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Brain and Nervous System
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Thinking Disorders

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Dietary Antioxidants May Decrease Risk of Alzheimer's Disease

Alzheimer’s disease (AD) is a complex disease that spreads through the brain. It affects some 4 million Americans, causing memory loss, impaired thinking, and changes in personality. Scientists have suspected that substances called antioxidants — vitamin C, vitamin E, and beta carotene, for example — may guard against AD. However, studies testing the relationship between antioxidant supplements and the risk of AD have not found consistent evidence of a benefit. But now two studies published in the Journal of the American Medical Association have found that high intakes of antioxidants from food may reduce the risk of developing AD.

In the first study, researchers recruited 5,395 participants with an average age of 67.7 years, who lived independently. All participants reported their eating habits and went through two mental state examinations to ensure that they were free of dementia at the start of the study.
During six years of follow-up, the researchers re-screened the participants for Alzheimer’s disease. They found that high dietary intake of vitamin C significantly reduced the risk of developing Alzheimer’s disease and that the reduced risk of AD from high dietary intake of vitamin E was also borderline significant. These antioxidants were most effective at preventing AD in current smokers, compared with current non-smokers.

Use of dietary supplements was controlled in this study, so the beneficial effects of vitamins C and E were only from food. Vitamin C is found in large amounts in citrus fruits, kiwi, and broccoli, and good sources of vitamin E include nuts, milk, and egg yolk.

In the second study, participants were also free of Alzheimer’s disease at the beginning and completed a food frequency questionnaire. The questionnaire helped researchers keep track of the intake of certain foods and supplements. The 815 subjects were 65 years and older, and were followed for four years.

After adjusting for age, education, sex, race, and presence of APOE e4 (a genetic characteristic that makes a person more likely to develop AD), the researchers found that those with the highest dietary intake of vitamin E were 70% less likely to develop AD than those with the lowest dietary intake of vitamin E. However, the highest Vitamin E intake for the study was 363.6 International Units (IU) per day, well above the Recommended Dietary Allowance of 22 IU.

The other dietary antioxidants tested in this study, vitamin C and beta carotene, did not reduce the risk of AD. More research will need to be performed to find out why vitamin C proved effective in one study but not in the other. While dietary antioxidants are proving more effective in reducing Alzheimer's risk than antioxidant supplements, these weren't randomized, clinical trials, so these studies won't translate into dietary recommendations.

August 2002 Update

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On-Pump and Off-Pump Coronary Bypass Surgeries Have Similar Cognitive Outcomes

Coronary artery bypass graft (CABG) surgery is performed to bypass blood around clogged arteries and improve the flow of blood and oxygen to the heart. But while these surgeries help the heart, they may be harming the brain. A study published in 2000 suggested that 23% of patients suffer from cognitive decline two months after CABG surgery.

The cardiopulmonary bypass, or "on-pump" procedure, has often been blamed for this decline, in part because it generates tiny clots that may affect cognitive function. Recent advances have allowed for CABG surgery to be performed on a beating heart ("off-pump" CABG). A study in the Journal of the American Medical Association examined whether off-pump CABG surgery results in a lower incidence of cognitive decline than on-pump CABG surgery.

Researchers from the Octopus Study Group (named for an off-pump procedure called the Octopus method) randomly assigned 281 patients scheduled for their first CABG surgery to either an on-pump or off-pump procedure. They then administered neuropsychological tests to the patients one day before surgery and then 3 and 12 months after surgery. The tests assessed major areas of cognitive function including verbal memory; visuospatial and motor capacity; selective, sustained, and divided attention; working memory; and information processing. Cognitive decline was defined as a 20% decrease in performance from the baseline score in at least 3 of the areas tested.

At three months after surgery, cognitive decline was found to be 35% more likely after on-pump surgery; it occurred in 29.2% of patients who had the on-pump surgery, compared to 21.1% of patients who had the off-pump procedure. At twelve months, however, the differences in cognitive decline between the two groups were no longer statistically significant — 33.6% of patients who had on-pump surgery compared to 30.8% of patients who had off-pump surgery.

The difference in cognitive decline of off-pump versus on-pump surgery was smaller than expected, and the researchers speculated that factors other than the cardiopulmonary bypass might be responsible for the cognitive decline. They proposed that general surgical trauma may be to blame, or that the off-pump technique itself may be a new source of cognitive decline. They also noted that the mean age of patients in this study (61 years) was younger than the average age (66 years) of patients who have had CABG surgery in the past decade. The off-pump technique may have additional benefits for older patients with more advanced coronary artery disease and who often suffer from additional, unrelated medical conditions.

May 2001 Update

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Statins Associated With Lower Dementia Risk

Most people who develop dementia - poor memory and intellectual functioning that often accompanies old age - have Alzheimer's disease. But a small, yet sizable group of people appear to develop dementia from a narrowing of the arteries supplying the brain. The lack of blood can lead to many small areas of damage to the brain; each too small to be noticeable as a "stroke," but collectively devastating in their effect. This syndrome is called "vascular dementia" to differentiate it from Alzheimer's disease and other types of dementia.

Presumably because high cholesterol levels contribute to the damage of brain's blood vessels, researchers have looked for evidence that people who use statins might have a lower rate of dementia. Statins are the most widely used cholesterol-lowering drugs. In addition to protecting the brain's arteries from atherosclerosis, some scientists believe statins may also help protect the brain against non-vascular forms of dementia, including Alzheimer's disease.

A recent study examined the relationship between statin use and types of dementia among people living in the United Kingdom. The researchers identified 284 people with dementia, and matched them with 1,080 "control" subjects of similar age and sex, but without dementia. After adjusting statistically for a wide range of clinical information, the researchers found statin use was associated with a 71% reduction in dementia risk.

Could statins really cut the risk for dementia by two-thirds or more? It seems unlikely, since other studies haven't suggested protective effects of this size. On the other hand, this study adds to several other laboratory and epidemiological investigations that suggest statins might provide some benefit in the protecting the brain - if for no other reason than lower cholesterol levels lead to healthier brain arteries. No one should start taking statins as a strategy for preventing dementia, but these data do provide another reason for people with elevated cholesterol levels who are on these medications to be sure they take them as prescribed.
October 2001 Update

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Early Cognitive Impairment Following Coronary Bypass May Predict Lasting Cognitive Impairment

More than 500,000 coronary-artery bypass grafting (CABG) surgical procedures are performed in the United States each year to bypass blood around clogged arteries and improve the flow of blood and oxygen to the heart. Advances in anesthesia, surgical procedure, and other areas have made CABG a relatively safe procedure for an expanding group of heart disease patients including older and other high-risk patients. But while the risk of death after CABG has decreased, the risk of cognitive impairment has not. Growing evidence suggests that many patients experience short-term cognitive impairment after CABG.

A recent study in the New England Journal of Medicine confirmed not only the high incidence but also the persistence of cognitive decline following the procedure. It also showed that patients who exhibit signs of cognitive decline immediately following surgery are more likely to continue to suffer from cognitive decline at up to five years after surgery. Researchers from Duke University Medical Center tested the cognitive function of 261 patients before they underwent CABG surgery, and then again before discharge from the hospital and at six weeks, six months, and five years after the CABG procedure. 172 patients, whose average age was 61, completed all of the follow-up.

The researchers found that the incidence of cognitive decline was 53% at discharge, 36% at six weeks, 24% at six months, and 42% at five years. The pattern demonstrated improvement of cognitive functioning within the first six months, and then a decline between six months and five years after surgery.

Even after controlling for age, education level, and baseline test score, patients who experienced cognitive decline immediately following surgery were at a significantly increased risk for long-term cognitive decline and a reduced level of overall cognitive functioning.

It remains unclear why early, postsurgical cognitive decline is associated with a greater risk of long-term cognitive decline.
April 2001 Update

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Estrogen Replacement Therapy Found Not Effective for Mild to Moderate Alzheimer's Disease

Several small, short-term clinical trials have indicated that estrogen may slow or halt the progression of Alzheimer's disease in women, and many animal studies have suggested mechanisms by which the hormone may accomplish this.

However, in the largest and longest clinical trial of its kind to date, researchers found that estrogen did not slow or stop cognitive decline, or improve mood, in women with Alzheimer's disease.

In the randomized, double-blind study, published in the February 23, 2000, Journal of the American Medical Association, researchers assigned study participants to receive either a placebo, or a daily dose of either 0.625 mg or 1.25 mg of estrogen. All 120 participants were women with an average age of 75 years who had mild to moderate Alzheimer's. After one year of treatment, women receiving high- or low-dose estrogen replacement therapy did not have any cognitive or functional improvements compared to the women who took a placebo. The researchers concluded that estrogen should not be used to treat women with established Alzheimer's disease.

Though the results of this study are disappointing, the potential for estrogen to prevent or delay the onset of Alzheimer's disease still exists and is being investigated in several large-scale studies including the Women's Health Initiative Memory Study and the Women's International Study of Long Duration Oestrogen After Menopause.

For more information on Alzheimer's disease, see page 363 of the Harvard Medical School Family Health Guide. To learn more about estrogen replacement therapy, see page 1049 of the Harvard Medical School Family Health Guide.

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Reduce High Blood Pressure, Reduce the Risk of Dementia

High systolic blood pressures (when the top blood pressure number is above normal) in elderly people increases the chances that they will develop the diminished mental capacity known as dementia. Certainly this makes sense. High blood pressure damages blood vessels. When the blood supply to the brain is compromised, there may be damage to the brain tissue. Sometimes this damage is very abrupt, such as in the loss of function that may accompany a stroke. Other times, the damage is recognized gradually, as a person slowly loses some mental capabilities. This is the case with vascular dementia.

A major European study tested the theory that treating high blood pressure might reduce the incidence of dementia in elderly people. One-hundred-six centers in 19 countries enrolled 3,162 patients in this trial. Investigators randomly assigned these patients to receive either medicine to help lower blood pressure or a placebo and then followed the health of these individuals for two years. The results were so compelling that the study was stopped early. In this study, treatment of high systolic blood pressure reduced the incidence of dementia by 50%. Put another way, treating 1,000 patients with high blood pressure, over five years, could prevent 19 cases of dementia.

Researchers are just beginning to understand the physiology of dementia and how we might slow or prevent this process. Controlling high blood pressure is an important part of staying healthy for many reasons, for mind as well as body. For more information on dementia, see page 362 in the Family Health Guide.

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©2000–2006 President & Fellows of Harvard College
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