Finding effective treatments, cure at Alzheimer's Disease Center
It was about eight years ago when Sacramento resident Betty Lewis came to a disturbing realization. "She said to me one day, 'I can't remember anything anymore,' " recalls her daughter, Karen Gallay.
It wasn't long before Lewis saw her doctor, who sent her to the UC Davis Alzheimer's Disease Center. The diagnosis wasn't good: Alzheimer's disease.
Since then, Lewis, who is 78, has declined slowly. She's never left alone for extended periods of time and needs frequent supervision. Gallay, her primary caregiver, says her mother's social skills have diminished and that she occasionally fails to recognize her family. "She doesn't recall her brother's name, and sometimes she thinks I'm her sister."
Managing day to day
Since there's no cure for Alzheimer's, researchers at the center haven't been able to reverse the course of Lewis' disease, which disrupts brain function, particularly memory, through the accumulation of insoluble plaques and tangled neurons. The medical staff at the center has nonetheless helped Lewis – notably by putting her on a drug that reduces abnormal brain excitement and makes it easier for those with Alzheimer's to think clearly and perform daily tasks.
"That has helped tremendously," Gallay says.
Through the center, Lewis was also able to participate in an ongoing clinical trial of Huperzine A, a natural cholinesterase inhibitor derived from a Chinese herb. The herb is the primary treatment in China for Alzheimer's.
"It gave her a little more ambition to go out and do things," her daughter says.
— Charles DeCarli, UC Davis Alzheimer's Disease Center Director
UC Davis' Alzheimer's Disease Center has been helping others like Lewis for more than two decades through clinical and basic research and through caregiver support.
The center was formed in 1985 with funding from the California Department of Health Services. It initially operated at two locations: one was in Sacramento, the other at Alta Bates Medical Center in Berkeley.
"It was just three offices and a small suite and a couple of people," recalls Bruce Reed, one of the center's longest-serving scientists. The Berkeley center later relocated to roomier quarters in Martinez where the Department of Veterans Affairs Northern California Health Care System had research space available.
A major turning point came in the early 1990s, when the two sites successfully competed for a grant from the National Institute on Aging. Today, the center boasts an annual budget of about $4 million – from the state and federal governments – and 50 to 60 scientists and support staff. It's presently involved in up to 30 research projects, collaborative studies and clinical trials.
One of the best known studies is the Sacramento Area Latino Study on Aging, or SALSA, an assessment of the prevalence and risk factors for dementia in 1,800 Latinos 60 years and older. The longitudinal cohort study, launched in Sacramento by then-UC Davis researcher Mary Haan, has been going on for about 10 years and has zeroed in on the impact high blood pressure, atherosclerosis and inflammation have in contributing to the dementia.
Haan, who is now a professor of epidemiology at the University of Michigan School of Public Health, and her team have found strong evidence linking Type 2 diabetes to an increased risk of Alzheimer's.
The UC Davis center also is participating in a collaboration with investigators at UCSF, UCLA and the University of Southern California. This study is looking at the contribution of cerebrovascular lesions to behavioral alterations in those with dementia.
Charles DeCarli, an expert in imaging of aging brains, joined the center in 2000 and took over as director three years ago. He is heading up another long-term dementia study of 650 patients from three ethnic groups: Caucasian, African-American and Hispanic. The study, still in its early stages, involves regular cognitive testing and brain screening. However, several preliminary findings include:
- Debunking the widely held theory that African Americans and Hispanics are more likely to get Alzheimer's disease than other groups. In fact, DeCarli says his team is finding that the two groups do not have greater susceptibility. Still, he is looking to see if "subtle genetic differences" between the racial groups play a role in either the onset or severity of the disease.
- Alzheimer's and other types of dementia are over-diagnosed in non-white ethnic groups.One of the best known studies is the Sacramento Area Latino Study on Aging, or SALSA, an assessment of the prevalence and risk factors for dementia in 1,800 Latinos 60 years and older."Lots of times what seems to be cognitive impairment is really just a lack of education and limited English-language skills," DeCarli says.
Long-time center researcher Dan Mungas has played a key role in correcting this. An expert in neuropsychological statistics, Mungas has developed a method that takes into account cultural and linguistic differences when assessing performance on cognition tests.
"When you consider that 12 to 15 percent of California's population is Latino and they are aging, then you can see why we need tools to accurately diagnose dementia in minority groups," DeCarli says of Mungas' work.
While research participants are all given the same tests to measure skills such as verbal and spatial memory, Mungas applies a statistical method to adjust scores based on educational levels.
- A stimulating environment early in life appears to have a protective effect against Alzheimer's.
This has bubbled to the surface since the ethnicity study has enabled researchers to compare people of varying educational levels. They've found that those with little education are hit harder by Alzheimer's.
Exactly why is unclear, but DeCarli suspects it has something to do with the brain's wiring that is set in childhood.
"We don't know if it's greater synaptic density or more effective transmissions within the brain, but it's clear that an enriching environment early in life makes the brain stronger." This doesn't mean that exposing children to Mozart will prevent them from getting Alzheimer's later on. Rather, DeCarli says early stimulation should enable them to better tolerate the disease if they do get it.
- Researchers who go out into the community get a clearer picture of the actual rates of Alzheimer's and cerebrovascular disease, which also causes dementia.
"If you sit back in the clinic and wait for people to come to you, you're going to unwittingly select for people who just have Alzheimer's. People with cerebrovascular disease are sicker," says UC Davis researcher Reed.
Memory loss for them may not be their number one problem, so they aren't as likely to come into an Alzheimer's center.
Toward that end, the center established two minority outreach clinics, one in Stockton, the other in Oakland in the 1990s with a portion of its federal funding. Both are still going strong.
This kind of outreach, combined with studies like DeCarli's and SALSA, "has helped to raise the visibility of dementia and Alzheimer's" among minority groups, Michigan researcher Haan says.
As for Karen Gallay's mother, who is participating in DeCarli's study, the center has become a social hangout of sorts.
"She loves going there and interacting with the staff," Gallay says. Gallay herself has also come to rely on the center.
"When Mom's really off, I can call one of the nurses for advice. Sometimes, I just need someone who'll listen."