Elsevier

Neurobiology of Aging

Volume 33, Issue 7, July 2012, Pages 1482.e17-1482.e29
Neurobiology of Aging

Abstracts of online article
Effects of omega-3 fatty acids on cognitive performance: a meta-analysis

https://doi.org/10.1016/j.neurobiolaging.2011.12.014Get rights and content

Abstract

Background

Higher intake of omega-3 fatty acids (n-3 FAs) is associated with a reduced risk of Alzheimer's disease (AD) and milder forms of cognitive impairment (e.g. cognitive impairment no dementia [CIND]); however, findings from interventional trials are inconsistent. This meta-analysis examined the neuropsychological benefit of n-3 FAs in randomized double-blind placebo-controlled studies (RCTs) including healthy, CIND, or AD subjects.

Methods

Literature was searched using Medline, Embase, PsycInfo, Cochrane Library, Allied and Complementary Medicine Database (AMED), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to September 2011. Treatment effects were summarized across cognitive subdomains, and effect sizes were estimated using Hedge's g and random effects modeling.

Results

Ten RCTs were combined quantitatively. There was no effect of n-3 FAs on composite memory (g = 0.04 [95% CI: −0.06–0.14], N = 934/812, p = 0.452). When examined by domain, no overall benefit for immediate recall (0.04 [−0.05–0.13], N = 934/812, p = 0.358) was detected; however, an effect in CIND subjects (0.16 [0.01–0.31], N = 349/327, p = 0.034) was found. A benefit for attention and processing speed was also detected in CIND (0.30 [0.02–0.57], N = 107/86, p = 0.035), but not healthy subjects. Benefits for delayed recall, recognition memory, or working memory and executive function were not observed. Treatment did not benefit AD patients as measured by the Mini-Mental State Examination (MMSE) or Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS–cog). No differences in adverse events (AE), dropout, or dropout due to AE between groups were observed.

Conclusions

These results suggest an effect of n-3 FAs within specific cognitive domains in CIND, but not in healthy or AD subjects.

Introduction

As our population has aged, cognitive impairment associated with Alzheimer's disease (AD) and other dementias has become a considerable burden. It is currently estimated that 35.6 million people are living with dementia worldwide (Wimo and Prince, 2010). Many others experience significant cognitive deficits in the absence of the full dementia syndrome, variably described as mild cognitive impairment (MCI) or cognitive impairment no dementia (CIND), with approximately 12% of these individuals converting to dementia each year (Plassman et al., 2008). Despite these alarming statistics, it is estimated that delaying the disease onset by as little as 1 year would spare almost 9.2 million people worldwide from developing dementia by 2050 (Wimo and Prince, 2010).

AD is initially characterized by amnesia and executive dysfunction and progresses to global deficits that ultimately lead to total incapacity (Jicha and Markesbery, 2010). These features are thought to result from aberrant protein aggregation as extracellular amyloid-β plaques and intracellular neurofibrillary tangles are associated with disrupted neurotransmission and deterioration of synaptic integrity (Di Paolo and Kim, 2011). Although milder forms of cognitive impairment may not share this hallmark neuropathology, there appears to be a common deficiency in several key lipid species in the brain and periphery of impaired patients. Cross-sectional studies have consistently reported lower levels of omega-3 fatty acids (n-3 FAs), especially docosahexaenoic acid (DHA), in serum, erythrocyte membranes, and postmortem brain tissue of patients with AD (Conquer et al., 2000, Tully et al., 2003) and CIND (Huang, 2010, Whalley et al., 2008), and evidence suggests that dietary n-3 FA intake is associated with superior performance on neuropsychological testing (Kalmijn et al., 2004, Nurk et al., 2007, Whalley et al., 2004). Prospective studies indicate that higher intake of n-3 FAs is associated with lower rates of cognitive decline and may be protective against the onset of cognitive impairment and neurological morbidity (Devore et al., 2009, Morris et al., 2003, Roberts et al., 2010, van Gelder et al., 2007).

Several clinical trials (Boston et al., 2004, Chiu et al., 2008, Dangour et al., 2010, Freund-Levi et al., 2006, Johnson et al., 2008, Kotani et al., 2006, Quinn et al., 2010, Sinn et al., 2011, Suzuki et al., 2001, Vakhapova et al., 2010, van de Rest et al., 2008, Yehuda et al., 1996, Yurko-Mauro et al., 2010) have investigated the cognitive benefit of n-3 FA therapy in both impaired and nonimpaired patients; however, mixed results have been reported, possibly because of sample heterogeneity or methodological inconsistencies. The effects of n-3 FAs on specific neuropsychological domains have not been investigated previously in a quantitative synthesis. This meta-analysis reports the cognitive benefits of n-3 FA treatment within specific neuropsychological domains across cognitively normal elderly subjects, those with CIND, and patients with AD.

Section snippets

Data sources

All analyses were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Liberati et al., 2009). Literature was searched using the Medical Literature Analysis and Retrieval System Online (MEDLINE; National Library of Medicine, Bethesda, MD), Excerpta Medica Database (Embase; Elsevier, Amsterdam, the Netherlands), PsycINFO (American Psychological Association, Washington, DC), the Cochrane Library (the Cochrane Collaboration, Oxford,

Literature search results

The search strategy returned 1038 unique titles including 3 reports that were hand-selected from reference lists of relevant articles. Of these titles, 442 articles were relevant to n-3 FAs and cognition, dementia, or AD. A total of 433 records were excluded from the 442 relevant articles, 317 of which were not double-blind, placebo-controlled RCTs using n-3 FAs as an intervention, and the remaining 116 were reviews. In total, 10 records were identified as eligible for this meta-analysis (Table

Discussion

This meta-analysis did not find a significant treatment effect of n-3 FAs when memory outcomes were combined. Likewise, n-3 FA treatment did not benefit measures of global cognitive performance (as measured by MMSE and ADAS–cog) in AD patients. When cognitive subdomains were assessed, the use of n-3 FAs did not influence recognition memory, working memory and executive function, immediate recall, delayed recall, or attention and processing speed, although the studies included in these analyses

Conclusions

Omega-3 fatty acid treatment was associated with a small, but significant, benefit for immediate recall and attention and processing speed in subjects with CIND but not in healthy subjects or those with AD. Potential moderators of treatment response such as ApoE genotype and baseline plasma DHA levels could not be investigated from the current literature. Nevertheless, the present findings suggest that the effects of n-3 FAs on cognitive decline are not uniform, and that there is a need to

Disclosure statement

The authors declare no actual or potential conflicts of interest including any financial, personal, or other relationships with other people or organizations within three years of beginning the work submitted that could inappropriately influence (bias) their work.

The authors declare no conflicts of interest regarding institution contracts relating to this research through which these institutions or any other organization may stand to gain financially now or in the future.

Acknowledgements

We acknowledge the Institute of Aging and the CIHR Training Program in Neurodegenerative Lipidomics, the Ontario Graduate Scholarship Program, and the Alzheimer Society Research Program for their support.

The following authors contributed substantially to conception and design (G.M., W.S., K.L.L., N.H.), data collection (G.M., S.A.C.) and analyses, and presentation of data (G.M., W.S., S.A.C., K.L.L., N.H.). All authors revised the paper critically for important intellectual content and gave

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