weeks) | HbA1C is a form of hemoglobin (abbreviated Hb) that is chemically linked to a sugar. |
| Aerobic fitness | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Incremental exhaustive exercise test (Maximal oxygen consumption and power output) |
| Physical fitness (1) | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Incremental exhaustive exercise test (Maximal Power output) |
| Physical fitness (2) | Baseline (0 weeks) and after intervention (16 weeks) | The 6-minute walk test (6 MWT) |
| Activity monitoring | Baseline (0 weeks) and after intervention (16 weeks) for four consecutive days | activPAL activity monitor |
| Self reported physical activity | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | The International Physical Activity Questionnaire |
| Food frequency questionnaire | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Self reported food consumption |
| Dutch Healthy Diet index 2015 | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Compliance to the Dutch dietary guidelines based on the FFQ |
| Quality of Life score | Baseline (0 weeks) and after intervention (16 weeks) | The Quality of life will be assessed using a 32-item questionnaire |
| Sleep characteristics | Baseline (0 weeks) and after intervention (16 weeks) | Sleep characteristics will be assessed using the 10-item Pittsburgh Sleep Quality Index |
| Fat mass | Baseline (0 weeks) and after intervention (16 weeks) | Body composition measured with whole body air-displacement by the BodPod |
| Fat free mass | Baseline (0 weeks) and after intervention (16 weeks) | Body composition measured with whole body air-displacement by the BodPod |
| Anthropometrics (1) | Baseline (0 weeks) and after intervention (16 weeks) | Weight |
| Anthropometrics (2) | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | BMI |
| Anthropometrics (3) | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Waist and hip circumference (ratio) |
| Structural brain status (1) | Baseline (0 weeks) and after intervention (16 weeks) | MRI MPRAGE |
| Structural brain status (2) | Baseline (0 weeks) and after intervention (16 weeks) | T2FLAIR |
| Structural brain status (3) | Baseline (0 weeks) and after intervention (16 weeks) | R2\* |
| Circulating markers for low-grade systemic inflammation | Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks) | Markers for low-grade systemic inflammation (IL-6, TNF-alpha) |
| Flow-Mediated Vasodilation (FMD) | Baseline (0 weeks) and after intervention (16 weeks) | Peripheral vascular function, endothelial function |
Countries
Netherlands
Outcome results
None listed