The Cognitive Ageing Nutrition and Neurogenesis (CANN) Trial

Study Overview
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Brief Summary
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There is a dearth of research which takes a multi-compound approach to dietary interventions, in humans, aimed at improving outcome measures of cognition. Animal research in particular points towards fatty acids and flavonoids having a potentiating effect on each other, and possibly even being synergistic. Thus, study products will be administered in the present trial comprising both of these compounds, with a view to investigating their potential effects on cognition in older adults with mild cognitive impairment (MCI) or subjective memory impairment (SMI).

Detailed Description
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240 participants, aged 55 or above, will be recruited (120 Norwich, 120 Melbourne; to include both MCI and SCI participants). Participants will be asked to take the study food each day for 12 months, and to come to the clinical assessment unit on 3 occasions, at baseline, 3 months and 12 months, to complete a cognitive task battery such that their performance may be investigated in the context of the intervention. Urine, blood and faecal samples will be collected and magnetic resonance imaging (MRI) will be applicable to half of each population (i.e to 60 MCI and 60 SCI, 30 of each at Norwich and Melbourne).

Official Title
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A Randomised Controlled Trial in 'At Risk' Humans Investigating the Cognitive Benefits of a Combined Flavonoid/Fatty Acid Intervention and Underlying Mechanisms of Action: The COGNITIVE AGING NUTRITION and NEUROGENESIS (CANN) Trial

Conditions
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Mild Cognitive Impairment, Subjective Memory Impairment

Intervention / Treatment
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* Dietary Supplement: fatty acid/flavonoid blend
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female, aged ≥ 55 years Mild cognitive impairment (MCI) or subjective memory impairment (SMI) with no indication of clinical dementia or depression Willing and able to provide written informed consent. Understands and is willing and able to comply with all study procedures. Fluent in written and spoken English. In good general health including blood biochemical, haematological and urinalysis within the normal range at screening (as judged by the clinical advisor) Normal, or corrected to normal vision and hearing Right handed, for MRI Stable use of any prescribed medication for at least four weeks Exclusion Criteria: Diagnosis of Alzheimer's disease (AD) or other form of dementia or significant neurological disorder Parent or sibling who developed premature dementia <60y (suggestive of a familial monogenic form of cognitive decline) Past history or MRI evidence of brain damage including significant trauma, stroke, learning difficulties or serious neurological disorder, including loss of consciousness > 24 hours History of alcohol or drug dependency within the last 2 years Other clinically diagnosed psychiatric disorder likely to affect the cognitive measures (as judged by clinical adviser) Existing diagnosed gastrointestinal disorders likely to impact on absorption of flavonoids and fatty acids (as judged by clinical adviser) Major cardiovascular event, e.g. myocardial infarction or stroke, in the last 12 months Carotid stents or severe stenosis Known allergy to fish or any other component in the intervention supplements Existing medical conditions likely to affect the study measures (as judged by clinical adviser) Uncontrolled hypertension (Systolic Blood Pressure (SBP) >140mmHg, Diastolic Blood Pressure (DBP) >90mmHg) BMI >40kg/m2

Ages Eligible for Study
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Minimum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo group: 12 month daily ingestion of placebo oil and flavonoid-poor matched extract | Dietary Supplement: Placebo<br>* see arm description<br>|
| Experimental: fatty acid/flavonoid blend<br>Experimental group: 12 month daily ingestion of 1.5 g EPA+DHA and 500 mg flavonoids | Dietary Supplement: fatty acid/flavonoid blend<br>* see arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System | The CDR Computerized Cognitive Assessment System will be used to measure the cognitive effects of the treatments. The battery is sensitive to bidirectional cognitive change including trials in MCI, dementia and SMI. There is strong converging evidence that one particular aspect of performance, namely the number of false positive responses during a picture recognition task, is particularly sensitive to hippocampal integrity (based on activation of the dentate gyrus during the task, and specific decrements in conditions associated with poorer hippocampal function). This will form the primary outcome in this study. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hippocampal volume | To be measured on magnetic resonance imaging | 12 months | 
| Gut microflora speciation and metabolism | Measured in faecal samples. By extension, we also seek to consider the contribution of the microflora to cognition function and its response to treatment. | 12 months | 
| Association between baseline APOE status and number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System | We will assess the impact of intervention in respect to presence or absence of APOE 4 gene across participants, which is a risk factor for dementia. | 12 months | 
| Circulating biomarkers of cognition | Biomarkers to include BDNF, β-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine) | 12 months | 
| Circulating biomarkers of cardiovascular health | Biomarkers to include BDNF, β-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine) | 12 months | 
| Language ability on the Boston Naming Test | Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment) | 12 months | 
| Visuospatial ability on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Figure Copy test | Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment) | 12 months | 
| Attention ability on the Digit Span task | Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment) | 12 months | 
| Executive function on the Trail Making Task | Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment) | 12 months | 
| Cerebrovascular blood flow | To be measured on spectroscopy | 12 months | 
| Measurement of blood brain barrier permeability | Allows testing of the hypothesis that the test food will help improve BBB permeability through its action on endothelial function. Six axial slices will be measured every 1.34 seconds for 8 minutes. | 8 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild cognitive impairment, Subjective memory impairment, Dementia, Flavonoids, Fatty acids, Cognition, Gut microflora