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Completed

NCT Number: NCT01577004

Do Apolipoprotein E Polymorphisms Influence Risk of Cognitive Decline by Modulating Omega-3 Fatty Acid Metabolism?

BACKGROUND: Compared to the epsilon 2 or epsilon 3 alleles, the epsilon 4 allele of apolipoprotein E (ApoE4) is associated with twice the prevalence of late-onset Alzheimer's disease (AD). Epidemiological studies show that risk of AD varies inversely with consumption of omega-3 fatty acids from fish and seafood. Despite apparently lower fish intake in AD, pooled analysis of the literature shows that plasma and brain docosahexaenoic acid (DHA) is actually the same in AD as in healthy age-matched controls. Fish oil trials in AD are also not convincing. We recently shown that ApoE4 carriers have 41% higher fasting plasma EPA and DHA compared to non-carriers, but the plasma EPA and DHA response to fish oil in ApoE4 carriers was half that seen in non-carriers.

HYPOTHESES: (i) Carriers of ApoE4 have altered metabolism of carbon-13 (13C)-DHA as well as EPA and DHA provided in a dietary supplement. (ii) A dietary supplement of EPA+DHA will improve cognitive performance but only in non-carriers of ApoE4.

OBJECTIVES: In both carriers and non-carriers of ApoE4, to compare whether- i) ApoE4 alters incorporation of 13C-DHA into plasma lipids or its beta-oxidation.

ii) 13C-DHA metabolism changes while on a dietary supplement of EPA+DHA; iii) Better cognitive performance occurs while on EPA+DHA and is linked to raising plasma EPA and/or DHA.

EXPERIMENTAL METHODS: Participants older than 50 y old and not demented were enrolled. DHA metabolism was evaluated using both 13C-DHA and an EPA+DHA supplement (2.4 g/d for 5 mo; n = 20/gp). Before and in the last month of supplementation, plasma uptake and beta-oxidation of 50 mg of 13C-DHA was followed during one month. Blood omega-3 fatty acids was evaluated monthly during the supplementation period. Cognitive testing was performed before and 4 months after starting the omega-3 fatty acid supplement.

IMPLICATIONS: This project will help explain the apparent link that is newly emerging between ApoE polymorphisms, altered omega-3 fatty acid metabolism and risk of cognitive decline, and should help in the development of nutraceutical-based clinical trials using fish oil for the elderly.

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Key information

Conditions

Healthy

Age range

50 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Melanie Plourde

Sherbrooke, Quebec, J1H4C4, Canada

About this study

To come

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • MCI will be defined by Winblad et al. (33), with diagnosis confirmed by a geriatrician through neuropsychological evaluation done within the last 6 months.
  • if diagnosis was done more than 6 months ago, the subject will be re-evaluated before inclusion to confirm MCI rather than conversion to AD.

Exclusion criteria

  • tobacco
  • malnutrition (assessed from blood albumin, haemoglobin and lipids)
  • subjects already taking an EPA+DHA supplements
  • swallowing problems, uncontrolled diabetes (raised fasting glucose, haemoglobin A1c)
  • uncontrolled thyroid disease
  • severe renal failure
  • chronic immune condition or inflammation (raised C-reactive protein, white cell count)
  • cancer
  • recent major surgery or cardiac event
  • uncorrected visual or hearing problems
  • dementia
  • ongoing or past severe drug or alcohol abuse
  • psychiatric difficulties or depression as evaluated by the geriatric depression scale test (34)
  • use of psychotropic medications except for short-acting benzodiazepines taken before sleep.

Treatment and study plan

Omega-3 fatty acid

Dietary Supplement

Subjects will be given four 1 g capsules of fish oil providing 1.4 g/d of EPA and 1.0 g/d of DHA as ethyl esters (Ocean Nutrition, Dartmouth, NS), which is similar to the dose used in previous studies with MCI and AD (20, 21).

Other names: Ocean Nutrition, Dartmouth, NS

Primary outcomes

  1. 13C-DHA incorporation into plasma lipids or beta-oxidation.

    Time frame: one month

    Before and in the last month of supplementation, plasma incorporation and beta-oxidation of 50 mg of 13C-DHA will be followed during one month. Blood and breath samples will be collected at time 0 h, 1 h, 2 h, 4 h, 6 h, 8 h, 24 h, 7 d, 14 d, 21 d, and 28 d.

Secondary outcomes

  1. Cognitive performance compared to baseline

    Time frame: 5 month

    Cognitive testing was done before and 4 months after starting the omega-3 fatty acid supplement.

Sponsors and collaborators

Lead sponsor

Université de Sherbrooke

Other

Registry information

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Apr 13, 2012
Registry last updated
Apr 13, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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