Lewy Body Disease Across Aging: Clinical and Neuropathological Correlates in a Population Brain Bank
Vitor Ribeiro Paes, Felipe Luiz Pereira, Caroline Matos Silva, Filipe Oto Cunha de Moraes, Inês Liguori Padrão, Alberto Fernando Oliveira Justo, Roberta Diehl Rodriguez, Michel Satya Naslavsky, Renata Elaine Paraizo Leite, Carlos Augusto Gonçalves Pasqualucci, Mayana Zatz, Eduardo Ferriolli, Claudia Kimie Suemoto, Lea Tenenholz GrinbergAbstract
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.