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The Cognitive Ageing Nutrition and Neurogenesis (CANN) Trial

Not Applicable
Completed
Conditions
Subjective Memory Impairment
Mild Cognitive Impairment
Interventions
Dietary Supplement: Placebo
Dietary Supplement: fatty acid/flavonoid blend
Registration Number
NCT02525198
Lead Sponsor
University of East Anglia
Brief Summary

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

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
259
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo group: 12 month daily ingestion of placebo oil and flavonoid-poor matched extract
fatty acid/flavonoid blendfatty acid/flavonoid blendExperimental group: 12 month daily ingestion of 1.5 g EPA+DHA and 500 mg flavonoids
Primary Outcome Measures
NameTimeMethod
Number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System12 months

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.

Secondary Outcome Measures
NameTimeMethod
Attention ability on the Digit Span task12 months

Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)

Cerebrovascular blood flow12 months

To be measured on spectroscopy

Measurement of blood brain barrier permeability8 minutes

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.

Executive function on the Trail Making Task12 months

Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)

Hippocampal volume12 months

To be measured on magnetic resonance imaging

Gut microflora speciation and metabolism12 months

Measured in faecal samples. By extension, we also seek to consider the contribution of the microflora to cognition function and its response to treatment.

Circulating biomarkers of cognition12 months

Biomarkers to include BDNF, β-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine)

Visuospatial ability on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Figure Copy test12 months

Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)

Association between baseline APOE status and number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System12 months

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.

Circulating biomarkers of cardiovascular health12 months

Biomarkers to include BDNF, β-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine)

Language ability on the Boston Naming Test12 months

Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)

Trial Locations

Locations (3)

Beckman Institute, University of Illinois

🇺🇸

Urbana, Illinois, United States

Department of Nutrition, University of East Anglia

🇬🇧

Norwich, Norfolk, United Kingdom

Centre for Human Psychopharmacology, Swinburne Univerity of Technology

🇦🇺

Melbourne, Victoria, Australia

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