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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.
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
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
PubMed id: 36239924