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| Name | Class |
|---|---|
| The International Nut and Dried Fruit Council (INC) | UNKNOWN |
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Impaired brain vascular function precedes the development of reduced cognitive performance, while brain insulin-resistance is also associated with cognitive decline. The Mediterranean diet, which is rich in nuts, may protect against the development of impaired cognitive performance. The hypothesis is that long-term mixed nut consumption increases brain insulin-sensitivity thereby improving brain vascular function and cognitive performance. The primary objective is to evaluate in elderly men and women the effect of 16-week mixed nut consumption on cerebral blood flow, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labelling (ASL). Cerebral blood flow is a robust and sensitive physiological marker of brain vascular function. Secondary objectives are to investigate effects on the cerebral blood flow response to intranasal insulin delivery - a marker of insulin-sensitivity in the human brain - as quantified by ASL, and cognitive functioning as assessed with a neuropsychological test battery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental | Experimental | Mixed nuts |
|
| Control | No Intervention | No mixed nuts |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mixed Nuts | Dietary Supplement | Study volunteers will receive daily 60 g of mixed nuts (15 g walnut, 15 g cashew, 15 g hazelnut, 15 g pistachio) for 16 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Brain Vascular Function | Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Cognitive performance |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose metabolism | Oral Glucose Tolerance Test (OGTT) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Peripheral vascular function (1) | Flow-mediated vasodilation (FMD) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter J Joris, PhD | Maastricht University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University Medical Center | Maastricht | Limburg | 6229 ER | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38128733 | Derived | Nijssen KM, Mensink RP, Plat J, Ivanov D, Preissl H, Joris PJ. Mixed nut consumption improves brain insulin sensitivity: a randomized, single-blinded, controlled, crossover trial in older adults with overweight or obesity. Am J Clin Nutr. 2024 Feb;119(2):314-323. doi: 10.1016/j.ajcnut.2023.12.010. Epub 2023 Dec 20. |
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Crossover Assignment Participants will receive, in random order, daily 60 g of mixed nuts (mixed nut treatment) or no food products (control treatment) for sixteen weeks, separated by a washout period of at least 8 weeks.
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Cambridge Neuropsychological Test Automated Battery (CANTAB) |
| Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Peripheral vascular function (2) | Carotid artery reactivity (CAR) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Peripheral vascular function (3) | Pulse wave analysis (PWA) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Peripheral vascular function (4) | Pulse wave velocity (PWV) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Peripheral vascular function (5) | Retinal microvascular calibers | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Blood pressure | Office and 24-hour ambulatory blood pressure | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Advanced glycation endproducts | Serum protein-bound advanced glycation endproducts (AGEs) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Blood lipids | Lipids and Lipoproteins | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Blood glucose | Glucose | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Blood insulin | Insulin | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Blood markers for low-grade systemic inflammation | Markers for low-grade systemic inflammation (IL-6, TNF-alpha) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Blood markers for microvascular function | Markers for microvascular function (sCAM-1, vWf, cGMP) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Blood marker of neurogenesis | Brain-derived neurotrophic factor | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Parameters for compliance | Alpha-linoleic acid levels (blood) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Structural brain status | MRI Structural MPRAGE scan | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Functional connectivity | Resting and task-induced blood-oxygen-level-dependent (BOLD) response, as quantified by functional MRI T2*-weighted imaging. | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Fat distribution in abdomen | Magnetic Resonance Imaging measurements will be included to quantify abdominal fat compartments (i.e. subcutaneous and visceral fat) and fat content of abdominal organs (i.e. liver and pancreas). | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Microbiota composition | Fecal samples will be collected to be used for analysing different species of microbiota. | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Other perceivable benefits: Quality of Life | The Quality of life will be assessed using a 32-item questionnaire | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Other perceivable benefits: Sleep characteristics | Sleep characteristics will be assessed using the 10-item Pittsburgh Sleep Quality Index | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Other perceivable benefits: Mood | Mood will be tested using the Affect Grid | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Other perceivable benefits: Physical fitness (1) | Timed up-and-go test (TUGT) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Other perceivable benefits: Physical fitness (2) | The 6-minute walk test (6 MWT) | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Other perceivable benefits: Physical fitness (3) | Handgrip test | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Other perceivable benefits: Physical fitness (4) | Muscle strength test, as measured using the Biodex system | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Weight | Weight in kilograms | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Length | Length in meters | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Waist circumference | Waist circumference in centimeters | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Hip circumference | Hip circumference in centimeters | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Indirect fat distribution | Measured by skinfold measurements | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |
| Food intake | Food intake will be assessed using the Food Frequency Questionnaire | Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period. |