Clinical Core

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

Clinical Core-Project Summary The University of Washington (UW) Alzheimer Disease Research Center (ADRC) Clinical Core is a central resource supporting ADRD research at the University of Washington. Advances in human genetics, pathology and imaging technologies have revealed the biological diversity of ADRD, but how these diseases are rightly divided for purposes of clinical research remains to be determined. The Clinical Core aims to capture aspects of the clinical heterogeneity of ADRD, particularly cognitive and anatomic variability, and variability in resilience (cognitive reserve) to AD, in a longitudinal observational cohort. We also continue to study genetic factors in AD, and multimorbidity. The deep phenotyping of this cohort will facilitate interpretation of our biological studies and investigation of the relationship of phenotype to underlying mechanisms. The mechanisms that underlie resistance and resilience to AD also offer avenues to potential AD therapeutic targets. Resilience is affected by medical comorbidities, social determinants of health, and socioeconomic factors, all of which tend to be correlated. By defining resilience as a higher level of cognitive ability than would be expected for a given burden of disease, we can operationalize resilience as the residual of the regression of cognitive measures on measures of disease burden, and study the risk factors from this biological perspective. We will recruit participants to the longitudinal cohort at the MCI stage, where this approach can help stratify high- and low-resilience participants. We will include participants presenting with MCI who are engaged in amyloid-clearing treatment. Participants with MCI are expected to evolve differing cognitive trajectories, and to be cognitively phenotyped consistently and stably at the point of conversion to dementia. The discoveries of this research must be relevant to all persons with memory loss, and we plan broad recruitment across race, ethnicity, and SES status to make our observational studies broadly representative. An important theme in our Center is bringing American Indians and Alaska Natives (AI/ANs), specifically, into mainstream ADRD research, building on our successful outreach efforts over the last 10 years. We will accomplish our recruitment aims in collaboration with the ORE cores which recruit individuals from the Memory Brain Wellness Center, the LatinX community and the Urban and rural living AI/AN communities. Our aims are to characterize a diverse longitudinal cohort, innovate and measure ADRD biomarkers, represent a diversity of factors which influence resilience, and to contribute to long term biological evaluation of those who are undergoing anti-amyloid or tau therapies.