William Markesbery, the University of Kentucky's patriarch of Alzheimer's disease research and director of the UK Alzheimer's Disease Research Center (ADRC), believes the key to Alzheimer's disease is prevention. He also believes that vitamin E is an important part of this key. And though he is an uncommonly soft-spoken man, he wants his E-message to get out loud and clear.
"So far, vitamin E has emerged as one of the weapons we have against dementia," Markesbery says from his office in the Sanders-Brown Center on Aging, where he has served as director since 1979. "There are several other things you can do to lower your risk of getting Alzheimer's, but vitamin E taken in conjunction with vitamin C is importanta previous study showed that vitamin E is one factor that slows, slightly, the progression of the disease. The important thing for individuals at risk is to take vitamin E and vitamin C along with folic acid prior to getting the disease."
William Markesbery, with help from Ann Tudor in the Sanders-Brown Center on Aging, examines brain tissue from a patient with probable Alzheimer's disease. Markesbery has been researching the causes of dementia for over 30 years at UK.
So what are these risk factors?
A major factor is age: The risk of developing Alzheimer's increases with age. One out of every 10 persons 65 years and older is a victim of Alzheimer's disease, although some victims may be in their 40s and 50s. Approximately 20 percent of Americans between the ages of 75 and 84, and almost half of those 85 years and older suffer from Alzheimer's disease.
Other risk factors under study are traumatic head injury, low education attainment, early low linguistic skills, high-fat and high-caloric intake, and genetics. What scientists are now calling "incipient" Alzheimer'sthe earliest onset of the disease regardless of agehas been clearly shown to be genetic in origin. Three genes, Markesbery explains, account for less than 2 percent of cases of those with early-onset Alzheimer's disease.
People in all of these at-risk categories may benefit from a study Markesbery is currently heading up. Funded by a $5 million grant from the National Institute on Aging, the study will pair vitamin E with selenium, an essential trace element found in all cells and tissues in the body. Selenium is found in water and foodseafood, meats and Brazil nuts, for example. Vitamin E is found in a wide range of foods, especially vegetables, vegetable oils, nuts, and egg yolks.
There is prior evidence that enhanced levels of selenium in the brain might increase antioxidant defense mechanisms against Alzheimer's disease. Taken together, Markesbery says, these two natural antioxidant supplements might work better than alone in fighting oxidative stress.
"What is oxidative stress?" Markesbery asks rhetorically. "Well, we obviously need oxygen to live, but the reactions that oxygen undergoes in the body have to be carefully controlled or else your body begins to produce oxygen radicals that damage lipids, proteins and DNA in cells, especially neurons."
This current project, which is called PREADVISE (Prevention of Alzheimer's Disease by Vitamin E and Selenium), will link up with SELECT (Selenium and Vitamin E Cancer Prevention Trial), a large National Cancer Institute-sponsored study looking at the effects of these two substances in preventing prostate cancer.
The five-year PREADVISE study will examine a subgroup of about 10,000 of the more than 32,000 men being recruited nationally for SELECT.
"Like prostate cancer, Alzheimer's disease usually occurs later in life, so this study presents a unique opportunity to assess the impact of selenium and vitamin E on the beginnings of dementia," Markesbery says.
So far, more than 400 locations in the United States, Canada and Puerto Rico have enrolled men in SELECT. Study investigators hope to recruit all the participants during the first five years of the trial, so each man can be followed for at least seven years. Five study sites are located in Kentucky, including Central Baptist Hospital in Lexington and the UK Markey Cancer Center.
Men may qualify to participate in this study if they are age 62 or older (60 or older if of Hispanic or African origin) and in general good health. Participants must also have no history of diagnosed dementia and no major head injury in the last two years.
"Prospective participants take a mental status examination, and they have to score in the normal range on that," Markesbery explains. "And there's an intake assessment where they're asked a lot of questions, especially about their family history." Participants are then placed randomly into one of four groups: They get either vitamin E or selenium, vitamin E and selenium, or a placebo.
"We're in the very early stages of this 12-year-long trial," says Maresbery, "and the key right now is active recruiting. Obviously the assessment of all the data we get won't occur for some time, but we will get updates along the way on how we're doing."
The PREADVISE study is one example, he says, of how basic laboratory data from many Sanders-Brown studies is being translated to preventive studies in Alzheimer's disease. "You just can't overstate the importance of prevention. This disease starts many years before it ever shows up clinically."
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For more information about Alzheimer's disease clinical trials at the UK Sanders-Brown Center on Aging, call 859/323-6729 or visit www.mc.uky.edu/coa.