Medical and public health innovations in the 20th century have resulted in unprecedented increases in longevity. With increased lifespan, however, the prevalence of age-related diseases also has increased. Chief among these illnesses is Alzheimer's disease, by far the most common cause of dementia in late life. Although Alois Alzheimer first identified the disease that bears his name in 1906, little attention was given the disorder until the past two to three decades.
In the 1970s, clinicians and investigators at Washington University began to seek answers. Led by Leonard Berg, MD, a dementia research team eventually obtained funding from the National Institutes of Health (NIH) in 1979 and inaugurated the Memory and Aging Project (MAP). For 26 years, the MAP has supported seminal studies and projects that have expanded the research understanding of Alzheimer's disease and set worldwide standards for its diagnosis and treatment.
These continuing efforts serve as a model of highly productive, collaborative and interdisciplinary science that aims to change the face of Alzheimer's disease from hopeless to hopeful.
The MAP evolved into two major grants that have been continuously funded by the National Institute on Aging of the NIH. The program project, Healthy Aging and Senile Dementia, awarded first in 1984, and then the Alzheimer's Disease Research Center (Knight ADRC), awarded in 1985. A new program project, The Adult Children Study, was funded in 2005 to study biological markers of AD. The Knight ADRC is one of ~30 federally designated Alzheimer's Disease Centers that foster innovative research on Alzheimer's disease.
The volunteer participants in the Knight ADRC's studies, including those who are aging normally as well as those with dementia and their families, have been major contributors to the program. Some dedicated participants first enrolled in 1979 and continue their annual assessments today. Another major factor in the Knight ADRC's success has been the talents and commitment of its investigators and staff.
The year 2005 represented the 20th anniversary of the establishment of the Knight ADRC, which promotes collaborative research at Washington University and beyond. It also provides a productive training environment for students in nursing, social work and medicine, residents in geriatrics, psychiatry and neurology, and postdoctoral fellows. The Knight ADRC supports junior faculty as well as regional, national and international scholars. In the past five years alone (2000-2005), investigators from Turkey, Taiwan, Italy, Brazil, Canada, Chile, China, Croatia, Japan, Singapore, the Philippines, Spain and South Korea have completed visiting fellowships at the Knight ADRC. In that same period, an additional 54 physicians, nurse practitioners and social workers from St. Louis and outstate Missouri have trained at the Knight ADRC.
The Knight ADRC has formed important partnerships within the St. Louis community. For example, the St. Louis Chapter of the National Alzheimer's Association initially was founded in 1981 by Berg and family members of MAP participants. Today, the St. Louis chapter has grown to encompass the entire eastern third of the State of Missouri as well as 14 counties in southwestern Illinois, and it remains as a key partner. The Knight ADRC has teamed with the St. Louis Rams Football Team, the St. Louis Black Repertory Company, the Mound City Medical Forum and the Delta Sigma Theta Sorority to increase awareness of Alzheimer's disease in the African-American community. The Knight ADRC also is very engaged in national and international Alzheimer-related groups.
These efforts and the impressive body of research produced by the Knight ADRC during the last 20 years stand as tribute to its leadership. Following Berg's retirement in 1998, the Knight ADRC was co-directed by Eugene H. Johnson, PhD, Norman J. Stupp Professor of Neurology, and John C. Morris, MD, Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology, and Professor of Pathology and Immunology, Physical Therapy, and Occupational Therapy until 2004 when Morris assumed the title of Knight ADRC director. Morris reports that "the Knight ADRC and its approach to studying dementia have been recognized for very careful clinical characterization of individuals, even those at the very earliest symptomatic stages of the illness. A great deal of data has been obtained as well on a remarkable group of healthy elderly people. We thus have learned a tremendous amount about healthy aging and dementing disease and have been able to challenge the commonly held assumption that mental abilities inevitably decline with age."
The Knight ADRC's diagnostic approach is one of the major achievements of the program. The Clinical Dementia Rating (CDR) was developed here as a tool for staging Alzheimer's disease and has become the standard scale worldwide by which clinicians rate dementia severity. The ability to distinguish the early stages of Alzheimer's disease from healthy aging has been a direct result of the Knight ADRC's use of collateral source interviews in which information provided by an individual's spouse, child, other relative, or friend is incorporated into the assessment.
Despite these advances, however, Alzheimer's disease remains both underdiagnosed and undertreated, according to Morris. As many as 50 percent of all patients with dementia, particularly those in the milder stages of the diseases, are unrecognized. The Knight ADRC recently has initiated a major study to identify methods that detect Alzheimer brain changes that may begin years or even decades before any clinical symptoms appear.
At present, drugs are available that provide modest symptomatic benefit for individuals with Alzheimer's disease. However, by the time the diagnosis is made, substantial and likely irreversible brain damage has occurred. Newer treatments that may modify or even prevent Alzheimer pathology may have optimal benefit when introduced as early as possible, even before symptoms occur. Thus, the Knight ADRC is pursuing both the evaluation of agents that have the potential to directly modify the disease state as well as methods for presymptomatic detection.
"The dual approach may bring the opportunity to actually prevent Alzheimer's disease," says Morris. "This is a tremendously exciting initiative with real promise for the field."
Since the 1980s, the Knight ADRC has been an active study site for treatment trials of anti-dementia drugs. A new clinical trial beginning in 2005 will study antibodies that in animal models help clear some of the Alzheimer brain lesions.
"Although there are no cures for Alzheimer's disease yet, many promising treatments now are being studied," says David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and Head of the Department of Neurology and an Knight ADRC investigator. "If we do not simultaneously develop ways to predict progression of an individual's disease and his or her response to different types of treatment, we will be way behind when therapies finally arrive."
According to Morris, the Knight ADRC is committed to facilitating the development of such treatments and looks forward to the day on which eventually there will be a world without Alzheimer's.
Article by Holly Edmiston Office of Public Affairs, Washington University School of Medicine. Published originally in the Spring 2005 issue of Outlook Magazine . This article is updated periodically to reflect new developments and changes in our structure. Last updated 1/11/06.