A double-blind, randomised, controlled, parallel arm chronic intervention trial with healthy older adults will be conducted to determine the effect of a flavonoid-rich supplement on cognitive function, peripheral arterial health and brain mechanisms. It is predicted that chronic flavonoid supplementation will result in cognitive benefits and that these may be due to beneficial effects of flavonoids on vascular and brain function.

There has recently been an increasing interest in the potential of flavonoids, plant derived compounds found in foods such as fruit and vegetables, to improve cognitive function. Research suggests that flavonoids improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects, for example by increasing cerebral blood flow (CBF), protecting vulnerable neurons, or by stimulating neuronal function and growth. The proposed research will involve a parallel design chronic dietary supplementation trial using a flavonoid-supplement and a matched control containing no flavonoids, to investigate long-term changes in cognitive performance. To understand the neural mechanisms behind potential changes in cognitive performance, resting cerebral blood flow (CBF), blood-oxygen level dependent (BOLD) response during two sensitive tests of cognitive performance, and structural brain changes will be measured in a group of healthy elderly adults (N=70, age range 60-75 years) using magnetic resonance imaging (MRI). Additionally, peripheral vascular health will be measured using flow mediated dilatation (FMD), and bioavailability of flavonoid monomers and metabolites will be determined through analysis of plasma and urine samples. Biomarkers in the blood associated with vascular health and neural functioning as well as markers of interest in relation to the possible mechanisms of action of flavonoids will also be measured. All endpoints will be acquired before and after a 24-week chronic supplementation of either a high flavonoid supplementation or a control product, consumed in addition to participants' normal diet. Measures will also be taken following a 12-week post-intervention washout period in order to investigate whether any beneficial effects are sustained following cessation of supplementation.

INCLUSION CRITERIA:

• Males and females aged 60-75 years

• English as primary language, able to understand the study information sheet, follow instructions in English and give informed consent

• Non-smokers

• Alcohol consumption should be within the current National Health Service (NHS) recommendation - women: ≤21 units per week (max 3 per day), 1 large 250mL glass of wine (Alcohol By Volume 12%) is 3 units; men: ≤ 28 units per week (max 4 per day), 1 pint of strong lager/beer/cider (Alcohol By Volume 5.2%) is 3 units

• BP <150/90 (determined at screening)

• BMI <30 (determined at screening)

• Full blood count parameters within the normal range, specifically:

  • Haemoglobin to check for anaemia (>12.5 g/dL for males and >11.5 g/dL for females)

  • Total white cell count (3.6-11.0 x109/L)

  • Differential count:

    • Neutrophils (1.8 - 7.5 x109/L)
    • Lymphocytes (1.0 - 4.0 x109/L)
    • Monocytes (0.2 - 0.8 x109/L)
    • Eosinophils (0.1 - 0.4 x109/L)
    • Basophils (0.02 - 0.1 x109/L)

  • Normal platelet function (platelet count 140-400 x109/L)

  • Red cell count (4.50-6.50 x1012/L for males; 3.80-5.80 x1012/L for females)

  • Haematocrit (0.40-0.54 L/L for males; 0.37-0.47 L/L for females)

  • Mean Cell Volume (80-100 fL)

  • Mean Cell Haemoglobin (27-32 pg)

  • Reticulocyte Count (0.2-2.0 %)

• The following blood parameters within the normal range:

  • Liver function (gamma-glutamyl transpeptidase [GGT] level < 80 IU/L, alanine transaminase [ALT] < 30 U/L, alkaline phosphatase [ALP] < 320 U/L),
  • Kidney function (total bilirubin ≤ 22 μmol/L, creatinine ≤ 106 μmol/L, uric acid < 506 μmol/L),
  • Fasting blood glucose level (< 7 mmol/L),
  • Triglycerides (< 2.2 mmol/L)
  • Plasma cholesterol (< 8 mmol/L)

EXCLUSION CRITERIA:

• General global cognitive impairment (Mini Mental State Examination score < 24)

• Un-corrected vision or hearing problems

• Speech or communication difficulties

• Currently suffering from depression (Brief Symptom Inventory score of ≥ 11)

• Diagnosed with any learning difficulty such as Dyslexia or Dyspraxia

• Sensitive/allergic to the intervention or any of the study foods

• Suffering from any form of clinically diagnosed disease, including:

  • Major mental illness (current or previous episode with hospitalization)
  • Chronic fatigue syndrome
  • Liver disease
  • Diabetes mellitus
  • Heart disease or myocardial infarction

• Taking blood pressure medication, anticoagulants, anti-platelet medication or antidepressants

• On a weight reducing dietary regimen or taking any dietary supplements (including dietary fatty acids), unless willing to temporarily refrain from taking dietary supplements for the duration of the study

• Subjects consuming more than seven portions of fruit and vegetables a day

• Subjects consuming more than five cups of tea a day

• Men taking part in more than 10.5 hours of moderate to vigorous exercise per week and women taking part in more than 7 hours of moderate to vigorous exercise per week (assessed on an individual basis to avoid recruitment of people who exercise too vigorously)

• Taking illegal substances

MRI part:

• Has a heart pacemaker or metal implants (including any non-removable ferro-magnetic dental items)
• Any body piercing items that cannot be removed
• Is claustrophobic

Note: Participation in other research trials within the last month will need to be declared and may affect the start date for participation in the current trial.

To achieve the aim of data sharing with the wider community data will be submitted for inclusion in the Biotechnology and Biological Sciences Research Council (BBSRC)-funded Code Analysis, Repository & Modelling for E-Neuroscience (CARMEN) depository for neurophysiological datasets (http://www.carmen.org.uk). Data will also be accessible by making a direct request to the PI, and will be transferred to the recipient. Publications will be in open access journals where possible. If not possible, due to the need to reach the widest possible audience, pre-publication manuscripts arising from the project will be deposited in the free and publicly searchable University of Reading research database (CentAUR: http://centaur.reading.ac.uk). All data will be made available in an anonymised format upon request following publication of main findings. It is envisaged that the entire datasets will be available 6 months following the end of the project and maintained for a period of at least 10 years.