N° 16 | October 2007

Mediterranean diet and risk of Alzheimer’s disease

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Diet may play an important role in the causation and prevention of Alzheimer’s Disease (AD) but epidemiological data on diet and AD have been conflicting[1]. Higher intake of vitamins C, E , flavonoids, unsaturated fatty acids, fish, higher levels of B12 and folate, modest to moderate ETOH and lower total fats have been related to a lower risk of AD or slower cognitive decline[1]. At the same time, other studies have found no association between risk for AD or cognitive decline and either antioxidants, such as vitamins C, E and carotenes or fat or levels of B12[1].

Part of the explanation for the inconsistent findings could be the examination of each individual food or nutrient separately from the other elements of the diet. The alternative approach would be to investigate the effect of the whole diet or composite dietary patterns because individuals do not consume foods or nutrients in isolation but rather as components of their daily diet. Defining diet by composite dietary patterns has the ability to capture its multidimensionality because patterns can integrate complex or subtle interactive effects of many dietary constituents. For example, it has been shown that high fish consumption may have a beneficial effect on blood pressure, cholesterol and tendency to form clots only if it is part of a low fat diet. As a different example, the habit of adding a lot of olive oil in salads may be beneficial partially via increasing the total vegetable intake. Such composite dietary pattern analysis has recently received growing attention in relation to many non-neurological diseases (i.e. cirrhosis or various cancers). One such pattern is the Mediterranean diet (MeDi), which has received increased attention in recent years because of converging evidence relating it to lower risk for cardiovascular disease, several forms of cancer and overall mortality[2]. Despite the advantages of the composite dietary pattern approach, previous research in the neurological literature in general, but also in AD in particular, has focused only on individual dietary components.

The MeDi is characterized by high intake of vegetables, legumes, fruits and cereals; high intake of unsaturated fatty acids (mostly in the form of olive oil in salad dressing and cooking) but low intake of saturated lipids; a moderately high intake of fish; a low-to-moderate intake of dairy products (mostly in the form of cheese or yogurt); a low intake of meat and poultry; and a regular but moderate amount of ethanol, primarily in the form of wine and generally during meals. Therefore, the MeDi seems to include many of the components reported as potentially beneficial for AD and cognitive performance in some of the previous literature.

We sought to investigate the association between MeDi and risk for AD[3]. A total of 2,258 community-based nondemented elderly individuals in New York were prospectively evaluated every 1.5 years. There were 262 subjects that developed AD cases during the course of 4 (0.2– 13.9) years of follow-up. We found that higher adherence to the MeDi was associated with lower risk of AD: Each additional unit of the MeDi score was associated with ~10% less risk of developing AD. Compared to subjects in the lowest MeDi adherence tertile, subjects in the middle MeDi adherence tertile had ~20% less risk of developing AD, while those at the highest tertile had ~40% less risk of developing AD, with a significant a trend for a dose-response effect. Adjusting for a series of potential factors that could confound this association did not change the results. In analyses investigating the contribution of individual dietary components, mild to moderate alcohol consumption and higher vegetable consumption were the elements mostly driving the MeDi effect. However, additional analyses suggested that the overall composite dietary pattern of the MeDi may capture more than its individual parts.

In another study we wanted to investigate possible biological mechanisms via which the MeDi may protect from AD[4]. Given that in previous literature higher adherence to the MeDi has been associated with lower cardiovascular disease, which in turn may be related to AD, we hypothesized that the relation between MeDi and AD could be mediated by cardiovascular mechanisms (i.e. stroke, diabetes, hypertension, heart disease, lipid levels). However, we found that the MeDi’s effect in cardiovascular diseases was not the reason for its protective action for AD. A possible explanation for this finding are the limitations in measuring cardiovascular disease with enough precision and accuracy.

Conclusions

Research on dietary effects in AD have so far focused on individual foods and nutrients and results have been conflicting. Higher adherence to the composite dietary pattern of MeDi is associated with a reduced risk for developing AD. Mild / moderate alcohol and vegetable consumption seem to be the elements mostly responsible for this effect but the association seems to be driven mostly by the whole MeDi pattern, rather than its individual dietary components. The association between MeDi and AD is not fully mediated by cardiovascular diseases. This could be the result of additional biological mechanisms being implicated: the MeDi may be resulting not only in more favorable cardiovascular disease profile but also in reduction of oxidative stress and in less inflammation, all mechanisms potentially important for AD pathogenesis.

1. Luchsinger, J.A. and R. Mayeux, Dietary factors and Alzheimer’s disease. Lancet Neurol, 2004. 3(10): p. 579-87.
2. Trichopoulou, A., et al., Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med, 2003. 348(26): p. 2599-608.
3. Scarmeas, N., et al., Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol, 2006. 59(6): p. 912-921.
4. Scarmeas, N., et al., Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol, 2006. 63(12): p. 1709-17.

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