About this trial
Impaired brain vascular function precedes the development of reduced cognitive performance, while brain insulin-resistance is associated with cognitive decline. Evidence from epidemiological studies has already suggested beneficial effects of wild blueberry consumption on cognitive performance. However, underlying mechanisms have not yet been established, while well-controlled trials on longer-term effects of wild blueberries on cognitive performance are highly needed. This study hypothesizes that longer-term wild blueberry intake improves (regional) brain vascular function and insulin-sensitivity, thereby improving cognitive performance in older men and women. The primary objectives are to investigate in older adults the effect wild blueberry consumption on (regional) vascular function and insulin-sensitivity in the brain, and to focus on changes in cognitive performance as assessed with the CANTAB neuropsychological test battery (i.e., secondary objective). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be non-invasively quantified by the non-invasive gold standard magnetic resonance imaging (MRI)- perfusion method Arterial Spin Labeling (ASL).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Men and women, aged between 60-75 years
BMI between 25-35 kg/m2 (overweight or obese)
Fasting plasma glucose < 7.0 mmol/L
Fasting serum total cholesterol < 8.0 mmol/L
Disqualifiers
Allergy or intolerance to berries
Left-handedness
Current smoker, or smoking cessation < 12 months
Diabetic patients
Trial design
Crossover
Treatments tested in this trial
Wild blueberry powder
Dietary supplementStudy volunteers will consume daily 26 grams of wild blueberry powder for 16 weeks, which has to be dissolved in a glass of water.
Treatment groups
Trial outcomes
Primary outcomes
MRI-brain perfusion measurement Arterial Spin Labeling
Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin (brain insulin-sensitivity) will be non-invasively quantified by MRI-perfusion method Arterial Spin Labeling (ASL).
Secondary outcomes
Cognitive performance measurement by Cambridge Neuropsychological Test Automated Battery
Cognitive performance will be investigated using Cambridge Neuropsychological Test Automated Battery (CANTAB), which will be performed on an Ipad. The cognitive task performance will be tested in three important cognitive domains namely attention, memory and executive function. Learning effects are prevented by randomization of the intervention periods and the settings of CANTAB, including parallel modes and stimuli randomization. The test will be performed in Dutch.
Brain Insulin Sensitivity
Change in cerebral blood flow, as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL), before and after application of intranasal insulin (160 IU).
Other outcomes
Assessment of Glucose Metabolism by 7-Point OGTT
Glucose metabolism will be evaluated using a 7-point oral glucose tolerance test (OGTT). In this test, a participant drinks a glucose-containing solution, and blood samples are collected at seven time points (0', 15', 30', 45', 60', 90', 120') over two hours. Measuring glucose levels at seven different points provides a detailed picture of how the body processes and clears sugar from the blood, helping to identify early changes in insulin sensitivity and overall metabolic health.
Assessment of cardiovascular function by Flow-Mediated Vasodilation (FMD)
Vascular health will be assessed by flow-mediated vasodilation (FMD, expressed as %), a non-invasive ultrasound technique that measures how well a blood vessel widens in response to increased blood flow. By briefly restricting blood flow in the arm (by means of a cuff on the fore arm) and then releasing it, investigators can see how effectively the brachial artery relaxes and dilates. This response reflects the function of the endothelium, the inner lining of blood vessels, and is considered an important indicator of cardiovascular health. The percentage indicates the relative increase in the brachial diameter compared to its baseline size.
Assessment of cardiovascular function by Carotid Artery Reactivity (CAR)
The peripheral vascular function will be assessed by the carotid artery reactivity (CAR, expressed as %), a non-invasive technique that evaluates the ability of the carotid artery to dilate or constrict in response to specific physiological or pharmacological stimuli. The percentage indicates the relative change in the carotid artery's diameter compared to its baseline size. This method provides insight into endothelial function, vascular smooth muscle responsiveness, and overall arterial health, serving as an early marker for cardiovascular risk.
Assessment of Arterial Stiffness by Pulse Wave Analysis (PWA)
Arterial stiffness and central blood pressure will be assessed by pulse wave analysis (PWA). This non-invasive method records the shape of the pulse wave generated by each heartbeat, from the wrist or arm. From this signal, central blood pressure is expressed in millimeters of mercury (mmHg), while derived indices of arterial stiffness (such as the augmentation index, AIx) are expressed in percentages (%), representing the relative contribution of reflected waves to the overall pulse wave. By analyzing how the wave travels and reflects in the arteries, investigators can gain insight into arterial elasticity, vascular resistance, and the overall condition of the cardiovascular system.
Sponsors and contacts
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Maastricht University Medical Center
Lead sponsor
Wild Blueberry Association of North America
Collaborator