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Dementia with Lewy bodies: Impact of co-pathologies and implications for clinical trial design

Lookup NU author(s): Emeritus Professor Ian McKeith, Professor John-Paul TaylorORCiD


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© 2022 the Alzheimer's Association.Dementia with Lewy bodies (DLB) is clinically defined by the presence of visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheimer's disease, TAR DNA-binding protein 43 (TDP-43), and cerebrovascular pathologic cases. Due to their high prevalence and clinical impact on DLB individuals, clinical trials should account for these co-pathologies in their design and selection and the interpretation of biomarkers values and outcomes. Here we discuss the frequency of the different co-pathologies in DLB and their cross-sectional and longitudinal clinical impact. We then evaluate the utility and possible applications of disease-specific and disease-nonspecific biomarkers and how co-pathologies can impact these biomarkers. We propose a framework for integrating multi-modal biomarker fingerprints and step-wise selection and assessment of DLB individuals for clinical trials, monitoring target engagement, and interpreting outcomes in the setting of co-pathologies.

Publication metadata

Author(s): Toledo JB, Abdelnour C, Weil RS, Ferreira D, Rodriguez-Porcel F, Pilotto A, Wyman-Chick KA, Grothe MJ, Kane JPM, Taylor A, Rongve A, Scholz S, Leverenz JB, Boeve BF, Aarsland D, McKeith IG, Lewis S, Leroi I, Taylor JP

Publication type: Review

Publication status: Published

Journal: Alzheimer's and Dementia

Year: 2022

Pages: epub ahead of print

Online publication date: 14/10/2022

Acceptance date: 09/09/2022

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: John Wiley and Sons Inc


DOI: 10.1002/alz.12814

PubMed id: 36239924