The results of studies regarding these issues have produced conflicting results. One study has found that the more fat consumed in a meal, the greater the risk of developing AD.13 On the contrary, a famous Rotterdam study showed that a high total intake of saturated fat and cholesterol was not associated with an increased risk of dementia.14
With respect to diet and fat intake, we must consider the differences in the types of dietary fat. Namely, it appears that saturated and polyunsaturated fats have apparently opposite effects on cognitive performance. In animal experiments, feeding high levels of saturated fat can result in learning and memory impairments,8 in contrast high levels of polyunsaturated fatty acids result in better cognitive function. Thus, we first review the possible AD preventive role of omega-3 fatty acids.
Omega-3 fatty acids
Epidemiological evidence suggests that dietary consumption of the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish or fish oil, may modify the risk for dementing illnesses including AD. It is clear that DHA is the predominant n-3 fatty acid found in the brain and that EPA plays an important role as an anti-inflammatory precursor.15
Although omega-3 fatty acids are present in plant-based sources such as alpha-linolenic acid (ALA), here we focus mainly on the animal-derived long chain n-3 polyunsaturated fatty acids (EPA, DHA). The pathway for the metabolic conversion of ALA to DHA involves the sequential utilization of delata-6, 5- and 4-desaturateses along with elongation reactions (Fig. 1). The conversion of ALA to EPA and DHA is limited in humans and has been estimated to be anywhere from less than 1% to 6%.16 Interestingly, DHA can also be retroconverted to EPA at rates of about 10% in humans.17
EPA is found primarily in cholesterol ester, triglycerides and phospholipids. DHA is found primarily in phospholipids, and is highly concentrated in the cerebral cortex, retina and testes. In fact, DHA makes up a large proportion of the brain’s lipids, and is the predominant n-3 fatty acid found in brain. The structural predominance of DHA in the brain suggests functional significance.18 Both DHA and EPA can be linked with many aspects of neural function, including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression.15
It has been said that the present western diet is deficient in n-3 fatty acids compared to that on which our genetic patterns were established. This deficiency is explained in terms of decrement in consumption of fish and wild game, and also the increment of the consumption of plant-derived oils, which contain large amounts of n-6′s and minimal n-3′s. Some common vegetable oils, including soybean, canola and flax seed oil, are concentrated sources of ALA in the diet, while fatty fish, such as halibut, mackerel, herring, and salmon are concentrated sources of EPA and DHA. Other sources of dietary n-3 fatty acids are nuts, seeds, fruits, vegetables, egg yolks and meat15 (Table 2).
Table 2. Foods abundant in omega-3 fatty acids (Modified from Young G et al.15)
| Anchovy, European||0.6|| 0.9||–|
| Mackerel, Pacific and jack||0.6|| 0.9||Trace|
| Salmon, Atlantic, farmed||0.6|| 1.3||Trace|
| Trout, rainbow, farmed||0.3|| 0.7||Trace|
| Tuna, fresh, bluefin||0.3|| 0.9||–|
| Oyster, Pacific||0.4|| 0.3||Trace|
| Cod liver oil||6.9||11.0|| 0.9|
| Herring oil||6.3|| 4.2|| 0.8|
|Nuts and seeds|
| Butternuts, dried||–||–|| 8.7|
In the USA, it has been recommended that EPA and DHA be consumed at an intake of 0.65 g/day, which is a 4-fold increase from the current level of consumption of 0.1–0.2 g/day.19 Even in Japan, where seafood has traditionally been consumed at very high levels, the ration of n-6 to n-3 fatty acids is increasing as diets become more Westernized, particularly among young people.20
It has long been suggested that AD is associated with brain lipid defects. Blood levels of omega-3 fatty acids of individuals with existing AD have been investigated. One study suggests an inverse association between cognitive decline and ratio of n-3/n-6 fatty acids in red blood cell membranes.21 Similarly, several studies demonstrated the decreased blood levels of omega-3 fatty acids in AD patients, however, the reason for it is unclear. There are three known studies in which AD or other dementia patients have been supplemented with long-chain omega-3 fatty acids (EPA and/or DHA). All of the three reported from Japan showed the efficacy of their interventions.15
More recently, epidemiological studies have suggested that high fish and/or omega-3 fatty acid consumption is inversely associated with cognitive impairment, cognitive decline and/or development of dementia such as AD.22–24
On the other hand, diabetes as an AD risk factor has attracted attention from researchers because of the following reasons.25 First, glucose regulatory mechanisms can also affect amyloid precursor protein (APP).26 Second, the insulin degrading enzyme can break down Aβ as well as insulin.27 Third, insulin also reduces intracellular accumulation of Aβ by accelerating APP trafficking.28 Adding further links between diabetes and AD is other study that has found that type II diabetes is associated with a low unsaturated : saturated fat intake ratio.29 Several researchers reported that saturated and trans-fatty acids increase insulin resistance, whereas mono- and poly-unsaturated fats decrease resistance and offer protection against diabetes.29,30 In obese and diabetic individuals, there is a marked decrease in the clearance and metabolism of cholesterol-rich lipoproteins from plasma. Additionally, it has been reported that individuals with type II diabetes who posses ApoE ɛ4 allele have twice the risk of developing AD as compared with non-diabetic with ApoE ɛ4.31 Taking these findings together, it appears that abnormalities in glucose metabolism may have some effects on cognitive performance.