Tremendous progress has been made in characterizing the interactions between the central nervous system and the gastrointestinal tract. This concept of a gut-brain axis suggests that influencing bacteria in the gut is a promising approach for developing new ways of benefiting brain function. This is particularly relevant for an ageing population for which cognitive decline is a common symptom and can be an indicator for the development of neurodegenerative conditions such as dementia. There is good evidence already that nutrition can delay the development of cognitive decline in ageing, in particular for ageing-sensitive brain regions such as the medial temporal lobe, however this has been little explored for cranberry intake. Cranberries are high in plant-derived nutrients called polyphenols, which have been suggested to promote brain function and protect against disease-causing mechanisms. In the proposed project we will pioneer work to investigate the impact of cranberry intake on gut bacteria and how it relates to cognitive performance in ageing and associated regions in the brain.

This study is being conducted by Chief Investigators Dr David Vauzour and Prof Michael Hornberger at the University of East Anglia. Sixty participants (i.e. n=30 control and treatment groups) aged 50-80 years old, with no memory complaints will be recruited for this 12-week double-blind placebo-controlled parallel intervention of cranberry flavonoids. Freeze-dried cranberry or a matched placebo will be taken twice daily for the duration of the trial. Blood, urine and faecal samples will be collected for microbiome, DNA, biochemical and nutritional analysis. Participants will also undergo cognitive testing, as well as MRI scanning to detect changes in brain physiology.

Inclusion Criteria:

• Aged between 50 and 80 years old.
• Willing and able to provide written informed consent.
• Fluent in written and spoken English.
• Normal or corrected to normal vision and hearing.
• Understands and is willing and able to comply with all study procedures.

Exclusion Criteria:

• Diagnosis of any form of dementia or significant neurological condition.
• Significant memory complaints.
• Past history or MRI evidence of brain damage, including significant trauma, stroke, learning difficulties or serious neurological disorder, including a loss of consciousness for more than 24 hours.
• Currently smoking or ceased smoking less than 6 months ago.
• Chronic fatigue syndrome, liver disease, diabetes mellitus, or gall bladder abnormalities.
• History of alcohol or drug dependency.
• Clinically diagnosed psychiatric disorder.
• Existing diagnosed gastrointestinal disorders likely to impact on absorption of flavonoids.
• Known allergy to the intervention supplement.
• Any significant medical condition likely to affect participation.
• Currently a participant or have been a participant in any other study involving an investigational product within the last 4 weeks.
• Uncontrolled hypertension (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg).
• Major cardiovascular event, such as myocardial infarction, within the last 12 months.
• On a stable prescription of blood pressure lowering medication or non-steroidal anti-inflammatory drugs. for fewer than 2 months.
• Prescribed anti-coagulant/blood thinning medication (eg. warfarin).
• Taking flavonoid containing supplements (and unwilling to cease intake during, and 1 month preceding the trial) or unwilling to maintain existing intake of other supplements.
• High flavonoid intake defined as > 15 portions of flavonoid rich foods per day
• Are currently taking medication or supplements which have a significant impact on the outcome measures.

In addition, any participants with claustrophobia will not be invited to participate in the neuroimaging component of the study. Likewise for metal implants, e.g. pacemaker that precludes MRI.