Omega-3 fatty acids and cognitive decline: modulation by ApoE4 allele and depression Cécilia Samieri a,d, *, Catherine Féart a,d , Cécile Proust-Lima c,d , Evelyne Peuchant e,f , Jean-François Dartigues b,d , Hélène Amieva b,d , Pascale Barberger-Gateau a,d a INSERM, U897, Department of Nutritional Epidemiology, Bordeaux, F-33076, France b INSERM, U897, Department of Aging, Bordeaux, F-33076, France c INSERM, U897, Department of Biostatistics, Bordeaux, F-33076, France d University Victor Segalen Bordeaux 2, ISPED, 146 Rue Léo Saignat, Bordeaux, 33076, France e INSERM, U876, 146 Rue Léo Saignat, Bordeaux, F-33076, France f CHU de Bordeaux, Hôpital Saint-André, Department of Biochemistry, 1 Rue Jean Burguet, Bordeaux, F-33075, France Received 17 December, 2009; received in revised form 25 January 2010; accepted 28 March 2010 Abstract Long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may slow cognitive decline. The 4 allele of the ApolipoproteinE (ApoE), the main genetic risk factor for Alzheimer’s disease, and depressive symptoms, which are frequently associated with cognitive impairment in older persons, may modify this relationship. We estimated the associations between EPA and DHA plasma levels and subsequent cognitive decline over 7 years, taking into account ApoE-4 status and depressive symptoms, in a prospective population-based cohort. Participants ( 65 years, n = 1,228 nondemented at baseline) were evaluated at least once over three follow-up visits using four cognitive tests. Plasma EPA was associated with slower decline on Benton Visual Retention Test (BVRT) performances in ApoE-4 carriers, or in subjects with high depressive symptoms at baseline. Plasma DHA was associated with slower decline on BVRT performances in ApoE-4 carriers only. EPA and DHA may contribute to delaying decline in visual working memory in ApoE-4 carriers. In older depressed subjects, EPA, but not DHA, may slow cognitive decline. © 2010 Elsevier Inc. All rights reserved. Keywords: Aging; Apolipoprotein E4; Cognition; Cohort studies; Depressive symptoms; Longitudinal survey; Nutritional status; Omega-3 fatty Acids Late-onset Alzheimer’s disease (AD) is a multifactorial disease resulting from the effect of aging and a complex interaction of both genetic and environmental risk factors (Blennow et al., 2006). Carriers of the 4 allele of the apolipoprotein E (ApoE) gene, the main genetic risk factor for AD, may show accelerated memory decline long before AD diagnosis (Caselli et al., 2009). In the absence of etio- logic treatment for AD, the identification of modifiable environmental factors that could slow cognitive decline preceding dementia or AD, such as nutritional factors, has aroused increasing interest (Gomez-Pinilla, 2008). The po- tential preventive role of long-chain omega-3 fatty acids (n-3 PUFA), through regular consumption of fish as their main dietary source, has been suggested by several longi- tudinal studies (Cunnane et al., 2009), and some of which have found a nutrient-gene interaction with ApoE-4 status (Schipper, 2009). Few studies relied on blood biomarkers of long-chain n-3 PUFA (Beydoun et al., 2007; Dullemeijer et al., 2007; Heude et al., 2003; Kroger et al., 2009; Whalley et al., 2008), which may be more accurate than dietary variables in assessing nutritional exposure. While the long- chain n-3 PUFA derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may exert different roles on pathological brain aging, consistent with their potentially * Corresponding author at: Equipe Epidémiologie nutrition et des com- portements alimentaires, INSERM, U897, Université Bordeaux 2, ISPED case 11, 146 rue Léo-Saignat, F-33076 Bordeaux cedex, France. Tel.: + (33) 5 57 57 95 38; fax: + (33) 5 57 57 14 86. E-mail address: Cecilia.Samieri@isped.u-bordeaux2.fr (C. Samieri). Neurobiology of Aging xx (2010) xxx www.elsevier.com/locate/neuaging 0197-4580/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2010.03.020 ARTICLE IN PRESS