Research to halt the harms caused by Alzheimer's disease has yielded promising insights and strategies to help people remain cognitively healthy. Now, a new infusion of money to a landmark study tracking older adults will allow researchers to bring about more effective treatments and ways to prevent the disease.
The National Institute of Aging, part of the National Institutes of Health, is awarding a grant expected to total $55.6 million to the Adult Changes in Thought study (ACT), led by Kaiser Permanente Washington, the University of Washington and the University of California, San Diego. The funds will be used to advance the understanding of Alzheimer's and diversify and broaden participation in the study.
The study personnel will grow to 41 investigators at 10 research institutions across the United States and Canada, including 22 investigators from nine departments in five schools at the University of Washington: Built Environments, Pharmacy, Nursing, E-Science Institute, and Medicine.
Alzheimer's, the most common form of dementia, is a progressive and highly variable disease in which symptoms gradually worsen over a number of years. According to the Alzheimer's Association, it affects an estimated 6 million Americans. On average, a new person is diagnosed with Alzheimer's every 65 seconds. Today, there is a worldwide effort to find better ways to treat patients experiencing the disease, delay its onset, and prevent it from developing altogether.
Dr. Eric Larson, the senior investigator at Kaiser Permanente Washington Health Research Institute, who founded the ACT study in Seattle in 1994, is co-principal investigator along with Dr. Paul Crane, professor of medicine at the UW School of Medicine, and Andrea LaCroix, professor of and chief of epidemiology at University of California San Diego.
"This grant launches us into the next realm of investigation," said Crane. He started working on the ACT study nearly 20 years ago as a fellow at the UW Department of Medicine, and worked with Larson as ACT's co-principal investigator for the past several years.
Since it began, the ACT study has enrolled more than 5,800 older adults who receive care as Kaiser Permanente Washington members. Researchers track participants to find out which ones remain healthy as they age, which ones develop dementia, and how the condition manifests itself. The new five-year grant will increase the current study group of 2,000 members to 3,000. The enrollment effort will include new strategies to recruit a more diverse population.
"We have become a dynamic 'living laboratory' of aging," said Larson. "Thanks to the generosity of the ACT volunteers, we can investigate years of detailed medical records for study participants - often dating back decades before the study began because of their membership in Kaiser Permanente Washington - and do state-of-the-art studies of the brains from those who consent to autopsy."
More than 900 study participants arranged for their brains to be donated to the study after they died. These donations have allowed ACT to establish a brain bank tied to a community health care system with comprehensive electronic health records of the donors' care at Kaiser Permanente Washington and its precursor, Group Health Cooperative. The grant will allow these and other data from ACT to be digitized and shared with researchers worldwide, further cementing the study's role as an important repository for data on older adults.
As part of the new funding, researchers will pursue three research projects:
- One will examine relationships between device-measured physical activity and sleep over the 24-hour day and brain aging and dementia. Susan McCurry from the UW School of Nursing leads this project together with Dori Rosenberg from Kaiser Permanente Washington.
- A second project will characterize subtypes of Alzheimer's dementia to see whether they have different brain imaging or neuropathology findings, and whether people with these different subtypes have different experiences with dementia. Dr. Crane leads this project together with Janelle Taylor from the University of Toronto.
- A third project will study the effects of commonly used drugs that the ACT Study has shown can influence dementia risk. The study will examine the drugs' effects on neuron cells grown from participant cells using state-of-the-art stem cell approaches. Dr. Shelly Gray from the UW School of Pharmacy leads this project with Dr. Jessica Young from the UW School of Medicine's Department of Pathology and Laboratory Medicine.
These and other ACT projects build on a legacy of ACT findings, published in dozens of studies, that have advanced the understanding of dementia. ACT researchers have identified and quantified numerous factors that affect brain aging, including early life exposures, education, hearing and vision loss, traumatic brain injuries, hypertension, alcohol consumption, obesity, smoking, depression and social isolation, physical inactivity, and blood sugar levels and diabetes. A few examples from findings have shown:
- Frequent exercisers had a 38% lower incidence of Alzheimer's disease and dementia than those exercising three or fewer times per week.
- Higher blood glucose levels are associated with an 18% increased risk of Alzheimer's disease and dementia in people without diabetes and a 40% increased risk in people with diabetes.
- 47% of cognitively normal brains had substantial neuritic plaque density, and 33% had microinfarcts, which runs counter to a widespread view that such markers are reliable indicators of Alzheimer's disease and dementia.
- The study has linked a number of medications to a higher risk for developing dementia.
"As both an epidemiologist and the daughter of a mom now suffering from Alzheimer's disease, I have a deep commitment to finding ways to improve brain aging," said. LaCroix, who was involved at the start of the study. "We are all indebted to the ACT community participants past, current, and future, who will be working with us on these discoveries over the next five years and beyond."
The grant is divided into six cores: 1) Clinical Core is led by Larson from Kaiser Permanente Washington. 2) Life Course Core is led Sarah Tom from Columbia University and La Croix from UC San Diego. 3) Neuropathology Core is led by Dr. Dirk Keene from Department of Pathology and Laboratory Medicine at the UW School of Medicine. 4) Neuroimaging Core is led by Dr. Christine Mac Donald from the Department of Neurosurgery at UW School of Medicine. 5) Data and Analysis Core is led by Jennifer Nelson and Rod Walker from Kaiser Permanente Washington. 6) Administration Core is led by KatieRose Richmire from Kaiser Permanente Washington.
The ACT team also includes faculty and staff from Boston University, Columbia University, Swedish Medical Center in Seattle, University of California Riverside, University of Pennsylvania, University of Toronto, and University of Wisconsin-Madison. ACT is funded by NIH grant number U19AG066567.
