DIMENSIONS Autumn 1999


by Julie Cleveland

On September 9, the UW Alzheimer's Disease Research Center sponsored a Public Forum to inform our community about the latest research advances in AD. Over 300 friends, family members and professionals interested in learning about AD attended. The response of attendees was very positive, with most seeing the forum as an educational and interesting way to obtain more information on AD. Four speakers from the ADRC presented the latest in genetics, pharmacotherapy, caregiver support and patient care, and cross-cultural issues.

"Is Alzheimer's Disease Inherited?: Updates on What We Know about Genetics of AD," Thomas Bird, MD
Alzheimer's disease afflicts approximately four million people in the U.S. Although there is no specific test for Alzheimer's disease, the accuracy of clinical diagnosis is about 80 to 90 percent. The clinical syndrome of AD is memory loss, plus other cognitive and behavioral changes. The pathological features include shrinkage of the brain caused by loss of neurons, and the presence of amyloid plaques and neurofibrillary tangles, both of which are accumulations of abnormal proteins in the brain.

There are at least two major forms of AD: familial AD and sporadic AD. Early-onset familial AD is a rare, inherited form and accounts for only 2-3 percent of AD cases. One gene associated with this form of dementia is the amyloid precursor protein (APP) gene on chromosome 21. Mutations to this gene can result in AD that starts between 45 and 60 years of age. The two other genes associated with early onset dementia are the presenilin 1 (PCS 1 ) and presenilin 2 (PS2) genes on chromosomes 14 and 1, respectively.

The majority of people with AD have the late-onset sporadic form. The apolipoprotein-E gene (APOE) has been identified as a susceptibility gene for this form of AD. There are three common variations or alleles of APOE among the general population and one of them - the E4 allele - has been shown to increase the risk for AD.

"What Treatments Are on the Horizon?: Current and Anticipated Medications for AD," Elaine Peskind, MD
There are three major areas of pharmacological treatment for cognitive disturbance in AD: 1) cholinergic enhancement strategies, 2) antioxidants, and 3) other experimental approaches.

Cholinergic enhancement strategies include cholinesterase inhibitors, such as tacrine (Cognex), and donepezil (Aricept), and M1 muscarinic cholinergic antagonists (which are currently in development). Cholinesterase inhibitors represent the only pharmacological therapy currently approved for the treatment of AD. These drugs increase the availability of acetylcholine in the brain and have been found to be modestly effective for improving cognitive function (memory, language, praxis) in AD. However, they probably have no effect on the long-term rate of cognitive deterioration.

One recent study suggests that antioxidant drugs such selegiline and alpha-tocopherol (vitamin E) may slow functional deterioration in patients with moderately advanced AD. In a two-year double-blind study, when compared to a placebo, both drugs were found to delay the time to reach the primary outcome (death, institutionalization or severe dementia), by five to seven months. More research is needed on the use of these drugs to treat AD.

Other experimental approaches for pharmacological treatment of cognitive disturbance in AD include estrogen, nonsteroidal anti-inflammatory drugs (NSAIDs), and ginkgo biloba. Epidemiological studies have reported that both estrogen and NSAIDs may decrease the risk for AD, and research is underway to determine whether estrogen improves cognition in women with AD.

"What Treatments Are on the Horizon?: Current and Anticipated Strategies for Families Caring for Patients with AD," Linda Teri, PhD
In addition to memory problems, there are other concerns that may affect a person with AD and their caregiver, including depression, agitation, and paranoia. Although drugs have been used in the past to treat these problems, research at the UW has shown that behavioral management techniques are also effective in reducing these behavior problems.

Research indicates that problem behaviors always include a triggering event (often called the antecedent), the behavior itself, and the immediate consequence of the behavior.

Caregivers who participate in behavioral studies learn five steps to analysis and management of behavior problems:

One key to success in this program is good communication. Aspects of good communication include: allowing enough time; demonstrating visually; maintaining good non-verbal behavior; providing cues and suggestions; using clear language; and doing one task at a time. At the UW, research is currently examining specific caregiver and patient characteristics that lead to successful problem solving, so that behavioral interventions can be improved further.

"Is Alzheimer'S Disease Different in Different Peoples?: Research Findings in Cross-Cultural Research on AD," Jay Uomoto, PhD
Many people wonder why we study dementia across cultures. By investigating the rates of dementia occurrence across cultures, we may identify environmental, physical, or genetic differences that are involved in the development of AD. We may also discover that different treatments are more or less effective for different cultures. We also know that developing countries contain over half of the world's population of older adults, but there is little information on dementia in these countries. Recent cross-cultural research has demonstrated that:

There are cultural differences in responses of family members to the onset of AD, but caregiver burden appears to be similar across cultures. Population-specific environmental risk factors are still being researched. Such studies will further our understanding of the causes of AD, and may lead to the development of preventive strategies.

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