The utility of a composite endpoint for tracking disease progression in Lewy body dementia.

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.