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Objective: To examine the association of plasmatic and erythrocyte concentrations polyunsaturated fatty acids (PUFA) with both cognitive status and decline., Design: Longitudinal observational cohort study., Setting: Memory Clinic of Lyon Sud university hospital., Participants: 140 patients, aged 60 and older, were referred to the memory clinic, and successively included in the cohort, between March 2010 and February 2014., Measurements: Concentration of ω-3 PUFA (eicosapentaenoic: EPA and docosahexaenoic: DHA) and ω-6 PUFA (arachidonic: AA), were measured at baseline in plasma and in the erythrocytes membrane. Cognitive status was assessed using the mini mental state examination (MMSE), at baseline and every six months during follow-up. The median follow-up period was of 11,5 months., Results: Compared to participants with minor neurocognitive disorders (MMSE≥24), participants with major neurocognitive disorders (NCD) had lower plasmatic concentrations of EPA and DHA (p<0.05) at baseline. Erythrocyte AA and DHA concentrations were significantly lower in patients with cognitive decline (defined as a ≥2 points loss of MMSE per year), while no difference in plasmatic concentrations was observed., Conclusions: Our study suggests that ω-3 PUFA plasma concentrations (mainly EPA and DHA) could be associated with cognitive status in older people. Moreover, in this exploratory study, lower erythrocyte PUFA concentrations (AA and DHA) were associated with accelerated decline and could be proposed as a surrogate marker for prediction of cognitive decline., Competing Interests: The authors declare having no conflicts of interest related to this work. Authors’ disclosures available online. No funder was requested. The “Hospices Civils de Lyon” had only committed as promoter.