Docosahexaenoic acid (DHA) is the major fatty acid of neurological and retinal membranes. It makes up more than 30% of the structural lipid of the neuron and is particularly enriched in synaptosomal membranes. A number of seemingly unrelated neuropathological conditions including depression, attention deficit hyperactivity disorder, and dementia have a common association in that patients exhibit a subnormal DHA status. Clinical studies in patients with adrenoleukodystrophy, tong chain hydroxyacyl CoA dehydrogenase deficiency, dyslexia, and Alzheimer's dementia (AD) demonstrated improvements in visual or neurological deficits by elevating circulating DHA levels through a dietary'intervention. In this study, we assessed the circulating DHA status of 1,188 elderly American subjects (mean age of 75 yr) using serum phosphatidylcholine (PC) as the biomarker. Frozen plasma samples obtained in 1985 were extracted with chloroform and methanol, and the phospholipids were separated by high-perlbrmance liquid chromatography. Purified PC fractions were collected, transesterified with methanolic base, and the fatty acid methyl esters were separated by capillary column gas chromatograpy.

Most of the serum PC fatty acids exhibited a normal frequency distribution, but there was a nonnormal distribution of the serum PC-associated DHA and eicosapentaenoic acid (EPA). This skewed distribution reflects the influence of preformed DHA and EPA in the diet, likely from fish consumption, in some members of the population. In fact, there was a significant positive correlation between serum PC-EPA and PC-DHA levels. Following the analysis of the blood samples, we undertook a blinded prospective analysis of the clinical outcomes [both AD diagnosis as well as scores on the Mini-