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March / April 2003

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Losing Your Edge

Illustration by Michael Mardosa

Losing Your Edge
UMaine study highlights the health risks that result in reduced mental function

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In a conversation, forgetting a familiar name or fact can generate a chagrined smile and a chuckle or frustration and concern. For most people, sporadic memory lapses are no more significant than a trip to the grocery store. We all forget things during the course of the day. But for others, more frequent memory lapses can be a symptom of something less benign.

Exactly how physical health affects mental functioning has been the subject of one of the longest-running research projects at the University of Maine the Maine-Syracuse Studies of Hypertension and Cognitive Functioning. Founded in 1974 by Merrill "Pete" Elias, UMaine professor of psychology and epidemiology, and David Streeten of the State University of New York at Syracuse, the project has demonstrated an important correlation between mental and physical health: Two age-related health problems untreated high blood pressure and diabetes contribute to reductions in mental skills as we age.

The Maine-Syracuse Studies have been supported continuously by the National Institutes of Health (NIH), including most recently the National Heart, Lung and Blood Institute. The data collected by Elias, UMaine psychologist Michael Robbins and their colleagues provides a perspective on the long, slow slide from alert mental functioning that occurs as some people age.

In separate research with colleagues at Boston University, Elias also has shown that some changes in mental functioning can even signal the onset of Alzheimer's Disease, the most common form of dementia in the elderly.

Now, Elias, Robbins and other UMaine scientists are expanding their ongoing study of cognitive functioning. They are investigating a gene and a naturally occurring chemical in the body that may be associated with dementia, particularly Alzheimer's. They are focusing on what happens before the onset of major symptoms before friends and family members notice that a loved one seems to be increasingly confused and forgetful.

Their findings may help scientists find treatments for mild reductions in mental skills reductions that can be critical for people in high-risk professions as well as the more debilitating conditions that rob people of their memories and their quality of life. Their study underscores the need for people to seek treatment for high blood pressure, diabetes and obesity, factors that make reduced mental function more likely. As yet, there is no medication that directly restores or maintains mental function, although pharmaceutical companies are conducting trials.

As the median age of America's population rises, early detection and treatment of these conditions are becoming more critical. According to the Centers for Disease Control and Prevention, more Americans are now killed annually by Alzheimer's than by traffic accidents. An estimated 4 million Americans are thought to suffer from the disease; almost twice that many have some form of dementia. The number of the most vulnerable Americans, people over 85 years old, is expected to double by 2030.

The Maine-Syracuse project tracks the health and mental functioning of about 2,000 people in New York state and Maine. Some have moved to other states but continue to participate in regular checkups and tests.

Every five years, the participants fill out detailed questionnaires on their diet and health, and undergo physical examinations and clinical tests when necessary. They complete an extensive series of rigorous cognitive tests of reasoning, and verbal, visual and memory skills. Each session takes more than three hours.

The data from 28 years of study clearly links high blood pressure and diabetes with a modest decline in mental functioning, says Elias. "We're not talking about stupid or smart. We're talking about individual changes in cognitive ability as a result of experiencing one of these risk factors over a period of time," says Elias. "Hypertension and diabetes have insidious effects on cognitive functioning. If untreated, they eventually erode your ability to think and remember."

The new emphasis on factors related to dementia and Alzheimer's is the result of a five-year, $2.3 million NIH grant. The goal is to study a gene known as APOE4 and homocysteine, a chemical that is produced naturally by the body.

The UMaine research team includes Penelope Elias, a Boston University psychologist who also holds a part-time position at UMaine; and Judith Deking and Suzanne Brennan, scientific and medical technicians, respectively, at Syracuse. Dr. Steven Scheinman of the State University of New York Upstate Medical University in Syracuse conducts the blood work and APOE4 genotyping.

Marc Budge, a geriatric physician at Oxford University in England, collaborates on the homocysteine analyses. Budge also works with the Oxford Project to Investigate Memory and Aging, which has conducted major studies of homocysteine, APOE4 and Alzheimer's.

The Maine-Syracuse project is unusual because it has followed the same individuals for so long, notes Pete Elias. Such a longitudinal study generates a picture of how people change over time. It may be the only study in the country that has tracked changes in cognitive function in relation to blood pressure status over such a long period for people with normal mental skills, he says.

Only now are some of those people starting to show signs of dementia. An important question, says Elias, is why a small portion of individuals develop dementia, while others show cognitive change over time but remain free of the disease.

"Once dementia is diagnosed, the risk factors and cognitive function become intertwined," says Elias. "The cause becomes more difficult to pinpoint. For example, is high blood pressure contributing to Alzheimer's or is it caused by Alzheimer's?" The same problem occurs with people who suffer from vascular dementia, which can be caused by visible strokes, as well as undiagnosed or so-called "silent strokes."

Evidence that a reduction in mental functioning might signal the eventual onset of dementia first came as a result of Elias' collaboration with the well-known Framingham Heart Study in Massachusetts. Boston University, where he holds an appointment, is a center of Framingham data analysis.

When the Framingham project began in the 1950s, physicians did little to treat high blood pressure. In fact, it was thought to be important to sustain blood circulation in the brain. It wasn't until the 1960s, when Framingham data started getting attention, that high blood pressure was understood to be a serious risk for heart disease and stroke.

In the mid-1970s, about a third of the 5,000 Framingham participants took a short but comprehensive battery of mental skills tests. In analyzing the results, Pete Elias found that individuals who performed poorly on those tests had higher blood pressure, despite many controls for treatment, age, education, occupation and other variables. Eventually, he and other Framingham scientists concluded that those with lower scores on the mental skills tests also had a higher risk of developing probable Alzheimer's.

The changes in mental functioning detected by the cognitive skills tests can precede a diagnosis of probable Alzheimer's by at least 10 years, they reported.

In the last few years, scientists have unraveled twists and turns in the chemical path that leads from normal brain function to Alzheimer's. They also understand that the brain lesions caused by strokes are a significant cause of dementia. However, it's still not clear what enables some people to stay sharp well into their 90s while mental confusion begins to rob others of their memories and reasoning abilities at a much younger age.

The APOE4 gene and elevated levels of homocysteine, says Elias, are now thought to be two of multiple factors that may predispose people to a higher risk of reduced mental skills or dementia.

"One of the things we're interested in is the impact of these cumulative hits," he says. "Say you have high blood pressure, high cholesterol, diabetes and the APOE4 gene, but I have only one of those factors. What's your risk of lower cognitive performance relative to mine?"

Over the past year, Elias and his team have been re-testing the Maine-Syracuse Studies participants and collecting more health data. Blood samples are being analyzed for both the APOE4 gene and homocysteine levels.

"High blood pressure, obesity, high homocysteine and other risk factors increase the likelihood of mental decline," says Elias, "but they don't mean that you will necessarily decline. Consequently, treatment and prevention are important. Intervention in the process of mental decline is possible."

The Maine-Syracuse data and other studies do show, in fact, that for some people, bringing blood pressure down from very high levels can improve mental skills. "The first line of defense is reducing long-term risk," says Elias. "If you cut your fat and sugar intake, you would be addressing the prevention end of the equation. But there is evidence that treatment for high blood pressure and diabetes can improve cognition. It depends on the severity of those risk factors and how many of them you have."

Treatments for high blood pressure and cardiovascular disease have multiplied in recent years, but many of those at risk are neither diagnosed nor successfully treated, Elias notes. "People take losses of cognitive functioning, even minor losses, very seriously, which is a reasonable concern in this competitive society. Thus, physicians can offer yet another incentive for adherence to prescriptions for prevention and treatment: reduce risk factors to preserve the highest possible mental function over the life span."

by Nick Houtman
March-April, 2003

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