DIMENSIONS Summer 2002

Spotlight on Research: ADRC Investigators at the VA Tackle the Mysteries of Alzheimer's Disease From Many Angles

by Cheryl Dawes

photo of ADRC investigators at the VA

Scientific and clinical labs at the Seattle VA Medical Center are abuzz with research focused on Alzheimer's disease (AD) and related dementias. ADRC investigators housed there delve into a broad array of research projects aimed at unlocking the mysteries of AD. Some projects focus on better understanding how AD develops and progresses, some seek to illuminate risk factors for developing AD, and others test new interventions designed to slow or stop the progression of this debilitating disease.

"Two-thirds of the University of Washington ADRC is physically located at the VA," says Dr. Elaine Peskind, professor of psychiatry and behavioral sciences and new associate director of the ADRC. "We have wonderful lab space and facilities for working with patients-the ADRC clinical core is located here."

Clinical research is a key to understanding AD. Clinical research programs rely on individuals from the community, with and without memory problems, who volunteer as study participants. "Although we are at the VA, our programs are open to everyone. Very few of our patients are actually veterans," says Peskind.

Peskind conducts research exploring the relationship of hormones released in the blood in response to stress, genetic history and memory loss. Her current study includes adults ranging in age from 21 to 85 with and without memory loss. It involves studying stress response and memory in individuals with different versions of the apolipoprotien (APOE) gene, which has been identified as a risk factor for AD. Results of this study of how genetics and stress hormones affect memory could lead to interventions that decrease the risk for AD or slow its progression.

Peskind also leads clinical trials of investigational drugs that may benefit patients with AD. These clinical trials are "double-blind, placebo-controlled" studies. In a double-blind study, neither the participant nor the investigator knows who is getting the active medication and who is getting a placebo pill (a pill that looks the same but has no active ingredients in it). Study participants are randomly assigned to either the group that receives the active medication or the group that receives the placebo. The use of a placebo group helps to insure that the observed effect is due to the treatment and not to other extraneous factors.

One such study is investigating the safety and efficacy of an investigational medication called memantine, for treating mild to moderate AD. This ongoing study is enrolling patients with AD who are living at home with a caregiver and who are not taking other drugs used to treat dementia. Individuals who have not been helped by one of the currently marketed medications for the treatment of AD, or who had side effects to one of these currently available medications, may be interested in participating in this study.

ADRC investigators, Drs. Thomas Bird, Gerard Schellen-berg and Ellen Wijsman conduct research on the role of genetics in AD. They work to identify genes responsible for both early-onset and late-onset AD. Their program is also investigating genetic factors in fronto-temporal dementia, which is similar to AD and sometimes called Pick's disease. The researchers are seeking families to participate in these studies with three or more members (living or deceased) who have had Alzheimer's disease or other types of dementia. Participants are interviewed about family history over the phone and may undergo clinical evaluation.

Drs. Debby Tsuang and Jim Leverenz, also ADRC investigators at the VA, are studying dementia with Lewy bodies-a form of dementia that is related to, but distinct from AD. "The available data suggest that there are some differences in clinical course and management of these patients, compared to patients with Alz-heimer's disease alone," explains Tsuang. "So, it is important to try to make that distinction while an individual is seeking a diagnosis and exploring treatment options."

Because Lewy bodies in the brain can only be identified in an autopsy, Tsuang and Leverenz are seeking to determine the best clinical predictors of dementia with Lewy bodies. To do so, they are examining clinical information from individuals who were followed in AD research studies over the past 20 years and are now deceased. By comparing these individuals' symptoms with their brain tissue, Tsuang and Leverenz hope to determine what kinds of symptoms are associated with the presence of Lewy bodies. Tsuang and Leverenz are also recruiting subjects who have family members who may have dementia with Lewy bodies, as well as individuals from the ADRC participant registry who have a diagnosis of dementia with Lewy bodies.

For general information about participating in ADRC studies at the VA and enrolling in the ADRC participant registry, contact Beth Hutchings by phone at 206-764-2069. For information about genetic studies, contact Ellen Steinbart at 206-764-2112. Contact Andrea Busby at 206-277-1037 for information about the study of genetics, stress hormones and memory.

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