Study on the Chronic and Acute Effects of Nordic Berry Beverage on Cognitive Function

Study Overview
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Brief Summary
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The aim of the current study is to investigate whether acute and 12-weeks daily intake of Nordic berries can improve cognitive abilities of adults without cognitive disease, and whether the effect can be linked to changes in metabolic parameters.

Detailed Description
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The study will be conducted with a randomized, double-blind, parallel-group (2 arms) placebo-controlled, single-center interventional design. The aim is to investigate the effects on cognitive function and cardiometabolic risk markers after acute and 12 weeks daily intake of a berry product vs. a reference product. The reference will be isocaloric and matched in taste, appearance, volume and macronutrient composition to the active berry product. Two groups, each of 30 volunteers, are studied. One group of volunteers will consume the berry product while the other group act as control and will consume the reference product. Each volunteer will be seen for a screening visit as well as one pre- and one post-intervention visit at the clinic. In addition, there will be 2 follow-up calls in between visits. Pre- and post intervention visits will include cognitive assessment with the CANTAB battery (episodic memory and verbal recognition memory), as well as additional cognitive and behavioral tests. Cardiometabolic parameters will be addressed (plasma glucose, insulin, inflammatory markers, blood lipids, body composition) and fecal samples collected.

Official Title
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Study on the Chronic and Acute Effects of Nordic Berry Beverage on Cognitive Function, Cardiometabolic Risk Markers and Gut Microbiome: A Randomized, Double-blind, Placebo-controlled Intervention

Conditions
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Age-related Cognitive Decline

Intervention / Treatment
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* Other: Active berry product
* Other: Reference berry-like product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60-85 years. Capable and willing to give written informed consent. Capable and willing to perform cognitive testing in Swedish (mastering the Swedish language, functional vision and hearing or the use of visual or hearing aids during testing). Capable and willing to ingest the study beverage for 12 weeks and to follow the instructions given. Agree to maintain consistent dietary habits and physical activity levels for the duration of the study Exclusion Criteria: Known to be affected by major neurocognitive disorder/dementia or low score on cognitive screening test (Mini Mental State Examination (MMSE) score less than 24. Affected by other medical condition(s) or medication(s) known to significantly affect cognitive function. Past history of brain damage, significant head trauma (including loss of consciousness as a result), brain surgery or stroke. Underweight (BMI <18.5). Significant psychiatric disorders with current symptoms. Type 1 diabetes, recently diagnosis of Type 2 diabetes (<12 months) or ongoing insulin treatment. Ongoing treatment for malignancy*. Significant change in medication over the last 3 months. Undergoing antibiotic therapy for the last 3 months prior to inclusion in the study. Blood donation before (3 months) or during the study period. Planned major intervention in health care or change in medication over the next 3 months (study period). Currently active smoker or regular use of other nicotine products. Drug or alcohol abuse. Conditions with major impact on the gastrointestinal tract (such as Crohn's disease, ulcerative colitis, diagnosed gluten intolerance, undertaken intestinal resection or weight loss surgery). Allergy / intolerance to berries or other ingredients in the study products (i.e., colorants, aromas, starch). Vegetarians / vegans. Daily, regular high consumption (approximately 1 dl or more per day) of berries or juices / marmalade / products with high content of bilberries and lingonberries. (Can be recruited if consumption has ceased to less than 5 grams of berries per day at least 1 month before visit 1.). Taking supplements with potential cognitive effects (e.g., omega-3, ginko biloba, Souvenaid), or containing grape and berry extracts or probiotics (capsules or ProViva). (Can be recruited if this intake ceases at least one month before visit 1). Planned longer absence/vacation during the next 3 months (study period). Sharing household with someone participating in the current study Concurrent participation in other clinical intervention trials (dietary/pharmacological). Other reasons that make the SD in consultation with the PI deem the person inappropriate to include. *basalioma exempt from exclusion criteria

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active berry product<br>Once daily consumption over the period of the study | Other: Active berry product<br>* Subjects should consume the active product containing nordic berries daily during the 12 week intervention period.<br>|
| Placebo Comparator: Reference berry-like product<br>Once daily consumption over the period of the study | Other: Reference berry-like product<br>* Subjects should consume a reference product (isocaloric to active product, containing berry aromas and colouring but no actual berry compounds) daily during the 12 week intervention period.<br>* Other names: Inactive control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive measures-memory | Episodic memory - assessed using computerized cognitive battery including PAL (paired associates learning) test. | Change from baseline following 12 weeks daily consumption, compared to control | 
| Cognitive measures-memory | Episodic memory - assessed using computerized cognitive battery including VRM (verbal recognition memory) test | Change from baseline following 12 weeks daily consumption, compared to control | 
| Cognitive measures - memory | Working memory - assessed using computerized cognitive battery including SWM (spatial working memory) test. | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cognitive measures - memory | Working memory - assessed using computerized cognitive battery including SDPT (symbol digits processing test). | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cognitive measures - executive function | Executive function - assessed using computerized cognitive battery including TMT (trail making test) A & B. | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cognitive measures - executive function | Executive function - assessed using computerized cognitive battery including PASAT (paced auditory serial addition test). | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cognitive measures - executive function | Executive function - assessed using computerized cognitive battery including Stroop test. | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cognitive measures - executive function | Executive function, verbal fluency - assessed using computerized cognitive battery including F-A-S test measuring word fluency | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cognitive measures - attention | Attention, reaction time - assessed using computerized cognitive battery including RTI (reaction time) test. | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cognitive measures | Global cognitive function - assessed by calculating a z-score from the cognitive battery score outcomes | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating plasma biomarkers relating to cognitive function | Brain derived neurotrophic factor (BDNF) | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Mood measurement | assessed using SCAS (the Swedish Core Affect Scale) mood questionnaire. A validated self-report measure of affective state. The SCAS comprises of 12 affective states that subjects rate on a scale from 1 - 10. | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Self-reported quality of life | assessed using the quality of life scale from the EQ-5D (EuroQol 5 Dimension) self-report survey. The subject grades their current overall quality of life on a scale 0-100. | Difference from baseline vs control following 12 weeks of daily consumption | 
| Well-being measurement | Assessed with World Health Organization- Five Well-Being Index (WHO-5). A validated 5 item scale for self-reporting levels of perceived well-being over the last two weeks. Items are rated using a 5-point scale. | Difference from baseline vs control following 12 weeks of daily consumption | 
| Subjective memory | Assessed using 3 simple questions about the subject's own memory evaluation. The subject is asked to rate their memory function (scale 0 to 7), how they percieve their own memory is working compared to others in the same age (0 to 5) and if anyone close to them has expressed concern over the subjects' memory | Difference from baseline vs control following 12 weeks of daily consumption | 
| Cardiometabolic risk factor | blood pressure (SBP) | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cardiometabolic risk factor | blood pressure (DBP) | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Cardiometabolic risk factor | Heart rate (HR) | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Body composition | Body weight (kg) | Change from baseline following 12 weeks daily consumption, compared to control | 
| Body composition | Body mass index (BMI) (e.g., weight (kg) and height (m) will be combined to report BMI in kg/m^2). | Change from baseline following 12 weeks daily consumption, compared to control | 
| Body composition | body fat % (measured by bioelectrical impedance analysis) | Change from baseline following 12 weeks daily consumption, compared to control | 
| Body composition | Waist circumference (cm) | Change from baseline following 12 weeks daily consumption, compared to control | 
| Biomarkers of glycemia | glucose levels in blood | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Biomarkers of glycemia | insulin levels in blood | Change from baseline at 1.5 hours post-dose, and 12 weeks daily consumption, compared to control | 
| Biomarkers of glycemia | HOMA-IR (insulin resistance index, calculated based on fasting glucose and insulin levels) | Change from baseline following 12 weeks daily consumption, compared to control | 
| Biomarkers of glycemia | Fructosamine levels in blood | Change from baseline following 12 weeks daily consumption, compared to control | 
| Biomarkers of lipemia in blood plasma | triacylglycerols | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarkers of lipemia in blood plasma | total cholesterol | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarkers of lipemia in blood plasma | HDL-cholesterol | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarkers of lipemia in blood plasma | LDL-cholesterol | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarkers of lipemia in blood plasma | ApoB/A1 | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarker endothelial function in blood plasma | sVCAM-1 | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarkers of liver function in blood plasma | ALAT | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarkers of inflammation and oxidative stress blood plasma | Interleukin | Difference from baseline vs control following 12 weeks of daily consumption | 
| Biomarkers of inflammation and oxidative stress blood plasma | acute phase proteins (C-reactive protein) | Difference from baseline vs control following 12 weeks of daily consumption | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognitive function, memory