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The Effects of Long-Term Omega-3 Fatty Acid Supplementation on Cognition and Alzheimer's Pathology in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-Analysis

Article type: Research Article

Authors: Hooijmans, Carlijn R.a | Pasker-de Jong, Pieternel C.M.b | de Vries, Rob B.M.a | Ritskes-Hoitinga, Merela

Affiliations: [a] Radboud University Nijmegen Medical Centre, Central Animal Laboratory and 3R Research Centre, Nijmegen, The Netherlands | [b] Radboud University Nijmegen Medical Centre, Department of Epidemiology, Biostatistics and HTA, Nijmegen, The Netherlands

Correspondence: [*] Correspondence to: Carlijn R. Hooijmans, Radboud University Nijmegen Medical Centre, Central Animal Laboratory and 3R Research Centre, Geert Grooteplein Noord 29, Route 231, 6525 EZ Nijmegen, The Netherlands. Tel.: +0031 243668364; Fax: +0031 243616375; E-mail: [email protected].

Keywords: Alzheimer's disease, amyloid-β peptides, animal models, cognition, docosahexaenoic acid, omega-3 fatty acids, pathology, systematic review

DOI: 10.3233/JAD-2011-111217

Journal: Journal of Alzheimer's Disease, vol. 28, no. 1, pp. 191-209, 2012

Accepted 26 August 2011
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Published: 12 January 2012
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Supplementary Materials:

Supplementary Materials.

Abstract

To date, only a few randomized clinical trials (RCTs) have investigated the effects of omega-3 fatty acids (FA) on Alzheimer's disease (AD). Some of these studies demonstrated that patients with very mild AD or mild cognitive impairment benefit from omega-3 FA treatment, but none showed significant improvements in cognitive function in patients with moderate or advanced AD. All these RCTs had a relatively short duration of supplementation, however, and we hypothesized that this might be one of the reasons why no effects of omega-3 FA supplementation could be observed in patients with “moderate” or “advanced” AD. Animal studies offer better possibilities for controlled long-term supplementation than clinical studies. Therefore, we performed a systematic review (SR) and meta-analysis of the literature that focused on effects of the relatively long-term omega-3 FA supplementation (minimum period; 10% of average total lifespan) on cognitive impairment, amyloid-β pathology, and neuronal loss in animal models of AD. This SR shows that long-term omega-3 FA supplementation decreased the omega-6/omega-3 FA ratio and reduced the amount of amyloid-β in experimental animal models of AD. Omega-3 FA supplementation also improved cognitive function; this effect appeared larger in rats compared to mice, and in males compared to females. Moreover, omega-3 FA supplementation diminished the amount of neuronal loss, especially in female animals. The results of this SR indicate that it might be worthwhile to perform new clinical trials with long-term omega-3 FA supplementation in AD patients.

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