A nutritious diet rich in fruits, vegetables, and whole grains and that is low in fat and added sugar can reduce the risks of many chronic conditions, including heart disease, diabetes, obesity, and some forms of cancer. In recent years, investigators have used epidemiologic, animal, and test tube studies and clinical trials to explore whether diet can play a role in preserving cognitive function or even reducing risk of AD.
A long-held theory about aging suggests that, over time, damage from free radicals (molecules that chemically react easily with other molecules) can build up in neurons, causing loss of function. This damage is called oxidative damage. The brain’s unique characteristics, including its high rate of metabolism and its long-lived neurons, may make it particularly vulnerable to oxidative damage. Previous epidemiologic and laboratory studies have suggested that fruits and vegetables that are high in antioxidants might protect the brain against this kind of damage. A group of Harvard Medical School researchers explored this possibility by examining data from more than 13,000 Nurses’ Health Study participants aged 70 and older (Kang et al., 2005). They found that the women who ate the most vegetables—especially green leafy vegetables (like spinach and romaine lettuce) and cruciferous vegetables (like broccoli and cauliflower)—experienced a slower rate of cognitive decline than did women who ate the least vegetables. The scientists were careful to account for other factors that might influence the results, such as use of vitamin supplements, physical activity, smoking and alcohol use, and educational attainment. Interestingly, fruit consumption did not appear to be associated with any change in cognitive ability. The scientists speculate that the abundant antioxidant and folate (a nutrient that appears to be important for proper neural activity and cognitive function) content of the green leafy and cruciferous vegetables was responsible for these results.
As with physical activity studies, these epidemiologic studies can only suggest associations between diet and cognitive performance. That’s why researchers have turned to animal studies to explore in greater detail possible diet and AD relationships. Dogs are a good model for this type of AD research because they can perform sophisticated and complex cognitive tests, their brains accumulate beta-amyloid plaques with age, and the degree of beta-amyloid deposition is related to the severity of cognitive decline. Investigators at the University of Toronto and the University of California at Irvine completed a 2-year study that assessed whether long-term treatment with a combination of “behavioral enrichment” (extra attention and lots of training and stimulation) and a diet rich in antioxidants and mitochondrial cofactors from vitamins E and C and fruit and vegetable extracts could reduce age-related cognitive decline (Milgram et al., 2004; Milgram et al., 2005). This study included both old and young dogs. Some received both the fortified food and enriched environment, some received one or the other enrichment, and some received neither. At the end of the first year, the researchers tested the dogs on two learning tasks. They found that antioxidant supplementation was effective only when it was combined with behavioral enrichment. The 2-year results, however, showed that the supplemented food by itself had a beneficial effect on the older dogs’ ability to perform the learning tasks, suggesting that the effects of the antioxidant supplementation became stronger over time. In both studies, the effects of the treatments were most evident in the dogs who received the dietary as well as the behavioral enrichment. In another similar study with dogs, these same researchers found that an antioxidant-enriched diet improved the performance of older dogs when they performed learning tests for the first time, but not on repeat tests, suggesting that the enriched diet was particularly helpful when the dogs had to process new information (Siwak et al., 2005).
Curcumin is the main ingredient of turmeric, a bright yellow spice used in curry. Scientists are extremely interested in this compound because it has powerful anti-inflammatory and antioxidant properties and can suppress the accumulation of beta-amyloid in brain tissue. In test tube and transgenic mice studies, a research group supported by NIA and the National Institute of Neurological Disorders and Stroke (NINDS) found that curcumin was able to cross the blood-brain barrier and bind directly to beta-amyloid peptides (Yang et al., 2005). These investigators, from the Greater Los Angeles Veterans Affairs Healthcare System, found that the curcumin actually had several different anti-amyloid properties. By binding to the beta-amyloid peptide, curcumin prevented the aggregation of the peptides into oligomers and inhibited the toxic effect of the oligomers (see "How Does AD Begin, and What Causes it to Progress?" for more on the process by which beta-amyloid aggregates into oligomers and ultimately plaques). When fed to aged mice that had significant plaque accumulation, the curcumin was able to reduce amyloid levels and the overall amount of plaque.
This research team also examined the effects of another dietary component—the omega-3 fatty acid called docosahexaenoic acid (DHA), which is found in abundance in some kinds of fish. DHA is a primary component of the membranes of nerve cells in the brain and is involved in multiple brain functions, including nerve cell communication. DHA is reduced in the brains of people with AD, and some evidence suggests that higher levels of DHA in the blood may be protective for dementia and AD (Schaefer et al., 2006). In studies with transgenic mice, the researchers found that deficits in DHA can damage brain biochemistry, structure, and cognitive abilities (Calon et al., 2004). In contrast, a diet high in DHA reduced beta-amyloid and reduced the overall amount of plaque in the brain, especially in the hippocampus and parietal cortex, and reduced the amount of APP, the beta-amyloid precursor protein (Lim et al., 2005; Cole et al., 2005).
Research teams at the University of Southern California, in Los Angeles, and the Mt. Sinai School of Medicine, in New York, also have used transgenic mice to investigate another possible link between diet and cognitive decline and AD. It is known that a calorie-restricted diet slows various aging processes in laboratory animals, so these investigators examined what effect calorie restriction might have on the AD process in transgenic mice. In one study, calorie restriction substantially decreased the accumulation and size of beta-amyloid plaques (Patel et al., 2005). It also reduced the activation of certain glial cells called astrocytes near beta-amyloid plaques. Beta-amyloid plaques in the AD brain are usually surrounded by numerous activated astrocytes. The Mt. Sinai team found that a calorie-restricted diet also promoted the activity of alpha-secretase, the enzyme involved in cleaving APP in a beneficial way. This prevented new beta-amyloid peptides from being formed and plaques from being deposited in brain tissue (Wang et al., 2005).
These studies have provided intriguing hints about possible associations between various dietary elements, oxidative damage and inflammation in brain tissues, and AD pathology. To confirm these results, scientists have turned to clinical trials:
As with other areas of research into lifestyle factors and AD, we have tantalizing hints about particular dietary components but few firm conclusions about diet as a whole and its relationship to cognitive decline and AD. One reason for this is the complexity of the diet. Because a person’s diet has numerous components and varies from day to day, researchers often must rely on supplements to isolate particular factors. Nutrient supplements on their own are not the same as nutrients within the context of whole foods, however, so caution is in order when applying these results to actual dietary patterns. Despite these limitations, findings to date about diet, cognitive decline, and AD are consistent with, and provide additional support for, current recommendations about the components of a nutritious and health-promoting diet.
Many news reports lately have touted the possible beneficial effects of moderate alcohol consumption, especially to prevent heart disease. These helpful qualities are due to the fact that alcohol reduces inflammatory proteins in the blood and increases levels of HDL (the “good” cholesterol).
A growing body of evidence is now suggesting that factors that play an important role in heart disease and stroke also may be important in AD. Could a glass of wine or beer help prevent AD, then?
Several epidemiologic studies have examined this question. They have found that moderate alcohol consumption was not associated with impaired cognitive function and actually is correlated with reduced risk of cognitive decline and AD (Bond et al., 2004; Evans and Bienias, 2005; Ganguli et al., 2005; Luchsinger et al., 2004; Stampfer et al., 2005). As with heart disease, the beneficial effect of alcohol on cognitive abilities may occur because alcohol can reduce inflammatory proteins and increase HDL.
Animal research also has linked certain compounds with beneficial effects on the brain. For example, a team of researchers at the North Shore-Long Island Jewish Institute for Medical Research supported by the National Institute of Mental Health (NIMH), found in test-tube studies that resveratrol, a naturally occurring compound mainly found in grapes and red wine, markedly lowered the level of beta-amyloid in cells (Marambaud et al., 2005). Resveratrol did not inhibit the production of beta-amyloid, but rather promoted its degradation within the cell.
However, these findings come with lots of caveats. For one thing, we don’t know enough about alcohol’s effects on AD pathology to recommend it directly as a way to reduce cognitive decline or AD risk. For another, observational and epidemiologic research can reveal associations, but do not establish cause and effect. These limitations make it hard to say that the alcohol itself is responsible for reducing risk of cognitive decline. Many other factors about participants’ lifestyles and health also may play a role. Another complication is that the studies define “moderate” consumption differently, making it difficult to come to a definite conclusion about whether and how much alcohol may be beneficial.
Finally, it’s important to remember that heavy alcohol consumption has well-established harmful effects, and older people can be more affected by alcohol than younger people.
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