. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006 Nov;63(11):1545-50. PubMed.

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  1. The prospective study of Ernst Schaefer et al. suggests an interesting link between blood docosahexaenoic acid (DHA) and the onset of all-cause dementia. This is the follow-up of preliminary findings published in a research letter in 1999 (Kyle et al., 1999). No association was observed when higher quartiles of blood DHA were compared to the lowest quartile after full adjustment. However, compared with the lowest three quartiles, blood DHA in the highest quartile was associated with a lower risk of developing all-cause dementia later in life, thereby having a predictive value. A similar inverse association was observed in Alzheimer disease (AD) but did not reach statistical significance. Nevertheless, it agrees well with previous observations relating low blood DHA with cognitive decline (Heude et al., 2003 (EVA prospective study) or AD (Tully et al., 2003 [case-control study]). However, other investigators do not report any inverse relationship between blood DHA and the incidence of cognitive decline or dementia (Laurin et al., 2003).

    Low consumption of DHA is a well-known risk factor for cardiovascular diseases (Schmidt et al., 2005), and the present study suggests that it is a risk factor for dementia as well. It is thus tempting to speculate that the neuroprotective effect of DHA observed by Schaefer et al. involved an improvement of cardiovascular function of subjects included in the highest quartile of blood DHA. Therefore, it would have been interesting to determine the impact of adjusting relative risks for history of cardiovascular diseases (and other potential confounding variables such as smoking and alcohol intake).

    Blood DHA can be found as free fatty acids or esterified fatty acid in different types of phospholipids, cholesterol esters, triglycerides, or lipoproteins. It can also be found incorporated into the phospholipids of red cell membranes. Dr Schaefer's study is focused on plasma DHA incorporated into phosphatidylcholine, which is thought to be transported by high-density lipoproteins. On the other hand, the studies from Heude et al., Tully et al., and Laurin et al. have measured DHA into the erythrocyte membrane and cholesteryl esters fraction, and total plasma phospholipids, respectively (Heude et al., 2003, Tully et al., 2003, Laurin et al., 2003). These variations in methodology may account for some of the diverging conclusions and might be important if we formulate the bold hypothesis that blood DHA can be "good" or "less good" for the brain depending on which fraction it is bound to (just like blood cholesterol). For instance, the capacity of blood DHA to be transported into the brain can depend on its distribution within blood compartments (Rapoport, 2001). Blood DHA pools might also differ in their long-term stability and might be more or less a good assessment of chronic dietary consumption or fatty acid metabolism. Therefore, to supplement the exciting results of Dr Schaefer’s team, it would be interesting to perform analyses of DHA found in all those different blood compartments to obtain a full picture of the role of this important omega-3 fatty acid in relation to brain health and AD.

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