Core F: University of Kentucky Alzheimer's Disease Core Center

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Project Summary/Abstract: Biomarker Core The theme of our UK-ADRC is Transitions from normal to late-life multi-etiology dementia, and the role of the Biomarker Core is to provide data and support efforts to develop biomarker profiles for the spectrum of underlying pathologies that can contribute to an individual’s cognitive decline. The Biomarker core will provide critical characterization of our cohort during their cognitively normal state, and through their cognitive transitions. The utility of biomarkers is expanding rapidly, as the dementia field identifies potentially disease- modifying therapies. Rather than focusing on a single biomarker modality (i.e. MRI, PET, plasma etc.), we have adopted a multimodal approach to biomarker characterization. Because our center is particularly interested in multi-etiology dementia, the most common dementia in the normal aging population, we believe a multimodal approach to biomarkers will yield novel insights into the progression of such complex dementias. We propose to measure blood- and CSF-based biomarkers for AD, cerebral small vessel disease (cSVD), large-vessel ischemic disease, and inflammation. In addition, we will perform state-of-the-art MRI imaging incorporating biomarkers of AD, cSVD and neuroinflammation. We will also explore the utility of wearable devices to collect digital biomarkers tracking sleep and physical activity, especially given that Lewy body pathology can lead to early sleep disturbances. Finally, digital gait assessment will provide physical biomarkers of gait, which has been shown to decline early in individuals with cSVD and Lewy body dementia. Importantly, the Biomarker Core has been established for several years and is fully integrated within the UK-ADRC, working closely with the other cores to maximize the utility of the biomarker data collected to date. We will continue to support internal and external research projects on biomarkers, and will also contribute significantly to national and international consortium efforts to develop clinic-ready biomarkers for AD, VCID, and other underlying causes of dementia. Our specific aims are: Aim 1: Collect bi-annual blood-based biomarkers of AD, cSVD, large vessel disease, and inflammation. Aim 2: Collect baseline MRI scans and accompanying CSF ATN biomarkers on all cognitively normal participants in the longitudinal cohort. Aim 3: Fully characterize biomarkers on all participants at their clinical transition from cognitively normal / preMCI to MCI, and from MCI to dementia. Aim 4: Determine the utility of digital biomarkers including activity, sleep, and gait, in predicting cognitive decline and / or brain pathology. Aim 5: Contribute to national efforts to establish, harmonize, and standardize biomarkers including NACC, ADNI, and NCRAD. Aim 6: Integrate with the other cores of the UK-ADRC.