Lewy Body Disease Across Aging: Clinical and Neuropathological Correlates in a Population Brain Bank.
Abstract
Background
Lewy body disease (LBD) is defined by neuronal α-synuclein pathology, but how Braak-staged LBD relates to mixed neuropathology and clinical manifestations within a single population-based cohort remains incompletely characterized. This is especially relevant in cohorts enriched for younger individuals, which may better inform real-world biomarker interpretation and predictive value than cohorts dominated by the oldest-old.
Objective
The objective of this study was to determine how Braak-staged LBD relates to age, mixed neuropathology, and clinical manifestations within a single population-based cohort.
Methods
We studied 2480 autopsied participants from the Biobank for Aging Studies in São Paulo, Brazil (mean age 73.25 ± 14.15 years, 49.7% female, mean education 5.17 ± 4.23 years; 2004-2025). Structured postmortem informant interviews assessed cognition (CDR-SB), parkinsonian symptoms (Tanner questionnaire), neuropsychiatric symptoms (Neuropsychiatric Inventory), and family-reported premortem Parkinson's disease (PD) diagnosis. Brains were staged using Braak Parkinson's disease (Braak-PD) staging and evaluated for copathologies.
Results
Overall, 10.4% had LBD, increasing from 0.7% among those younger than 50 years to 20.0% among those aged ≥90 years. Advanced Braak-PD was associated with greater Alzheimer's disease-related neuropathology, TDP-43 pathology, and cerebral amyloid angiopathy. Approximately 26.1% of individuals with Braak-PD V-VI had a family-reported premortem PD diagnosis. In adjusted models, Braak-PD V-VI remained associated with worse cognition (β 3.03, 95% confidence interval [CI]: 1.93-4.14), hallucinations (odds ratio [OR] 3.87, 95% CI: 2.27-6.61), and delusions (OR 2.79, 95% CI: 1.61-4.82), whereas total parkinsonism score was not independently associated. Nocturnal disturbances were already associated with Braak-PD I-II (OR 2.25, 95% CI: 1.13-4.47).
Conclusions
In this population-based cohort, LBD becomes more frequent with age, occurs in a mixed-pathology context, and is more strongly expressed through cognition and psychosis-related symptoms than through caregiver-reported parkinsonian burden. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.