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Lookup NU author(s): Professor John-Paul TaylorORCiD, Emeritus Professor Alan Thomas, Professor Ian McKeith
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.INTRODUCTION: Dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD), collectively termed Lewy body dementia (LBD), show heterogenous progression across cognitive, motor, and neuropsychiatric symptom domains, yet disease-specific endpoints are lacking. We evaluated whether a composite clinical endpoint using validated scales across different symptom domains could sensitively track disease progression and align with functional and caregiver outcomes. METHODS: One hundred sixteen participants (DLB = 72; PDD = 44) were assessed at baseline, 3, and 6 months in a cluster-randomized trial comparing usual care versus management informed by an evidence-based toolkit. The Lewy Body Symptom Severity (LBSS) index was constructed by summing rescaled Mini-Mental State Examination, Movement Disorder Society Unified Parkinson's Disease Rating Scale (Part III), Dementia Cognitive Fluctuations Scale, and Neuropsychiatric Inventory 4-item subscore (including hallucinations). Linear mixed-effects models tested change over time. Validity was examined against caregiver Clinical Rating of Change (CRC), Bristol Activities of Daily Living (ADL) Scale, and caregiver Zarit Burden Interview. RESULTS: Over 6 months, LBSS increased significantly (β = 0.0307; P = 0.0006). Simulation-based power analyses indicated greater statistical efficiency for LBSS than for any individual component. LBSS also detected a significant intervention effect (P = 0.0365) not observed with single-domain measures. LBSS correlated with caregiver burden (Zarit; ρ = 0.53, P < 0.001), functional dependence (Bristol ADL; ρ = 0.57, P < 0.001), and CRC (ρ = −0.33, P = 0.002), permitting derivation of a minimal clinically important difference. DISCUSSION: A simple composite spanning cognition, parkinsonism, cognitive fluctuations, and neuropsychiatric symptoms sensitively detected short-interval progression, with improved statistical efficiency over single-domain measures, and was aligned with functional/caregiver outcomes. These findings support composite endpoints for LBD trials and can inform the design of disease-specific scales.
Author(s): Matar E, White SR, Taylor J-P, Thomas A, McKeith I, Kane J, Lewis S, Surendranathan A, O'Brien J
Publication type: Article
Publication status: Published
Journal: Alzheimer's and Dementia: Translational Research and Clinical Interventions
Year: 2026
Volume: 12
Issue: 2
Print publication date: 01/04/2026
Online publication date: 20/05/2026
Acceptance date: 09/04/2026
Date deposited: 01/06/2026
ISSN (print): 2352-8737
ISSN (electronic): 2352-8737
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/trc2.70260
DOI: 10.1002/trc2.70260
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