The long-chain ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are potential candidates for interventions to delay Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at determining whether plasma levels of EPA or DHA predict atrophy of medial temporal lobe (MTL) gray matter regions in older subjects.

A total of 281 community dwellers from the Three-City Study, aged 65 years or older, had plasma fatty acid measurements at baseline and underwent MRI examinations at baseline and at 4 years. We studied the association between plasma EPA and DHA and MTL gray matter volume change at 4 years.

Higher plasma EPA, but not DHA, was associated with lower gray matter atrophy of the right hippocampal/parahippocampal area and of the right amygdala (p < 0.05, familywise error corrected). Based on a mean right amygdala volume loss of 6.0 mm(3)/y (0.6%), a 1 SD higher plasma EPA (+0.64% of total plasma fatty acids) at baseline was related to a 1.3 mm(3) smaller gray matter loss per year in the right amygdala. Higher atrophy of the right amygdala was associated with greater 4-year decline in semantic memory performances and more depressive symptoms.

The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved in the association between EPA and cognitive decline and depressive symptoms.