The University Record, March 19, 2001

Gilman discusses Alzheimer’s disease research in Henry Russel Lecture

By Mary Jo Frank
Office of the Vice President for Communications

Debunking the common but mistaken belief that senility is a natural part of the aging process and untreatable, Sid Gilman, the William J. Herdman Professor of Neurology, says neurological diseases that cause dementia—including Alzheimer’s disease—can be and are being treated. Alzheimer’s disease is one of only 70 causes of dementia. About 30 percent of those causes can be cured, he says.

In his March 13 Henry Russel Lecture in Rackham Auditorium, the director of the Michigan Alzheimer’s Disease Research Center said clinical trials already are under way and more are planned using vaccines and new treatments based on research with transgenic animal models.

In the meantime, the debilitating effects of Alzheimer’s disease can be delayed with behavior modification; nonsteroidal anti-inflammatory medications; psychotropic agents such as anti-depressants, anti-psychotics and sedatives; anti-oxidants such as vitamins E and C; and estrogen replacement therapy (when started at the onset of menopause). Cholinesterase inhibitors, such as Aricept, Exelon and Reminyl, also may improve intellectual functioning in Alzheimer’s disease patients, said Gilman, chair of the Department of Neurology and a pioneer in the use of positron emission tomography to assess biochemical changes of the brain in movement disorders and dementia.

The Henry Russel Lectureship, awarded annually since 1925, is the highest honor the University can confer upon a senior faculty member and is given for distinguished achievement in research and teaching. Tropical ecologist Lisa M. Curran, assistant professor of ecology and environmental biology, also was honored at the lecture. She received the Henry Russel Award, which is given to an assistant or associate professor selected for excellence in teaching and the promise of distinction in scholarship.

In his lecture about past and present research on Alzheimer’s disease, Gilman explained it is a progressive neurological dementia characterized by loss of cognition and, in the brain, three characteristic changes consisting of loss of large numbers of neurons (nerve cells), neurofibrillary tangles affecting large numbers of the remaining neurons and the deposition of neuritic plaques, which are composed of beta amyloid protein.

Bavarian-born psychiatrist Alois Alzheimer first described the disease and resulting changes in the brain in 1907 in a 51-year-old woman, who suffered increasing memory impairments, became lost in her own home, thought people wanted to kill her, suffered delirium and incontinence, and died within five years of the onset of symptoms.

Alzheimer examined under the microscope multiple histological sections of the patient’s brain that had been stained with a silver-containing dye. He described the three characteristic changes now known to occur in Alzheimer’s disease. Large numbers of neurons had totally disappeared, and many of the neurons that remained had tangles of neurofibrils covering their surface. Also, there were large numbers of neuritic plaques distributed throughout the cerebral cortex.

Gilman illustrated his lecture with colorful slides showing brain activity demonstrated by positron emission tomography in normal brains and the brains of patients with Alzheimer’s disease. Alzheimer’s usually strikes between the ages of 40 and 90 but has been found in individuals in their 30s. It mainly affects the elderly. While only 3 percent of people 65–74 are diagnosed with Alzheimer’s, the percentage increases dramatically with age. Forty-seven percent of people 85 and older have Alzheimer’s disease, he said. Currently, about 4 million Americans are 85 or older. That number is expected to climb to 8 million by 2030, Gilman said. The economic and social costs are enormous. In 1998, it cost, on average, $47,000 a year to care for a patient with Alzheimer’s disease.

When Alzheimer’s disease is suspected, Gilman said, it is important to make sure the patient is not suffering from another malady such as depression, which is treatable and curable. Scientists focus on important biomarkers such as blood and cerebrospinal fluid and imaging of the brain to determine the severity and location of the disease, Gilman explained, and to monitor efficacy of treatment.

Major risk factors for Alzheimer’s disease, Gilman said, are age, genetic influences and whether the person has Down’s syndrome. In late-onset Alzheimer’s—more than 95 percent of all cases—there is a strong genetic influence. A person who has one close, affected relative—parent or sibling—has a four times greater risk of having Alzheimer’s than the rest of the population. A person who has two first-degree relatives with Alzheimer’s has a 40-fold chance of getting the disease. Down’s syndrome patients also are at high risk for Alzheimer’s disease.

Other risk factors include:

  • Being a woman.

  • History of head injury involving at least 30 minutes of unconsciousness.

  • Level of education or intellectual or mental activity.

    Although it is not clear whether a higher intellect or level of mental activity protects one from Alzheimer’s disease, Gilman said, a study of nuns in Minneapolis showed that frequency of dementia was highest among those with low idea density and low grammatical complexity in entrance essays they wrote at age 18.

    High cholesterol and smoking cigarettes also may increase risk, Gilman said.

    As for future treatments, Gilman said, academic researchers and pharmaceutical companies are working on vaccinations to prevent loss of neurons and plaque buildup in the brain. Estrogen replacement, cholesterol-lowering medications and nerve-growth factors may help. Trials also are being conducted using anti-oxidants.

    Gilman peppered his lecture with humor, including a story about two women who found a small green frog in a park. The frog explained that he was a neurologist who had been transformed by a spell and only needed to be kissed for the spell to be broken. One woman scooped up the frog and continued walking. The other asked why she didn’t kiss it. With the frog firmly in her pocket, the woman responded, “A talking frog is worth a lot more than a neurologist.”

    The once commonly held belief that neurologists could diagnose but do nothing to treat patients is simply no longer true, Gilman said.