Project Summary It has been estimated that over 1.4 million people in the United States suffer from Lewy body dementia (LBD), including both dementia with Lewy bodies (DLB) or Parkinson's disease with dementia (PDD). Patients with LBD suffer from cognitive decline, sometimes linked to Alzheimer's disease (AD), and the motor and behavioral changes seen in Parkinson's disease (PD). Unfortunately, the diagnosis of LBD can be difficult, particularly in those DLB patients that present with cognitive impairment prior to motor or marked behavioral changes. While diagnostic biomarkers for LBD have been limited, recent developments have suggested that determining Lewy body pathology (LBP) and AD pathology change may be possible with biofluid biomarkers. Until recently, impediments to biomarker development in LBD have included small subject numbers, a lack of systematic patient characterization and a failure to perform longitudinal follow up with autopsy. Both AD and PD have benefited from a number of large “consortiums” that have advanced research by leveraging the strengths of several groups of research centers to combine efforts with standardized approaches to the study of the disease. One good example is the Alzheimer's Disease Centers (ADC) program, funded by the National Institute on Aging, where over 30 research centers across the United States have agreed to a standardized approach to the diagnosis and characterization of patients with AD. Other similar programs include the Alzheimer's Disease Cooperative Study (ADCS), Alzheimer's Disease Neuroimaging Initiative (ADNI), the National Institute of Neurological Disorders and Stroke (NINDS) Parkinson's Disease Biomarker Program (PDBP), and the Parkinson's Progression Marker Initiative (PPMI). Fortunately, the latter two PD programs have included more systematic clinical assessments and collection of biofluids and imaging data relevant to cognition in PD. Until funding of the Dementia with Lewy Body Consortium (DLBC), no similar US-based program had existed. The objective of this DLBC renewal proposal is to utilize and expand the DLBC cohort with additional subjects enrolled, continued longitudinal systematic assessments, collection of biofluids and imaging data, and ultimately autopsy. As a more hypothesis-driven renewal proposal, the DLBC will utilize the longitudinal data, imaging and biofluid collection from DLBC participants to focus on diagnosis, progression and clinical variability. Two new Co-Principal Investigators and a number of new co- investigators and collaborators will join the DLBC to enhance the additional focus on the new hypothesis-driven aims.