Alzheimer’s disease (AD), the most common cause of dementia among older people, is a progressive brain disease that slowly destroys memory and thinking skills. In most people with AD, symptoms first appear after age 60. Recent estimates by the U.S. National Institute on Aging are that as many as 2.4 to 4.5 million Americans are living with AD.
WHAT CAUSES ALZHEIMER’S DISEASE?
Although the causes of AD are not understood, damage to the brain begins as many as 10 to 20 years before problems are evident. Two abnormal structures—plaques and tangles—in brain contribute to the deterioration of nerve cells (neurons) characteristic of the disease. Plaques are deposits of the abnormal protein beta-amyloid that accumulate between neurons. Neurofibrillary tangles, composed of the protein tau, form inside dying cells. They develop deep in the brain in an area that is vital for memory consolidation. As plaques and tangles form in particular brain areas (see illustration), healthy neurons lose their ability to function and communicate and they eventually die. This damaging process spreads to the hippocampus, which is essential for learning, emotions and forming memories. The affected brain regions begin to shrink, and as damage becomes severe, brain tissue shrinks significantly. It is important to note that as brains age, tangles and plaques form in both normal individuals and patients with AD. Plaques are not a specific marker of cognitive impairment as there is no correlation between their number and AD severity. Although there is no association between plaques and tangles in the hippocampus and cognitive functions unrelated to memory, they are implicated in the decline of memory function over time in AD. Research so far indicates that these lesions likely represent an effect rather than a cause of the disease.
WHAT FACTORS AFFECT THE CHANCE OF DEVELOPING ALZHEIMER’S DISEASE?
The factors related to the chance of developing AD include aging, genetics—which accounts for over 50% of the variance in adult cognitive abilities—and environmental factors such as pesticides, metals, head injuries, lifestyles and dietary habits. Diseases like the metabolic syndrome and diabetes also make AD more likely. People with diabetes, for example, have up to a 65% higher chance of developing AD. Dementia-related factors caused by insulin resistance, which occurs when tissues become unresponsive to the effects of insulin, include not only diabetes but obesity or central adiposity, dyslipidemia, inflammation, hypertension, ischemia (restricted blood supply) and cardiovascular disease. The claim that diabetes is a direct factor related to development of AD has recently been challenged. Both vascular (related to blood vessels) factors and vascular disease are associated with vascular dementia and AD. In addition, conditions such as high total cholesterol and LDL-cholesterol concentrations are associated with a faster cognitive decline in patients with AD. Genes also contribute to the chance of developing AD. The best-known genetic characteristic linked to AD is a variant of the gene for a blood protein called ApoE. Some 40 to 70% of all people who develop late-onset AD carry this gene.
IS THERE A LINK BETWEEN DIET AND ALZHEIMER’S DISEASE PREVENTION?
Large population studies that link nutrition to AD suggest that a shortage of nutrients such as the long-chain omega-3 fatty acids found in fish, several B vitamins and antioxidants increases the chance of developing the disease. On the other hand, individuals with diets rich in fish, the food with the most docosahexaenoic acid (DHA), have a significantly lower chance of developing dementia and AD. Low DHA levels are associated with dementia, and low concentrations of eicosapentaenoic acid (EPA) and DHA in elderly populations increase the chance of accelerated cognitive decline and death from all causes.
Although short-term treatment of healthy elderly people with EPA and DHA does not appear to affect mental wellbeing, dietary habits that include a higher intake of long-chain omega-3s may bring certain health benefits. The brain is highly dependent on DHA for its structure and function, and low amounts in the brain have been linked to depression, schizophrenia, memory loss and a higher chance of developing AD. Moreover, the brains of patients who died with AD had significantly less DHA compared with patients not having AD at death. Several studies reported that people who consume two or more fish meals per week have a reduced chance of dementia, AD and cognitive decline, or the delayed onset of dementia. A recent unpublished study reported that older adults with mild memory issues, but no signs of AD, had improved memory tests after they consumed nearly 1 g/day of DHA for 6 months.
Nutritionists have long endorsed fish as part of a heart-healthy diet, and now studies suggest that seafood omega-3s are pivotal in preventing heart disease and many other chronic diseases. Most Western diets are relatively deficient in long-chain omega-3s and excessive in omega-6 fatty acids compared with the diet on which humans originally established their genetic patterns. The amount of dietary omega-3s consumed daily by the general population in the U.S. is very low, about 1.6 grams, with alpha-linolenic acid (ALA) accounting for nearly 90% of it. Although our bodies have the enzymes necessary to make the more biologically active EPA and DHA from ALA, very little ALA is converted to EPA and almost none goes to DHA. For this reason, humans must consume DHA already preformed in seafood, omega-3-rich eggs or fish oil supplements.
HOW DO OMEGA-3s PROTECT AGAINST ALZHEIMER’S DISEASE?
Long-chain omega-3s are protective in several ways. Those in dietary fish oil are anti-inflammatory. They are the source of resolvins and protectins, which are potent anti-inflammatory substances that protect brain cell survival. DHA also decreases the production of beta-amyloid protein, reducing the formation of plaques. DHA is the source of neuroprotectin, a substance involved in brain cell repair and survival that also guards against inflammation and oxidative damage.
Overall, studies of the occurrence of AD in the general population and surveys of foods, especially fish and fish oils, consumed by various populations as well as controlled clinical studies have reported that long-chain omega-3s are beneficial in protecting cognitive function and reducing the likelihood of AD. Some, but not all, studies have reported slower disease progression in patients with mild AD who consumed long-chain omega-3 supplements. Higher plasma DHA concentrations and greater fish consumption were related to a lower chance of developing AD and dementia from all causes. DHA in the blood depends almost exclusively on the amount of DHA in the diet. The caution in these studies is that the consumption of long-chain omega-3s is of most benefit when they are consumed regularly from early adulthood throughout life. Increasing their intake late in life or once symptoms of cognitive decline appear has been of little benefit.
We know that long-chain omega-3s, especially DHA, play a role in the progression of AD. Researchers are investigating how DHA helps improve cognitive function and slows cognitive decline in some patients with mild AD. These mechanisms involve proteins that help prevent plaques and the function of DHA in the regulation of the precursor of beta-amyloid.
DIETARY CHOICES AND ALZHEIMER’S DISEASE
Fortunately, by making some changes in lifestyle, the chance of getting AD may be reduced. Studies so far show the importance of maintaining sufficient regular consumption of seafood or long-chain omega-3s throughout life. What is left to be determined is the effective amount of omega-3s. Although low concentrations of long-chain omega-3s are not consistently observed in AD plasma or brains affected by AD, low fish intake appears to be a consistent factor in the chance of developing dementia. Thus, while the data cannot be considered conclusive, prudent consumers would benefit from eating more fish or taking fish oil capsules. The range of health benefits associated with boosting intakes of long-chain omega-3s is so promising that ensuring an intake of at least 300 to 500 mg per day is widely recommended. In areas of the world where fish and dietary DHA are high, a small dose of supplemental omega-3 may be beneficial. However, in most Western countries, including the U.S., where there is a relative deficiency of dietary DHA, a larger dose may be necessary to show benefits to cognitive function. Although clinical studies have emphasized the importance of DHA in brain health, the anti-inflammatory effects of EPA should not be overlooked. Too little data are available to determine whether both EPA and DHA or mainly DHA are of greatest benefit in maintaining and boosting cognitive function.
*A fully referenced version of this backgrounder is available from the editor.