Effect of Nordic Berries on Cognitive Function, Cardiometabolic Risk Markers and Gut Microbiota in Adults With Mild Cognitive Impairment (MINDBERRY)

A Randomized, Double-blind, Placebo-controlled Intervention Study to Evaluate the Effect of Nordic Berries on Cognitive Function, Cardiometabolic Risk Markers and Gut Microbiome in Adults With Mild Cognitive Impairment The MINDBERRY Trial

The aim of the current study is to investigate whether daily intake of Nordic berries for 12 weeks can improve cognitive abilities of adults with mild cognitive impairment, and whether the effect can be linked to changes in metabolic parameters.

Study Overview

• Status: Completed
• Conditions: Memory Impairment; Cognitive Impairment, Mild
• Intervention / Treatment: Other: Active berry product; Other: Reference product

Detailed Description

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 12 weeks 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 50 volunteers, are studied. Volunteers will be patients attending the Cognitive medicine unit at Ängelholm hospital, who have mild cognitive impairment (but not dementia). 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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Ängelholm, Sweden, 26253
    • Cognitve medicine
  • Ängelholm, Sweden
    • Cognitive medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age of 55 years or older.
2. Cognitive impairment in accordance with the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria and global deterioration scale (GDS) stage 3.
3. Capable and willing to give written informed consent.
4. Capable and willing to perform cognitive testing (mastering the Swedish language, functional vision and hearing or the use of visual or hearing aids during testing).
5. Capable and willing to ingest the study beverage for 12 weeks and to follow the instructions given.

Exclusion Criteria:

1. MMSE (Mini-Mental State Examination) <24 (at screening or in the last 3 months).
2. Cognitive disease (e.g. dementia) according to Global Deterioration Scale (GDS) stage 4 and up.
3. Severe affective disorder with current symptoms
4. Severe mental disorder.
5. Newly diagnosed or poorly regulated thyroid disease (unstable dose since 3 months back).
6. Ongoing insulin therapy.
7. Ongoing treatment for malignancy*.
8. 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).
9. Planned major intervention in health care over the next 3 months (the study period).
10. Undergoing antibiotic therapy for the last 3 months prior to inclusion in the study.
11. Allergy / intolerance to berries or other ingredients in the study products (i.e., colorants, aromas, starch).
12. Vegetarians / vegans.
13. Smoking.
14. Abuse of alcohol or psychoactive substance.
15. Significant change in medication over the last 3 months.
16. Daily, regular high consumption of berries or juices / marmalade / product with high content of these berries (guideline no more than 5 grams per day). (Can be recruited for the study if this intake ceases before visit 1. High consumes (approximately 1 dl of berries per day) has to cease with this at least one month before visit 1.)
17. Taking supplements with potential cognitive effects (e.g. omega-3, ginko biloba), or containing grape and berry extracts or probiotics (capsules or other). (Can be recruited if this intake ceases at least one month before visit 1).
18. Planned longer absence/vacation during the next 3 months (the study period).
19. Concurrent participation in other clinical intervention trials (dietary/pharmacological).

20. Other reasons that make the Study investigator in consultation with the responsible physician deem the person inappropriate to include.

    • basalioma exempt from exclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active berry product; Once daily consumption over the period of the study	Other: Active berry product; Subjects should consume the active product containing nordic berries daily during the 12 week intervention period.
Placebo Comparator: Reference product; Once daily consumption over the period of the study	Other: Reference product; Subjects should consume a reference product (isocaloric to active product) daily during the 12 week intervention period.; Other Names: inactive control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CANTAB - Paired Associate Learning test (PAL28)	To investigate how daily berry intake affects cognitive function (primary objective) measured by episodic memory	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting insulin		12 weeks
Episodic memory (test verbal recognition memory (VRM) (free-, immediate- and delayed recall)		12 weeks
Attention, psychomotor speed and executive function (Trail making test (TMT) A and B)		12 weeks
Selective attention and processing speed (Stroop color-word test)		12 weeks
Verbal fluency (letter "S" word fluency test)	Number of novel words on letter "S" during 60 seconds.	12 weeks
Behavior and quality of life (AES, Apathy evaluation score (self))	Answers given by the participants on 18 questions reflect apathy including behavioral, cognitive and emotional indicators on a scale 18-72 where higher scores reflect more apathy.	12 weeks
Behavior and quality of life (Apathy evaluation score (informant))	Answers given by someone close to the participant on 18 questions reflect apathy including behavioral, cognitive and emotional indicators on a scale 18-72 where higher scores reflect more apathy.	12 weeks
EuroQol five dimension (EQ-5D) life quality score.	Participant marks on a visual analogue scale from 0 to 100 how they value their current health status where 0 represents the lowest, and 100 highest, health status and quality of life.	12 weeks
Hospital Anxiety Depression (HAD) Score.	Self-assessment with 14 items that assess anxiety and depression symptoms before and after the intervention on a scale from 0 to 21, with higher scores indication the presence of symptoms.	12 weeks
Systolic blood pressure	Change in systolic blood pressure in mm/Hg	12 weeks
Diastolic blood pressure	Change in diastolic blood pressure in mm/Hg	12 weeks
Heart rate	Change in bpm (beats per minute)	12 weeks
Body weight	Change in body weight (kg)	12 weeks
BMI	Change in body weight index (kg/m^2)	12 weeks
Body fat composition	Body fat composition (% body fat, fat free mass (kg), basal metabolic rate (BMR) measured with TANITA scale.	12 weeks
Waist-to-hip ratio	Waist circumference/hip circumference	12 weeks
Fasting glucose (mM)		12 weeks
HOMA-IR	Homeostasis model assessment of insulin resistance (HOMA-IR)	12 weeks
Lipid metabolism: total cholesterol mg/dl		12 weeks
Lipid metabolism: LDL-cholesterol mg/dl		12 weeks
Lipid metabolism: HDL-cholesterol mg/dl		12 weeks
Lipid metabolism: triglycerides mg/dl		12 weeks
Lipid metabolism: apolipoprotein B/ apolipoprotein A1 ratio		12 weeks
Lipid metabolism: oxLDL	Oxidized LDL-cholesterol	12 weeks
Liver function: alanine aminotransferase (ALAT) (ukat/L)		12 weeks
Inflammation: hsCRP (mg/L)	high sensitive c-reactive protein	12 weeks
Inflammation: plasma serum amyloid A (mg/L)		12 weeks
Inflammation: IL-6 ng/L		12 weeks
Inflammation: TNFalfa ng/L		12 weeks
Inflammation: IL-12 ng/L		12 weeks
Inflammation: IL-15 ng/L		12 weeks
Inflammation: MCP-1 ng/L		12 weeks
Inflammation: sVCAM-1 (ukat/L)		12 weeks
Inflammation: IFN-g		12 weeks
Biomarker related to cognitive function: BDNF	Change in plasma brain-derived neurotrophic factor (BDNF)	12 weeks
PAL scores (PALTEA)	Change in PALTEA score at different levels of the test	12 weeks
VRM scores	Change in VRM scores at different levels of the test	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota composition	Change in 16s microbial composition in feces samples	12 weeks
Gut function	Questionnaire describing gut function and habits to be filled out before and after the intervention.	12 weeks
Exploratory: correlations between primary variables (cognitive function) and secondary outcome measures and gut microbiota composition.		12 weeks
Exploratory: analyses of interactions between effects on cognitive function and the participant characteristics; dietary habits, drugs, dementia risk-allele, education level and gender.		12 weeks
Adverse events	safety outcomes	12 weeks

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: Lund University; Berry Lab

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Actual): February 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 23, 2020

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: Mindberry2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No