Study of aging in Group Health patients renewed with $12 million grant

Collaboration with University of Washington aims to prevent dementia, including Alzheimer's

Seattle—Every two years, 2,000 senior Group Health patients check in with the Adult Changes in Thought (ACT) study. The joint project between Group Health Research Institute and the University of Washington (UW) focuses on finding ways to delay or prevent dementia, including Alzheimer's disease, and declines in memory and thinking. It aims to deepen understanding of how the body—especially the  brain—ages.

The National Institute on Aging recently awarded the ACT study a grant of nearly $12 million to continue its work for the next five  ears. In continuous operation for 23 years, it is the longest-running study of  its kind.

"Thanks to our dedicated patients—and our team of  leading-edge scientists and staff at the UW and Group Health—the ACT study is a  'living laboratory' of aging," said study leader Eric B.  Larson, MD, MPH, executive director of Group Health Research Institute. "We've learned about what our research subjects value as they age. And we hope to help  them find the best solutions to age well—promoting their independence and  providing them with skills to cope with any problems that may occur."

At each biannual study visit, participants are observed as they walk and do many other physical and mental tasks. They are asked many questions, including whether they would allow an autopsy on their brains after they die. Thanks to willing participants, the study has gleaned its most recent discoveries, which center on how vascular (blood vessel) disease contributes to  late-life dementia, including Alzheimer's disease:

• Microscopic injuries to blood vessels in the brain, called cerebral "microinfarcts," which cause "small-vessel disease of the brain," can lead to many brain problems in late life.
• These microinfarcts may be responsible for more cases of dementia than previously recognized, often combined with Alzheimer's.
• Controlling high blood pressure may lower the risk of dementia by minimizing microinfarcts.

In the next five years, the ACT team will largely focus on deeper exploration of these most recent findings. They will test whether diabetes, kidney disease, and atrial fibrillation (the most common abnormal heart rhythm) contribute to brain decline through microinfarcts or changes in  larger blood vessels—and whether physical activity counters them. Ongoing trials also include interventions to improve sleep as well as thinking and physical well-being.

Like the celebrated Framingham Heart Study, ACT is a  longitudinal cohort study of people leading their lives in a community. That means it follows a large group of people at regular intervals over a long time  to see what happens to them. As with Framingham, insights from the study group have helped other people to stay healthier. ACT the only ‘population-based' study involving autopsy and study of diseases of nervous system tissue (neuropathology).

The ACT study has learned many lessons to date, published in nearly 250 scientific articles. The study is known best for findings about the  benefits of physical activity:

• Regular exercise is linked to reduced risk of dementia, Alzheimer's disease, and declines in how well people think.
• The first signs of dementia—including Alzheimer's disease—may be physical, not mental.
• For  example, when older people cannot walk except very slowly, this predicts that they are likely to become "frail" (weak and prone to diseases) and develop dementia.

Other study findings have led to changes in how people with dementia are cared for and helped ease the burdens these illnesses can cause.  Here are some examples:

• Certain drugs, especially sedatives, can cause confusion and falling.
• Statin drugs, used to treat high cholesterol, may be linked to fewer of the microscopic brain changes that are typical of Alzheimer's disease.
• Anti-oxidant supplements (vitamins A and C) and some common pain relievers (non-steroidal anti-inflammatory drugs, or NSAIDs) seem not to prevent brain decline.
• But a related study of Japanese-American seniors in King County linked regularly drinking fruit and vegetable juices—both rich sources of natural anti-oxidants—to reduced risk of Alzheimer's disease.
• Avoiding environmental toxins throughout life can help delay the brain's decline.
• Wearing shoes—not just socks, stockings, or slippery slippers—can help prevent falling, even at home.
• Wandering, agitation, and disturbed sleep complicate the lives of patients with Alzheimer's and their families.

The ACT study enrolls about 240 new people each year, keeping the study group size steady at about 2,000 people. People are invited  to participate after being randomly selected from a census of all Group Health members who are age 65, enrolled in central King County medical centers, and without dementia.

The participants have been patients at Group Health for an average of at least 30 years before joining the study. "That gives us a wealth of medical, drug, and lifestyle information to help answer our research questions," Dr. Larson said. "ACT is the world's only study that can link outcomes for dementia, frailty, and aging to data that captures each participant's whole health history, including medical, lab, and pharmacy  records."

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