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

Jon Toledo*, Carla Abdelnour, Rimona Weil, Daniel Ferreira, Federico Rodriguez-Porcel, Andrea Pilotto, Kathryn Wyman-Chick, Michel Grothe, Joseph Kane, Angela Taylor, Arvid Rongve, Sonia Scholz, James B. Leverenz, Bradley F. Boeve, Dag Aarsland, Ian G McKeith, Simon J G Lewis, Iracema Leroi, John-Paul Taylor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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Abstract

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.
Original languageEnglish
JournalAlzheimer's & Dementia: The Journal of the Alzheimer's Association
Early online date14 Oct 2022
DOIs
Publication statusEarly online date - 14 Oct 2022

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