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Meta-Analysis
. 2012 Jun 13;2012(6):CD005379.
doi: 10.1002/14651858.CD005379.pub3.

Omega 3 fatty acid for the prevention of cognitive decline and dementia

Emma Sydenham  1 , Alan D Dangour, Wee-Shiong Lim
Affiliations
Meta-Analysis

Omega 3 fatty acid for the prevention of cognitive decline and dementia

Emma Sydenham et al. Cochrane Database Syst Rev. .

Abstract

Background: Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA) may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomised controlled trials.

Objectives: To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people.

Search methods: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 6 April 2012 using the terms: "omega 3", PUFA, "fatty acids", "fatty acid", fish, linseed, eicosapentaenoic, docosahexaenoic.

Selection criteria: Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials.

Data collection and analysis: The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) on an intention-to-treat basis, and summarised narratively information on safety and adherence.

Main results: Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up.In two studies participants received gel capsules containing either omega-3 PUFA (the intervention) or olive or sunflower oil (placebo) for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies had cognitive health as their primary outcome; one study of cardiovascular disease included cognitive health as an additional outcome.None of the studies examined the effect of omega-3 PUFA on incident dementia. In two studies involving 3221 participants there was no difference between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention); MD -0.07 (95% CI -0.25 to 0.10). In two studies involving 1043 participants, other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies.The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems. Overall, minor adverse events were reported by fewer than 15% of participants, and reports were balanced between intervention groups. Adherence to the intervention was on average over 90% among people who completed the trials. All three studies included in this review are of high methodological quality.

Authors' conclusions: Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems.Further studies of longer duration are required. Longer-term studies may identify greater change in cognitive function in study participants which may enhance the ability to detect the possible effects of omega-3 PUFA supplementation in preventing cognitive decline in older people.

PubMed Disclaimer

Conflict of interest statement

Alan Dangour is the principal investigator of Dangour 2010 (the Older People And n‐3 Long‐chain polyunsaturated fatty acids (OPAL) study).

ES and W‐S L: None known.

Figures

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'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. Please note there are three studies included in the review.
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'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study. Please note there are three studies included in the review.
1.1
1.1. Analysis
Comparison 1 Mini‐Mental State Examination Score, Outcome 1 MMSE score.
2.1
2.1. Analysis
Comparison 2 Memory ‐ Word learning test, Outcome 1 Immediate recall.
2.2
2.2. Analysis
Comparison 2 Memory ‐ Word learning test, Outcome 2 Delayed Recall.
2.3
2.3. Analysis
Comparison 2 Memory ‐ Word learning test, Outcome 3 Word Recognition.
3.1
3.1. Analysis
Comparison 3 Verbal fluency test, Outcome 1 Number of animals named.
4.1
4.1. Analysis
Comparison 4 Executive Function, Outcome 1 Digit Span Forward.
4.2
4.2. Analysis
Comparison 4 Executive Function, Outcome 2 Digit Span Backward.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

Dangour 2010 {published data only}
    1. Dangour A. The OPAL study: Older people and n‐3 long chain polyunsaturated fatty acids. Current Controlled Trials. http://www.controlled‐trials.com/isrctn/trial/|/0/72331636.html 2005.
    1. Dangour A, Allen E, Elbourne D, Fletcher A, Richards M, Uauy R. Fish consumption and cognitive function among older people in the UK: Baseline data from the OPAL study. The Journal of Nutrition 2009;13(3):189‐202. - PubMed
    1. Dangour AD, Allen E, Elbourne D, Fasey N, Fletcher AE, Hardy P, et al. Effect of 2‐y n‐3 long‐chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double‐blind, controlled trial. American Journal of Clinical Nutrition 2010; Vol. 91, issue 6:1725‐32. - PubMed
    1. Dangour AD, Clemens F, Elbourne D, Fasey N, Fletcher AE, Hardy P, et al. A randomised controlled trial investigating the effect of n‐3 long‐chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n‐3 Long‐chain polyunsaturated fatty acids (OPAL) study protocol. Nutrition Journal 2006; Vol. 5:20. - PMC - PubMed
Geleijnse 2011 {published and unpublished data}
    1. Geleijnse J, Giltay E, Kromhout D. Effects of n‐3 fatty acids on cognitive decline: A randomized, double‐blind, placebo‐controlled trial in stable myocardial infarction patients. Alzheimer's & Dementia 2011;Epub ahead of print:1‐10. [DOI: 10.1016/j.jalz.2011.06.002; PUBMED: 21967845] - DOI - PubMed
    1. Kromhout D. Alpha Omega Trial ‐ Research Plan (study protocol). Available from: http://www.alphaomegatrial.com/protocol_nih.pdf Accessed 29 October 2011.
    1. Kromhout D, Giltay EJ, Geleijnse JM, Alpha Omega Trial Group. n‐3 Fatty Acids and Cardiovascular Events after Myocardial Infarction. New England Journal of Medicine 2010;363:2015‐26. [DOI: 10.1056/NEJMoa1003603] - DOI - PubMed
Van de Rest 2008 {published and unpublished data}
    1. Rest O, Groot CPGM, Geleijnse JM, Kok FJ, Staveren WA, Hoefnagels WHL, et al. Research Protocol: The efficacy of omega‐3 fatty acids in maintaining optimal mental health in elderly people: MEMO study. Unpublished October 2005.
    1. Rest O, Geleijnse JM, Kok FJ, Staveren WA, Beekman ATF, Hoefnagels WHL, et al. The Efficacy of Omega‐3 Fatty Acids on Cognitive Performance and Mental Well‐Being in Elderly People: a Randomized, Double‐Blind, Placebo‐Controlled Trial. Annals of Nutrition and Metabolism 2007;51:76.
    1. Rest O, Geleijnse JM, Kok FJ, Staveren WA, Dullemeijer C, OldeRikkert MGM, et al. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 2008;71(6):430‐8. - PubMed
    1. Rest O, Geleijnse JM, Kok FJ, Staveren WA, Hoefnagels WH, Beekman ATF, et al. Effect of fish‐oil supplementation on mental well‐being in older subjects: a randomized, double‐blind, placebo‐controlled trial. American Journal of Clinical Nutrition 2008;88:706‐13. - PubMed
    1. Rest O, Geleijnse JM, Kok FJ, Staveren WA, Olderikkert MGM, Beekman ATF, et al. Effect of fish oil supplementation on quality of life in a general population of older Dutch subjects: a randomized, double‐blind, placebo‐controlled trial. Journal of the American Geriatrics Society 2009;57(8):1481‐6. - PubMed
Van de Rest 2008 (High) {published data only}
    1. See See Van de Rest 2008.
Van de Rest 2008 (Mod) {published data only}
    1. See Van de Rest 2008.

References to studies excluded from this review

Johnson 2008 {published data only}
    1. Johnson EJ, McDonald K, Caldarella SM, Chung HY, Troen AM, Snodderly DM. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutritional Neuroscience 2008; Vol. 11, issue 2:75‐83. - PubMed
Svetkey 1999 {published data only}
    1. Svetkey LP, Sacks FM, Obarzanek E, Vollmer WM, Appel LJ, Lin PH, et al. The DASH Diet, Sodium Intake and Blood Pressure Trial (DASH‐Sodium): rationale and design. Journal of the American Diet Association 1999; Vol. 99, issue 8 Suppl:S96‐104. - PubMed
Yurko‐Mauro 2010 {published data only}
    1. Yurko‐Mauro K, McCarthy D, Rom D, Nelson E, Ryan A, Blackwell A, et al. Beneficial effects of docosahexaenoic acid on cognition in age‐related cognitive decline. Alzheimer's & Dementia 2010;6(6):456‐64. - PubMed

References to ongoing studies

Aiken 2010 {published data only}
    1. Aiken. [Public title] The Beyond Ageing Project: Phase II: A selective prevention trial using novel pharmacotherapies in an older age cohort at risk for depression; [Scientific title] In older adults (60+ years) at risk for depression, can sertraline and/or omega‐3 fatty acids compared with a placebo, reduce or prevent depressive symptoms, incidence of new cases of depression and/or cognitive decline. WHO Portal (ICTRP) 2010.
Danthiir 2007 {published data only}
    1. Danthiir. An 18 month study investigating the effects of long chain omega‐3 polyunsaturated fatty acids supplementation on cognition and wellbeing in older people (EPOCH). ANZCTR (via ALOIS) 2007:http://www.anzctr.org.au/ACTRN12607000278437.aspx.
    1. Danthiir V, Burns NR, Nettelbeck T, Wilson C, Wittert G. The Older People, Omega‐3, and Cognitive Health (EPOCH) trial design and methodology: A randomised, double‐blind, controlled trial investigating the effect of long‐chain omega‐3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults. Nutrition Journal 2011;10(117):1‐58. [DOI: 10.1186/1475-2891-10-117] - DOI - PMC - PubMed
Vellas 2008 {published data only}
    1. Vellas. Omega‐3 Fatty Acids and/or Multi‐domain Intervention in the Prevention of Age‐related Cognitive Decline (MAPT). ClinicalTrials.gov 2010:http://clinicaltrials.gov/ct2/show/NCT00672685.

Additional references

Appleton 2010
    1. Appleton K, Rogers P, Ness A. Updated systematic review and meta‐analysis of the effects of n‐3 long‐chain polyunsaturated fatty acids on depressed mood. American Journal of Clinical Nutrition 2010;91:757‐70. [DOI: 10.3945/ajcn.2009.28313] - DOI - PubMed
Bazan 2006
    1. Bazan NG. Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends in Neurosciences 2006;29:263‐71. - PubMed
Burns 2009a
    1. Burns A, Iliffe S. Alzheimer's disease. BMJ 2009;338:b158. - PubMed
Burns 2009b
    1. Burns A, Iliffe S. Dementia. BMJ 2009;338:b75. - PubMed
Cole 2010
    1. Cole GM, Frautschy SA. DHA may prevent age‐related dementia. The Journal of Nutrition 2010;140:869‐74. - PMC - PubMed
Dangour 2010a
    1. Dangour AD, Whitehouse PJ, Rafferty K, Mitchell SA, Smith L, Hawkesworth S, et al. B‐vitamins and fatty acids in the prevention and treatment of Alzheimer's disease and dementia: a systematic review. Journal of Alzheimer's disease 2010;22:205‐24. - PubMed
Delis 1987
    1. Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test. New York: Psychological Corporation, 1987.
Ferri 2005
    1. Ferri CP, Prince M, Brayne C, Brodathy H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112‐7. - PMC - PubMed
Folstein 1975
    1. Folstein MF, Folstein SE, McHugh PR. "Mini‐Mental State": a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 1975;12:189‐98. - PubMed
Gillette Guyonnet 2007
    1. Gillette Guyonnet S, Abellan van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M, et al. IANA task force on nutrition and cognitive decline with aging. The Journal of Nutrition, Health & Aging 2007;11:132‐52. - PubMed
Goodglass 1983
    1. Goodglass H, Kaplan E. Assessment of Dysphasia and Related Disorders. Philadelphia, PA: Lea and Febiger, 1983.
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated March 2011]. The Cochrane Collaboration, 2011.. Available from www.cochrane‐handbook.org.
Kromhout 2010
    1. Kromhout D, Giltay EJ, Geleijnse JM, Alpha Omega Trial Group. n‐3 fatty acids and cardiovascular events after myocardial infarction. New England Journal of Medicine 2010;363:2015‐26. [DOI: 10.1056/NEJMoa1003603] - DOI - PubMed
Luchsinger 2004
    1. Luchsinger JA, Mayeux R. Dietary factors and Alzheimer's disease. Lancet Neurology 2004;3:579‐87. - PubMed
MacLean 2005
    1. MacLean CH, Issa AM, Newberry SJ, Mojica WA, Morton SC, Garland RH, et al. Effects of Omega‐3 Fatty Acids on Cognitive Function with Aging, Dementia, and Neurological Diseases. Evidence Report/Technology Assessment No.114 AHRQ Publication No. 05‐E011‐2. Rockville, MD. Agency for Healthcare Research and Quality. February 2005. - PMC - PubMed
Petersen 2001
    1. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Archives of Neurology 2001;58:1985‐92. - PubMed
Pronova correspondence
    1. Pronova BioPharma. Correspondence with Director of Medical Affairs 08/03/11.
Raina 2008
    1. Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Annals of Internal Medicine 2008;148:379‐97. - PubMed
Ritchie 2000
    1. Ritchie K, Touchon J. Mild cognitive impairment: conceptual basis and current nosological status. Lancet 2000;355(9199):225‐8. - PubMed
Rojas 2003
    1. Rojas CV, Martinez JI, Flores I, Hoffman DR, Uauy R. Gene expression analysis in human fetal retinal explants treated with docosahexaenoic acid. Investigate Ophthalmology and Visual Science 2003;44:3170‐7. - PubMed
SACN 2004
    1. Scientific Advisory Committee on Nutrition. Advice on fish consumption: benefits & risks. London: The Stationery Office, 2004. [ISBN: 0‐11‐243083‐X]
Seven Seas correspondence
    1. Marketing Department. Seven Seas Ltd. 02/03/11.
Uauy 2006
    1. Uauy R, Dangour AD. Nutrition in brain development and aging: role of essential fatty acids. Nutrition Reviews 2006;64:S24‐33; discussion S72‐91. - PubMed
Van der Elst 2005
    1. Elst W, Boxtel MP, Breukelen GJ, Jolles J. Rey's verbal learning test: normative data for 1855 healthy participants aged 24‐81 years and the influence of age, sex, education, and mode of presentation. Journal of the International Neuropsychological Society 2005;11:290‐302. - PubMed
Van der Elst 2006
    1. Elst W, Boxtel MP, Breukelen GJ, Jolles J. Normative data for the Animal, Profession and Letter M Naming verbal fluency tests for Dutch speaking participants and the effects of age, education, and sex. Journal of the International Neuropsychological Society 2006;12:80‐9. - PubMed
Wechsler 1981
    1. Wechsler D. Manual for the Adult Intelligence Scale‐Revised. New York: Psychological Corporation, 1981.

References to other published versions of this review

Lim 2005
    1. Lim WS, Gammack JK, Niekerk J, Dangour AD. Omega 3 fatty acid for the prevention of dementia (Protocol). Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD005379] - DOI - PubMed
Lim 2006
    1. Lim WS, Gammack JK, Niekerk JK, Dangour AD. Omega 3 fatty acid for the prevention of dementia. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD005379.pub2] - DOI - PubMed

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