Dementia with Lewy Bodies Consortium (U01)

It has been estimated that 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. Biomarkers for LBD are few and their value in diagnosis, prognosis, and for treatment response is limited. 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. Recently, a pathology component has been added to the PPMI project. No similar program exists for DLB. The objective of this proposal is to establish a consortium of centers for the study of DLB with a large number of subject enrolled, systematic assessments (compatible with AD and PD programs), collection of biofluids and imaging data, and ultimately autopsy. The DLB consortium (DLBC) would create the necessary foundation for biomarker development and have the secondary benefit of creating an ongoing subject sample available for additional translational and therapeutic studies. We have brought together nine centers with expertise in the Lewy body disorders and with strong connections to the Lewy body dementia research and general community to participate in the DLBC. This group of investigators has collaborated extensively together for many years and will provide the foundation for this much needed resource. PUBLIC HEALTH RELEVANCE: The Lewy body dementias are the second most common cause of dementia in the elderly. Research into this common form of dementia has been hindered by the need for large groups of patients to study in a consistent manner over time. The Dementia with Lewy Body Consortium will address this issue by bringing together a group of experts that will study a large number of patients from across the country over a two to five year period.

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. 

PUBLIC HEALTH RELEVANCE: The Lewy body dementias are the second most common cause of dementia in the elderly. Diagnosis can be difficult and determinants of clinical symptoms and progression are unclear. This renewal proposal will expand the current Dementia with Lewy Bodies Consortium (DLBC) participant numbers and utilize the deep phenotyping and biomarker characterization to improve upon diagnosis, prediction of progression, and clinical variability.

Goals of Project

• Resource Building: To establish the Dementia with Lewy Bodies Consortium (DLBC) with Thomas Jefferson University, Florida Atlantic University, Rush University, University of Pennsylvania, University of Pittsburgh, VA/Puget/University of Washington, University of California San Diego, University of North Carolina and headed by Cleveland Clinic.
• Resource Building: To establish a DLBC coordinating center to provide oversight of the DLB consortium activities, coordinate annual meetings, etc.
• Recruitment: To develop a large registry (216 subjects) of individuals with probable Dementia with Lewy Bodies (DLB) or high likelihood DLB subtype of mild cognitive impairment (MCI) by bringing together multiple clinical investigation sites with expertise in Lewy Body Dementia (LBD).
• Assessment: To systematically and longitudinally evaluate these Dementia with Lewy Bodies (DLB) subjects with cognitive, motor, and behavioral characterization and to enter this data into the PDBP database.
• Sample Collection: To systematically and longitudinally collect biofluids from DLB subjects and to enter biofluids samples into the PDBP biorepository.
• Assessment: To obtain autopsy for the pathologic characterization of brain and collection of tissues for additional investigations.
• Facilitate Collaboration: To promote collaboration across both the DLB consortium sites and with other investigators, including other consortiums outside the US, in order to accelerate biomarker and translational research and the development of therapeutic interventions of LBD.

Enrollment Goals

• 216 subjects with probable Dementia with Lewy Bodies (DLB) or high likelihood DLB subtype of mild cognitive impairment (MC)  (varying stages of disease.