Finding subtle signs that help spot the onset of Alzheimer's

The pathfinding work of John C. Morris, M.D., has given a measure of hope and help to victims of a cruel disease

The clues are often subtle: A 75-year-old former businessman who has always prepared his own income tax return is now turning over this responsibility to an accountant; an 80-year-old grandmother of six is having trouble remembering her friends' names, her children's birthdays and her grandchildren's ages; and during social occasions, an otherwise active 67-year-old increasingly avoids meaningful conversation and instead appears content to sit alone.

A decade ago, such descriptions would have been casually dismissed as normal signs of aging. Today, thanks to research by John C. Morris, M.D., and his colleagues at the School of Medicine's Alzheimer's Disease Research Center (ADRC), physicians know that some deterioration in memory, thinking and behavior -- even in advanced age -- may be symptoms of early Alzheimer's disease.

John C. Morris, M.D., (right) talks with a patient in the Memory and Aging Project.

Morris, the Harvey A. and Dorismae Hacker Friedman Professor of Neurology and co-director of the ADRC, is a highly regarded expert in the early diagnosis of Alzheimer's disease, an incurable disorder that inevitably leads to a loss of mental and physical abilities.

The disease affects 4 million Americans, and those who have it eventually experience severe dementia that includes memory loss and declines in other areas of intellectual functioning, as well as personality and behavior disturbances. As the disease progresses, these changes interfere with the patients' ability to function. They might be disoriented in familiar places or be unable to dress or bathe themselves. They might no longer even recognize their loved ones.

Morris, who received a medical degree from the University of Rochester School of Medicine and Dentistry in 1974, has long been intrigued by how brain function relates to personality, memory and other intellectual abilities, and he initially considered a career in psychiatry. But during his training as a resident in neuropathology at Cleveland Metropolitan General Hospital, he became interested in how particular lesions in the brain are associated with disturbances in behavior and cognition, the attributes of patients with Alzheimer's disease.

When he joined the medical school in 1982 as a postdoctoral fellow in neuropharmacology, the image of a patient with Alzheimer's disease was someone with advanced disease who could no longer care for himself. In 1983, he moved into the neurology department and began to focus his research on the symptoms of early Alzheimer's disease.

"It became clear to me that the disease often was not recognized in its milder stages and that many of the initial memory and intellectual problems were attributed simply to normal aging," Morris said.

His earliest contributions to Alzheimer's disease were to emphasize that any cognitive changes that prevented an individual from carrying out his or her daily routine in the usual way might be a signal of the mildest form of the disease.

"People have heard that the only sure way of diagnosing Alzheimer's disease is to do an autopsy," said Morris, also director of the Memory and Aging Project, which recruits and tests participants in memory and aging studies. "The clinical techniques developed in the Memory and Aging Project, however, can yield diagnostic accuracy during life of 93 to 95 percent."

These diagnostic procedures include clinical assessments by physicians and nurses and relatives' reports of a person's performance of everyday tasks such as shopping, driving and social interactions. They also measure cognitive abilities such as memorization and word fluency.

"John Morris is one of the most highly regarded Alzheimer's disease researchers in the country," said Jeffrey Cummings, M.D., the Augustus Rose Professor of Neurology and director of the Alzheimer's Disease Center at the University of California-Los Angeles. "He has made unique and important contributions to early detection and staging of Alzheimer's disease."

Alzheimer's markers

German neorologist Alois Alzhemier, who first identified the disease that bears his name, viewed the disease's distinctive neurofibrillary tangles in the brain and drew what he saw (above). With modern staining methods and equipment, neurofibrillary tangles look far different.

Another widely quoted study, published in the same journal in 1996, challenged the prevalent view that beta-amyloid plaques accumulate during normal aging as well as in Alzheimer's disease. Comparing autopsy findings from healthy and from very mildly demented people who had been monitored by the Memory and Aging Project for many years, Morris and his colleagues found few or no plaques in healthy subjects. The participants who were just beginning to show signs of dementia had copious plaques in the brain, suggesting that the deposition of beta-amyloid may be a key event in the development of Alzheimer's disease, occurring before marked symptoms.

"Dr. Morris has special expertise in distinguishing very mild Alzheimer's disease from normal aging," said Leonard Berg, M.D., professor emeritus of neurology at the medical school and former director of the Alzheimer's Disease Research Center. "Clinically, early diagnosis is a very important step forward because the sooner a person knows he has Alzheimer's, the more involved he or she can be in understanding the illness and making decisions about the future."

In addition, those patients diagnosed with early Alzheimer's stand to benefit the most from new medications that can control symptoms of the disease and delay its progression. Morris and his University colleagues are extensively involved in evaluating new medications for Alzheimer's. While the drugs cannot cure the disease or restore memory and cognitive abilities to what they were before a patient is diagnosed, they can help patients maintain their current level of intellectual function and memory for six months to a year.

Morris also leads the Memory Diagnostic Center and Alzheimer Treatment Unit at Barnes-Jewish Hospital, which provides multidisciplinary care for patients with dementia. While physicians increasingly employ sophisticated diagnostic tools such as computer-assisted tomography scans, magnetic-resonance imaging and elaborate blood tests to pinpoint disease markers, such state-of-the-art technology is not yet able to detect Alzheimer's disease conclusively.

Experts who specialize in the diagnosis of Alzheimer's continue to rely heavily on in-depth interviews of patients and family members who are familiar with their everyday activities. Through interviews, key features of early Alzheimer's disease such as declines in reasoning, problem solving and memory can be identified and applied to the Washington University Clinical Dementia Rating (CDR), developed almost 20 years ago by Berg and his colleagues at the medical school. The CDR later was modified by Morris and his co-workers.

This assessment scale is recognized throughout the world for its ability to determine the presence and degree of dementia. Because two-thirds or more of the individuals with mild Alzheimer's disease are unaware that they have a deficit, interviews with family members are crucial for gathering information about how a patient is performing in relation to how he or she used to perform.

Clinical skills

In his avocations as well, Morris depends on skills honed by long practice. He enjoys the outdoors, especially hiking and fishing, and went this summer to Philmont Boy Scout Ranch in New Mexico where he and his 14-year-old son, Ted, hiked 75 miles through the Sangre de Christo Mountains. The 11-day adventure was all part of Ted's scouting experience -- on the same trail that Morris had explored in 1962 when he, too, was a 14-year-old scout. Last year the entire Morris family, including his wife, Lucy, and daughters, Carrie, 15, and Mary, 10, hiked the peaks and canyons of Grand Teton National Park in Wyoming.

Morris has covered a lot of ground, both on foot and in the complex study of Alzheimer's disease. He and his colleagues have made tremendous progress in the past decade in understanding this tragic ailment.

"We don't yet have a cure for the disease or a way to prevent it, but given the pace of discovery, I think we will in the next 20 to 30 years," he said. "We continue to be indebted to our patients and their families and the research volunteers -- some of whom have returned annually for the past 20 years. We could not have accomplished so much without them."