Effects of Wild Blueberry Consumption on Brain Function in Elderly

NCT07177781 | Recruiting DMC

• 1 other identifier: METC 24-040
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Brain Insulin-sensitivity; Brain Vascular Function; Cerebral Blood Flow

Keywords

Cognitive performance; Brain insulin-resistance; Brain vascular function; Cerebral blood flow; Wild blueberry; Brain insulin-sensitivity; Anthocyanin

Outcome Measures

Primary Outcomes (1)

• 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).

  Change in brain perfusion at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.

Secondary Outcomes (2)

• Cognitive performance measurement by Cambridge Neuropsychological Test Automated Battery

  Change in cognitive performance at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.

• Brain Insulin Sensitivity

  Change in outcomes at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.

Other Outcomes (23)

• Assessment of Glucose Metabolism by 7-Point OGTT

  Change in glucose metabolism at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.

• Assessment of cardiovascular function by Flow-Mediated Vasodilation (FMD)

  Change in cardiovascular function at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.

• Assessment of cardiovascular function by Carotid Artery Reactivity (CAR)

  Change in peripheral vascular function at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.

Study Arms (2)

Matched placebo

NO INTERVENTION

Adults will receive in a random order, freeze-dried wild blueberry powder or a matched placebo for sixteen weeks, with a wash-out period of minimal eight weeks in-between. The placebo is an appearance, taste and macronutrient, fiber and vitamin C-matched powder containing blueberry flavoring and aroma, coloring, glucose, fructose, citric acid, ascorbic acid, cellulose, fibersol-2, xanthin gum, pectin, and silica. The placebo does not contain any form of anthocyanin that could potentially interfere with the wild blueberry intervention.

Wild blueberry powder (wild blueberry intervention)

EXPERIMENTAL

The wild blueberry intervention consist of 100% freeze-dried wild blueberry powder, containing anthocyanins. Participants will consume daily 26 grams of freeze-dried wild blueberry powders for 16 weeks. Participants should consume the powders by mixing them with water once daily in the morning

Dietary Supplement: Wild blueberry powder

Interventions

Wild blueberry powder DIETARY_SUPPLEMENT

Study volunteers will consume daily 26 grams of wild blueberry powder for 16 weeks, which has to be dissolved in a glass of water.

Wild blueberry powder (wild blueberry intervention)

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 evidences during the screening visit.

You may not qualify if:

• Allergy or intolerance to berries
• Left-handedness
• Current smoker, or smoking cessation \< 12 months
• Diabetic patients
• Familial hypercholesterolemia
• Abuse of drugs
• More than 3 alcoholic consumptions per day
• Use of products or dietary supplements known to interfere with the main 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 (e.g., pacemaker, surgical clips/material in body, metal splinter in eye, claustrophobia)

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Wild Blueberry Association of North America: collaborator

Study Sites (1)

Maastricht University, Departement of Nutrition and Movement Sciences

Maastricht, Limburg, 6200 MD, Netherlands

RECRUITING

Related Publications (27)

• Wolters FJ, Zonneveld HI, Hofman A, van der Lugt A, Koudstaal PJ, Vernooij MW, Ikram MA; Heart-Brain Connection Collaborative Research Group. Cerebral Perfusion and the Risk of Dementia: A Population-Based Study. Circulation. 2017 Aug 22;136(8):719-728. doi: 10.1161/CIRCULATIONAHA.117.027448. Epub 2017 Jun 6.

  PMID: 28588075 BACKGROUND

• Ahles S, Stevens YR, Joris PJ, Vauzour D, Adam J, de Groot E, Plat J. The Effect of Long-Term Aronia melanocarpa Extract Supplementation on Cognitive Performance, Mood, and Vascular Function: A Randomized Controlled Trial in Healthy, Middle-Aged Individuals. Nutrients. 2020 Aug 17;12(8):2475. doi: 10.3390/nu12082475.

  PMID: 32824483 BACKGROUND

• Ivanov D, Gardumi A, Haast RAM, Pfeuffer J, Poser BA, Uludag K. Comparison of 3T and 7T ASL techniques for concurrent functional perfusion and BOLD studies. Neuroimage. 2017 Aug 1;156:363-376. doi: 10.1016/j.neuroimage.2017.05.038. Epub 2017 May 19.

  PMID: 28528845 BACKGROUND

• Kullmann S, Veit R, Peter A, Pohmann R, Scheffler K, Haring HU, Fritsche A, Preissl H, Heni M. Dose-Dependent Effects of Intranasal Insulin on Resting-State Brain Activity. J Clin Endocrinol Metab. 2018 Jan 1;103(1):253-262. doi: 10.1210/jc.2017-01976.

  PMID: 29095982 BACKGROUND

• Alsop DC, Detre JA, Golay X, Gunther M, Hendrikse J, Hernandez-Garcia L, Lu H, MacIntosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2015 Jan;73(1):102-16. doi: 10.1002/mrm.25197. Epub 2014 Apr 8.

  PMID: 24715426 BACKGROUND

• Azari H, Morovati A, Pourghassem Gargari B, Sarbakhsh P. Beneficial effects of blueberry supplementation on the components of metabolic syndrome: a systematic review and meta-analysis. Food Funct. 2022 May 10;13(9):4875-4900. doi: 10.1039/d1fo03715c.

  PMID: 35445669 BACKGROUND

• Joris PJ, Plat J, Bakker SJ, Mensink RP. Long-term magnesium supplementation improves arterial stiffness in overweight and obese adults: results of a randomized, double-blind, placebo-controlled intervention trial. Am J Clin Nutr. 2016 May;103(5):1260-6. doi: 10.3945/ajcn.116.131466. Epub 2016 Apr 6.

  PMID: 27053384 BACKGROUND

• Joris PJ, Plat J, Kusters YH, Houben AJ, Stehouwer CD, Schalkwijk CG, Mensink RP. Diet-induced weight loss improves not only cardiometabolic risk markers but also markers of vascular function: a randomized controlled trial in abdominally obese men. Am J Clin Nutr. 2017 Jan;105(1):23-31. doi: 10.3945/ajcn.116.143552. Epub 2016 Nov 23.

  PMID: 27881395 BACKGROUND

• Nijssen KMR, Mensink RP, Plat J, Joris PJ. Longer-term mixed nut consumption improves brain vascular function and memory: A randomized, controlled crossover trial in older adults. Clin Nutr. 2023 Jul;42(7):1067-1075. doi: 10.1016/j.clnu.2023.05.025. Epub 2023 Jun 3.

  PMID: 37296019 BACKGROUND

• Tischmann L, Adam TC, Mensink RP, Joris PJ. Longer-term soy nut consumption improves vascular function and cardiometabolic risk markers in older adults: Results of a randomized, controlled cross-over trial. Clin Nutr. 2022 May;41(5):1052-1058. doi: 10.1016/j.clnu.2022.03.014. Epub 2022 Mar 14.

  PMID: 35395555 BACKGROUND

• 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.

  PMID: 38128733 BACKGROUND

• Kleinloog JPD, Mensink RP, Smeets ETHC, Ivanov D, Joris PJ. Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men. Neuroimage Clin. 2022;35:103115. doi: 10.1016/j.nicl.2022.103115. Epub 2022 Jul 14.

  PMID: 35843050 BACKGROUND

• Nijssen KMR, Mensink RP, Joris PJ. Effects of Intranasal Insulin Administration on Cerebral Blood Flow and Cognitive Performance in Adults: A Systematic Review of Randomized, Placebo-Controlled Intervention Studies. Neuroendocrinology. 2023;113(1):1-13. doi: 10.1159/000526717. Epub 2022 Aug 24.

  PMID: 36219990 BACKGROUND

• Kleinloog JPD, Tischmann L, Mensink RP, Adam TC, Joris PJ. Longer-term soy nut consumption improves cerebral blood flow and psychomotor speed: results of a randomized, controlled crossover trial in older men and women. Am J Clin Nutr. 2021 Dec 1;114(6):2097-2106. doi: 10.1093/ajcn/nqab289.

  PMID: 34510189 BACKGROUND

• Rees A, Dodd GF, Spencer JPE. The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function. Nutrients. 2018 Dec 1;10(12):1852. doi: 10.3390/nu10121852.

  PMID: 30513729 BACKGROUND

• Wood E, Hein S, Mesnage R, Fernandes F, Abhayaratne N, Xu Y, Zhang Z, Bell L, Williams C, Rodriguez-Mateos A. Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial. Am J Clin Nutr. 2023 Jun;117(6):1306-1319. doi: 10.1016/j.ajcnut.2023.03.017. Epub 2023 Mar 25.

  PMID: 36972800 BACKGROUND

• Ahles S, Joris PJ, Plat J. Effects of Berry Anthocyanins on Cognitive Performance, Vascular Function and Cardiometabolic Risk Markers: A Systematic Review of Randomized Placebo-Controlled Intervention Studies in Humans. Int J Mol Sci. 2021 Jun 17;22(12):6482. doi: 10.3390/ijms22126482.

  PMID: 34204250 BACKGROUND

• Snyder HM, Corriveau RA, Craft S, Faber JE, Greenberg SM, Knopman D, Lamb BT, Montine TJ, Nedergaard M, Schaffer CB, Schneider JA, Wellington C, Wilcock DM, Zipfel GJ, Zlokovic B, Bain LJ, Bosetti F, Galis ZS, Koroshetz W, Carrillo MC. Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. Alzheimers Dement. 2015 Jun;11(6):710-7. doi: 10.1016/j.jalz.2014.10.008. Epub 2014 Dec 12.

  PMID: 25510382 BACKGROUND

• Joris PJ, Mensink RP, Adam TC, Liu TT. Cerebral Blood Flow Measurements in Adults: A Review on the Effects of Dietary Factors and Exercise. Nutrients. 2018 Apr 25;10(5):530. doi: 10.3390/nu10050530.

  PMID: 29693564 BACKGROUND

• Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S. Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol. 2011 Jan;68(1):51-7. doi: 10.1001/archneurol.2010.225. Epub 2010 Sep 13.

  PMID: 20837822 BACKGROUND

• Kullmann S, Heni M, Hallschmid M, Fritsche A, Preissl H, Haring HU. Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans. Physiol Rev. 2016 Oct;96(4):1169-209. doi: 10.1152/physrev.00032.2015. Epub 2016 Aug 3.

  PMID: 27489306 BACKGROUND

• Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol. 2009 Mar;66(3):300-5. doi: 10.1001/archneurol.2009.27.

  PMID: 19273747 BACKGROUND

• Neergaard JS, Dragsbaek K, Christiansen C, Nielsen HB, Brix S, Karsdal MA, Henriksen K. Metabolic Syndrome, Insulin Resistance, and Cognitive Dysfunction: Does Your Metabolic Profile Affect Your Brain? Diabetes. 2017 Jul;66(7):1957-1963. doi: 10.2337/db16-1444. Epub 2017 Apr 7.

  PMID: 28389469 BACKGROUND

• van der Flier WM, Skoog I, Schneider JA, Pantoni L, Mok V, Chen CLH, Scheltens P. Vascular cognitive impairment. Nat Rev Dis Primers. 2018 Feb 15;4:18003. doi: 10.1038/nrdp.2018.3.

  PMID: 29446769 BACKGROUND

• Biessels GJ, Deary IJ, Ryan CM. Cognition and diabetes: a lifespan perspective. Lancet Neurol. 2008 Feb;7(2):184-90. doi: 10.1016/S1474-4422(08)70021-8.

  PMID: 18207116 BACKGROUND

• Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Sep;42(9):2672-713. doi: 10.1161/STR.0b013e3182299496. Epub 2011 Jul 21.

  PMID: 21778438 BACKGROUND

• Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang HY, Ahima RS, Craft S, Gandy S, Buettner C, Stoeckel LE, Holtzman DM, Nathan DM. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol. 2018 Mar;14(3):168-181. doi: 10.1038/nrneurol.2017.185. Epub 2018 Jan 29.

  PMID: 29377010 BACKGROUND

Central Study Contacts

Peter P.J. Joris, PhD

CONTACT

0031883887250; p.joris@maastrichtuniversity.nl

Tineke Degens, MSc

CONTACT

0031433883547; tineke.degens@maastrichtuniversity.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, controlled cross-over design. Participants will receive, in a random order, daily 26 grams of wild blueberry powder or a matched placebo for sixteen weeks, separated by a washout period of at least 8 weeks.

Study Record Dates

• First Submitted: November 12, 2024
• First Posted: September 17, 2025
• Study Start: December 5, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: September 17, 2025

Record last verified: 2024-11

Locations

NL (1)