Objective: To determine whether the levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (AA), total n-3 polyunsaturated fatty acids (PUFAs), and total n-6 PUFAs were changed in patients with dementia or predementia syndrome. Data Sources: PubMed was searched for studies from first date available to July 2011 using the following search terms: (dementia OR cognitive impairment OR mild cognitive impairment) AND (omega-3 OR omega-6 OR polyunsaturated fatty acid OR docosahexaenoic acid OR DHA OR eicosapentaenoic acid OR EPA). The search was limited to literature in English and to human studies. The references of relevant articles and review articles were searched for citations not indexed in PubMed. Study Selection: Studies were included if they measured levels of EPA, DHA, AA, total n-3 PUFAs, or total n-6 PUFAs from peripheral blood tissues in subjects with cognitive deficits (dementia or predementia syndrome) and elderly controls and were published in peer-reviewed journals. The search yielded 10 articles including 2,280 subjects. Data Extraction: The study design, sample size, PUFA levels for both patients and control subjects, sampling tissue, diagnoses and diagnostic criteria for cognitive deficits, and distribution of mean age and gender of included subjects were extracted for each study. Results: In a random-effects model, we found that the levels of EPA (effect size [ES] = -0.47, P <.0001), DHA (ES = -0.33, P = .017), and total n-3 PUFAs (ES = -0.46, P = .001) were decreased in patients with dementia. However, the levels of EPA (ES = -0.44, P = .002), but not DHA or other PUFAs, were significantly lower in patients with predementia syndrome. Conclusions: Our results support the important role of n-3 PUFAs in the pathophysiology of dementia. In addition, the analyses of predementia studies indicate that EPA might be not only a disease-state marker but also a risk factor for cognitive impairment.
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