ANTIOXIDANTS MAY DECREASE RISK OF ALZHEIMER’S DISEASE

Two population-based studies of antioxidants suggest that a diet rich in foods containing vitamin E may help protect some people against Alzheimer’s disease. Evidence has suggested that oxidative stress may play a key role in the pathogenesis of Alzheimer’s disease, and both studies, found in the June 26 JAMA, investigated the relationship between taking antioxidants in the forms of food and supplements and developing Alzheimer’s disease. It is noteworthy to mention that both studies found that vitamin E in the form of supplements was not associated with a reduction in the risk of Alzheimer’s disease.

Martha Morris, ScD, of the Rush Institute for Healthy Aging at Rush-Presbyterian-St. Luke’s Medical Center, Chicago, led a study of 815 participants from the Chicago Health and Aging Project. Subjects were at least 65 years old and free of dementia at the start of the study. They were followed for an average of 3.9 years. At an average of 1.7 years from their baseline assessment, the subjects completed a modified version of the Harvard food frequency questionnaire, asking them in detail about the kinds and quantities of foods consumed in the previous year. By the end of the study period, 131 participants had developed Alzheimer’s disease.

Researchers examined the relationship between the intake of antioxidants—including dietary and supplemental vitamins E and C, beta carotene, and a multivitamin—and the development of Alzheimer’s disease. The most significant effect was found among people in the top fifth of dietary vitamin E intake (averaging 11.4 IU/d), whose risk of Alzheimer’s disease was 67% lower when compared to people in the group with the lowest vitamin E consumption (averaging 6.2 IU/d). However, this association was found only among patients without the apolipoprotein E (APOE) epsilon4 allele. No significant change in risk of Alzheimer’s disease was found when the investigators examined vitamin E supplements, the other antioxidant supplements, or a general multivitamin.

The Rotterdam Study comprised 5,395 inhabitants of the Netherlands who were at least 55 years of age and free of dementia. Subjects were asked to complete a checklist indicating all foods and drinks they had consumed during the past year. They also answered questions describing their dietary habits, use of supplements, and prescribed diets. A second dietary assessment included an interview with a dietician, who used a semiquantitative food-frequency questionnaire. After a mean follow-up of six years, 146 subjects had developed Alzheimer’s disease. After statistically adjusting for factors such as education, smoking, and body mass index, investigators found that the risk of developing Alzheimer’s disease for those in the highest third of vitamin E consumption (averaging more than 15.5 mg/d) was 43% less than those in the lowest third (averaging less than 10.5 mg/d). In addition, the risk for Alzheimer’s disease in the highest third of vitamin C consumption (averaging more than 133 mg/d) was reduced by 34% when compared with those in the lowest third (averaging less than 95 mg/d). No significant relationship was found between other antioxidants, supplements, or the APOE epsilon4 allele.

Suggested Reading
Morris MC, Evans DA, Bienias JL, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA. 2002;287:3230-3237.

Engelhart MJ, Geerlings MI, Ruitenberg A, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002;287:3223-3229.

NEW DIAGNOSTIC CRITERIA FOR MULTIPLE SCLEROSIS

Multiple sclerosis has traditionally been diagnosed on the basis of clinical evidence of dissemination in time and space, yet the earliest clinical event in most multiple sclerosis patients is a clinically isolated syndrome. Approximately 50% to 70% of patients with clinically isolated syndromes have disseminated lesions on brain magnetic resonance imaging (MRI) characteristic of multiple sclerosis, and the presence of such lesions increases the likelihood of developing clinically definite multiple sclerosis. The International Panel of McDonald and colleagues set new guidelines for the diagnosis of multiple sclerosis. In addition to retaining the clinically based Poser criteria, the McDonald criteria include MRI evidence of dissemination in time and space, which has the potential to make an earlier diagnosis possible, especially in patients with clinically isolated syndromes.

Patients between the ages of 16 and 50 who were diagnosed with a clinically isolated syndrome were recruited to participate in the ongoing study. MRI of the brain was performed within three months of the onset of symptoms and again after three months, one year, and three years, while MRI of the spinal cord was performed at baseline, one year, and three years. Patients also underwent clinical assessment at baseline, three months, one year, and three years. A neuroradiologist, blinded to the clinical diagnosis, reviewed all the images, noting the number of high signal lesions. From these clinical and MRI examinations, the frequency with which patients developed multiple sclerosis was ascertained by the application of both the new McDonald criteria and the Poser criteria for clinically definite multiple sclerosis.

According to a report in the July Annals of Neurology, the validity of the McDonald criteria was assessed by comparison with the standard for multiple sclerosis that was defined as clinically definite with the Poser criteria. The development of multiple sclerosis according to the new MRI criteria after one year had an overall accuracy of 83% for clinically definite multiple sclerosis at three years. Furthermore, the use of the new McDonald criteria more than doubled the rate of diagnosis of multiple sclerosis within a year of presentation with a clinically isolated syndrome.

Suggested Reading
Dalton CM, Brex PA, Miszkiel KA, et al. Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol. 2002;52:47-53.

CHOLESTEROL-LOWERING DRUGS MAY CUT HEART ATTACK AND STROKE RISK

The prescribing of statins to lower blood cholesterol could reduce rates of heart attack and stroke by at least one third. Findings from the Heart Protection Study, published in the July 6 Lancet, have shown that statins reduce the risk of heart attack and stroke in people who have diabetes or arterial disease, or who have previously had a stroke. The study also found substantial benefits even among high-risk patients considered to have normal or low blood cholesterol concentrations.

The Heart Protection Study involved 20,536 adults between the ages 40 and 80 with coronary disease, other occlusive arterial disease, or diabetes. The subjects were randomly selected to receive daily doses of 40 mg simvastatin or placebo for five years. Subjects had routine follow-up checks and blood monitoring at four, eight, and 12 months, then once every six months until the end of the trial. During the first year, the reduction in major vascular events was not significant, but it became highly noticeable during each following year. Death from all causes was reduced from 14.7% (for patients given placebo) to 12.9% (for patients given simvastatin), mainly due to an 18% relative reduction in the coronary death rate among patients assigned simvastatin. In addition, there were reductions of approximately 25% for nonfatal heart attack or coronary death, for nonfatal or fatal stroke, and for coronary or non-coronary revascularization. Simvastatin’s benefits were additional to those of other cardioprotective treatments, such as aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors.

The study also assessed the effects of using antioxidant vitamin supplements in people with high risk of vascular disease. The subjects were randomly allocated either an antioxidant vitamin supplementation or placebo. While the vitamins appeared to be safe for high-risk individuals, vitamin supplementation did not produce any significant reductions in the five-year risk of heart attack, stroke, or cancer.

Suggested Reading
Heart Protection Study Collaborative Group. MRC/BHF Heart protection study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23-33.

Heart Protection Study Collaborative Group. MRC/BHF Heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.

ASPIRIN WITHIN TWO DAYS OF STROKE REDUCES DEATHS

Giving patients aspirin within 48 hours of the onset of an acute ischemic stroke can reduce mortality and severity of stroke, according to a joint scientific statement from the American Stroke Association and the American Academy of Neurology. The study, published in the July issues of Stroke and Neurology, aims to define the roles of antiplatelet agents, such as aspirin, and anticoagulants, such as heparin.

Investigators conducted a literature review, searching for large, prospective, randomized trials. They found evidence from the Chinese Acute Stroke Trial and the International Stroke Trial that giving 160 or 325 mg of aspirin daily within 48 hours of stroke onset offers a “small but statistically significant” decrease in death rates and disability from stroke. Researchers also noted that aspirin reduces the risk of early recurrent stroke when given within 48 hours of stroke onset but at the same time increases the risk of hemorrhagic stroke. Conversely, anticoagulants have not been shown to reduce death or disability when used within 48 hours.

Additionally, the authors reported that subcutaneous heparin should be considered to prevent deep venous thrombosis in some at-risk patients. A randomized, unblinded trial evaluated the effect of 5,000 units of unfractionated calcium heparin administered subcutaneously every eight hours for two weeks in preventing deep venous thrombosis. The study found that there was a statistically significant reduction in deep venous thrombosis (from 73% to 22%). However, researchers also discovered that subcutaneous unfractionated heparin increased the risk of both systemic and central nervous system hemorrhage.

The report should have a threefold effect on clinical practice, said neurologist and lead author Bruce M. Coull, MD. “We would hope that most acute ischemic stroke patients will receive antiplatelet therapy; that for every patient with acute stroke the issue of deep-vein thrombosis is addressed—whether heparin is used or not; and thirdly, that heparin be used sparingly in this setting unless there is a good rationale for using it.”

NR

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