The Group Health-University of Washington Adult Changes in Thought Study: A Living, Learning Laboratory for Aging and Multiple Chronic Conditions Research

Background/Aims: Delivery system-based research can meet today’s need for practical clinical evidence and provide opportunities for discovery in everyday populations, particularly for an increasing number of people with multiple chronic conditions. The evolution of the Adult Changes in Thought (ACT) study, a long-standing partnership between Group Health and University of Washington, demonstrates the value and lessons learned from a living laboratory on aging. Methods: We responded to a 1986 National Institute of Aging request for Alzheimer’s disease patient registries to identify people with incident Alzheimer’s disease (AD) at Group Health. Partnering with University of Washington allowed us to evaluate candidate genetic markers and develop a biobank. In 1994, we established the ACT study, a cohort of randomly selected people over age 65 without dementia. We initially recruited 2,581 participants, followed by an expansion cohort of 811, and a continuous replacement sampling strategy to replace participants who die, become demented or are lost to follow-up. We maintain a constant cohort of approximately 2,000 living persons who are followed every two years. Results: ACT has enrolled over 5,000 subjects, including over 1,000 cases of incident dementia (over 70% AD) and almost 600 autopsy cases, of which about half have extensive frozen tissues with a rapid autopsy protocol. Our biobank includes extensive genome-wide single nucleotide polymorphism, exome sequence and gene expression data. Our population-based neuropathology biobank is unique worldwide. Our collaboration started a learning laboratory for pragmatic trials, and contributed to the development of the Seattle Protocols for dementia care, descriptive studies of health services utilization, and widely accepted risk factor and outcome data for persons with AD. ACT has served as the parent grant for numerous studies involving genetics, neuroimaging, pharmacoepidemiology, neuropathology, traumatic brain injury, treatment trials, methods development and career development. Discussion: Studies of important age-related conditions will provide valid research results if based on a representative population. The ACT study created a platform for a population-based living laboratory on aging across a wide range of disciplines and scientific inquiry. Effective partnerships, including widespread data and specimen sharing, are foundational and critical for optimal success