DHA Protects Against All-Cause Dementia

DHA—You Don’t Have to Eat Fish

DHA Protects Against All-Cause Dementia
Plasma levels of key omega-3 fatty acid from fish oil are
predictive of risk for dementia of any kind
By Hyla Cass, M.D.

ave you been in any good quartiles lately? Don’t worry—it’s not illegal. A quartile is simply one-quarter—the top quarter, next-to-top quarter, next-to-bottom quarter, or bottom quarter—of any group of people who have been ranked according to some measure of interest, such as income, IQ, height, or weight. The term is often used by scientists when they’re ranking people according to some measure of health and well-being (other possible rankings are by tertiles, quintiles, deciles, and plain old halves).

Thus, whether you knew it or not, you are certainly in plenty of different quartiles. The question is, in which top quartiles are you? For starters, you are almost certainly in the top quartile of enlightened nutritional supplement intake, because … well, it’s obvious why. Next, you might ask yourself whether you’re in the top quartile of supplementation with regard to all the major health categories for which your age or general physical condition puts you at significant risk for some degenerative disease. Now let’s see where we’re going with this.

Omega-3s—From Fish or Supplements

You know what the major degenerative diseases of aging are: cardiovascular disease, type 2 diabetes, osteoarthritis, and neurodegenerative diseases, such as Alzheimer’s, which is the most prevalent form (about 70% of all cases) of dementia. In this article we’re concerned about dementia and how to prevent it. In addition to Alzheimer’s, dementia can manifest as the diseases called dementia with Lewy bodies, vascular dementia, dementia of Parkinson’s disease, and many other types. Regardless of the type, the results are pretty much the same—in a word, devastating.

Beyond regular physical exercise (which is highly beneficial for the prevention of almost all degenerative diseases), many kinds of nutrients appear to help prevent dementia. Among them are: the plant alkaloid galantamine (see article on page 11); various antioxidant polyphenols, such as resveratrol (see article on page 4) and quercetin; various herbal products, such as green tea, turmeric, and ginkgo; certain vitamins and minerals; the nitrogenous alcohol choline; and certain fatty acids, notably α-lipoic acid and the omega-3 fatty acids, commonly known as fish oils.

The two most important omega-3s are DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), both of which are derivatives of α-linolenic acid (ALA), an omega-3 found in soybeans, walnuts, wheat germ, and certain plant oils. Unfortunately, our bodies’ conversion of ALA to DHA or EPA is slow and inefficient, so it’s important that we get these nutrients directly from fish or from supplements, which are a more reliable source for maintaining optimal levels on a daily basis.

Brain Food Is Preventive Maintenance

Remember when you used to tell your kids that fish was “brain food”? Well, you were right (it wouldn’t hurt to remind them of that). Scientific research has been confirming what people have known (or at least intuited) about fish for a long time, namely, that eating it helps make us more mentally alert—it enhances memory, attention, and other aspects of cognitive function. (It does not, alas, make us smarter—if only it were that easy!)

Over the long term, remaining more alert is one way of saying that you’re retarding the rate of cognitive decline, a process that afflicts most aging people to one degree or another. If cognitive decline becomes significant enough, it’s called mild cognitive impairment (MCI), a condition for which there are specific diagnostic criteria. Most people with MCI will eventually succumb to Alzheimer’s disease. Even if they’re fortunate enough to avoid that fate, however, they might not escape other forms of dementia. Thus the concept of preventive maintenance applies to your brain as well as to the rest of your body.

Our Brains Are Rich in DHA—Unless They’re Not

Your brain is rich in DHA (it contains much lesser amounts of EPA). DHA levels diminish with age, however, and they’re markedly reduced in the brains (and the blood) of victims of dementia. This suggests that the role of DHA in memory and other cognitive functions is very important.

New evidence for this belief comes from a study just published by a team of American researchers affiliated with the long-running Framingham Heart Study in Framingham, Massachusetts.1 Using data obtained from people enrolled in that study, the researchers investigated whether circulating DHA levels were associated with the risk of developing dementia in general, and Alzheimer’s disease in particular. Thus they looked for DHA in the blood plasma—but not in its free, unbound form. Instead, they measured the levels of DHA incorporated into molecules of phosphatidylcholine (PC), a brain chemical whose molecular structure includes two fatty acids, either or both of which can be DHA. (For more on this subject, see the sidebar.)

Of Fats and Oils and PC Molecules

Omega-3 fatty acids are essential nutrients that must be obtained from food (primarily coldwater fish, such as shad, mackerel, salmon, herring, anchovies, and tuna) or supplements. In our bodies, they can exist in the form of individual (“free”) fatty acids or as components of fats, most of which consist of three fatty acid molecules bound to one molecule of the alcohol glycerol. That’s why the technical name for most fats is triglycerides (there are also diglycerides and monoglycerides, but they’re relatively unimportant). Triglycerides that are solid at room temperature are called fats; those that are liquid at room temperature are called oils.

Fatty acids can exist as components not just of triglycerides but also of phosphoglycerides, which are one of the two major constituents of our cell membranes (the other is cholesterol). Phosphoglycerides are just triglycerides in which one of the three fatty acids has been replaced by a phosphate group to which is attached a nitrogenous alcohol, such as choline. That leaves two fatty acids in the phosphoglyceride, and they can be any of several different kinds, including the omega-3s.

If a phosphoglyceride contains choline as the nitrogenous alcohol, it’s called phosphatidylcholine, and its composition depends on which fatty acids are incorporated in its molecular structure. In our brains, phosphatidylcholine (PC) is the most important phosphoglyceride,* and the most important fatty acid in brain PC is docosahexaenoic acid (DHA). Thus it’s reasonable to suppose that the levels of PC DHA in our blood plasma could serve as an indicator of our brain health, as the study discussed in the article has indeed demonstrated.

*The other three important phosphoglycerides in our brains are phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol. They too can incorporate DHA (as well as other fatty acids) in their molecular structures. Phosphoglycerides, by the way, are often referred to as phospholipids, the name of the larger class of compounds to which they all belong.

Why look for DHA incorporated into PC? Because PC is the predominant phospholipid in the cell membranes of our brains’ neurons, and that’s where most of our DHA is found (it’s also abundant in retinal and testicular tissues). It was already known that individuals with significantly impaired cognitive function or dementia had reduced levels of DHA in their plasma as well as in their brains and that increased consumption of fish and DHA protected against cognitive decline and Alzheimer’s disease. The researchers in the new study wanted to see whether plasma DHA levels (measured as PC DHA) in apparently healthy, nondemented individuals had predictive value in this regard.

The Top Quartile of DHA Levels—A Good Place to Be

The answer was yes. Of the 899 people (average age 76) whom they evaluated, for an average period of 9.1 years, 99 developed dementia; of these cases, 71 were Alzheimer’s disease. After adjusting the data to account for a number of potentially confounding factors—age, sex, homocysteine levels, the gene that predisposes to Alzheimer’s, and educational level—the researchers found that those subjects who were in the top quartile of plasma PC DHA levels had a 47% reduced risk for “all-cause dementia,” i.e., dementia of any kind, compared with those in the lower three quartiles.

When 899 individuals were ranked according to their plasma levels of PC DHA (phosphatidylcholine docosahexaenoic acid), the cumulative incidence of all-cause dementia over a 12-year period was lowest in the top quartile (quartile 4). (Adapted from Ref. 1)

When the data were analyzed with respect to Alzheimer’s disease in particular, the risk reduction turned out to be 40%, but this result was not statistically significant, according to the mathematical procedures used for evaluating such things. Clearly, however, the trend was in the same direction.

When adjustments were made for other potentially confounding factors—body mass index, hypertension, diabetes, smoking status, alcohol consumption, and history of stroke—the results did not change appreciably: for those in the top quartile of plasma PC DHA levels, the risk reductions for all-cause dementia and Alzheimer’s disease were 46% and 38%, respectively, compared with those in the lower three quartiles.

When “Fishy” Results Are OK

In a subsample of 488 participants who completed a questionnaire on eating habits, the researchers found that daily DHA intake and the average number of fish meals consumed per week were (not surprisingly) strongly correlated with plasma PC DHA levels, by quartile. They were also predictive of reduced risk, to almost identical degrees as seen above, but the results were statistically significant for neither all-cause dementia nor Alzheimer’s disease.

The authors summarized their findings as follows:

In our study, the correlation between plasma PC DHA content and fish intake was significant, indicating that fish intake is an important source of dietary DHA. Furthermore, subjects with plasma PC DHA levels in the highest quartile were those with the greatest fish consumption. However, fish intake accounted for less than half of the variability in DHA levels. The major fatty acids in fish are DHA and eicosapentaenoic acid [EPA]. We found no relationship of dementia with plasma PC eicosapentaenoic acid level, whereas the association with plasma PC DHA level was significant. This is consistent with earlier data showing high levels of DHA in brain tissue, and the report of low DHA content in the brain of individuals with Alzheimer disease.

EPA Is Especially Beneficial for Heart Health

In an editorial accompanying the paper discussed above, the author commented on the lack of an association between EPA and a reduced risk for dementia.2 She pointed out that this finding jibed with that of a previous study in which dietary intake of DHA, but not EPA, was associated with a lower risk for developing Alzheimer’s disease.3 She also drew attention, however, to the well documented evidence that EPA is particularly beneficial in reducing the risk for cardiac death. A vast body of literature has shown convincingly (even to the FDA) that the omega-3 fatty acids have antiarrhythmic, antithrombotic, and anti-inflammatory properties that provide protection against various aspects of heart disease. They are among your heart’s best friends. (See “Omega-3 Fish Oils Reduce Mortality from All Causes” in the July 2004 issue.)

Don’t Just Sit There—Climb!

Do you realize that you could not have read and understood this article (or done anything else, for that matter) without the DHA that constitutes such an important element of your brain (and your eyes)? DHA contributes not only to the structure of your neurons but also, in various ways, to their function as well, e.g., in facilitating neurotransmission. It even exerts a strong neuroprotective effect when brain tissue is subject to various forms of stress or injury. (See “DHA Protects Your Brain Cells” in the November 2005 issue.)

DHA is especially important for learning and memory in the rapidly developing brains of infants, but we never outgrow our need for it. So if you’re not already a member of that top quartile for DHA intake—and for EPA intake as well—now would be a good time to climb up there. The view is great!


  1. Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PWF, Wolf PA. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 2006;63:1545-50.
  2. Morris MC. Docosahexaenoic acid and Alzheimer disease. Arch Neurol 2006;63:1527-8.
  3. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003;60:940-6.

Dr. Hyla Cass is a nationally recognized expert in integrative medicine, an assistant clinical professor of psychiatry at the UCLA School of Medicine, and the author or coauthor of several popular books, including Natural Highs: Supplements, Nutrition, and Mind-Body Techniques to Help You Feel Good All the Time and 8 Weeks to Vibrant Health: A Woman’s Take-Charge Program to Correct Imbalances, Reclaim Energy, and Restore Well-Being.

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