Dementia with Lewy Bodies: Impact of Co-pathologies and Implications for Clinical Trial Design

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2022 Oct 14

PMID 36239924

Authors

Jon B Toledo

Carla Abdelnour

Rimona S Weil

Daniel Ferreira

Federico Rodriguez-Porcel

Andrea Pilotto

Kathryn A Wyman-Chick

Michel J Grothe

Joseph P M Kane

Angela Taylor

Arvid Rongve

Sonja Scholz

James B Leverenz

Bradley F Boeve

Dag Aarsland

Ian G McKeith

Simon Lewis

Iracema Leroi

John P Taylor

Affiliations

Soon will be listed here.

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.

Citing Articles

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