Brain agingHumans

Lewy body disease tracks with cognitive decline and psychosis

Lewy body disease prevalence rose from 0.7% in individuals younger than 50 to 20.0% in those aged 90 and older across 2,480 autopsied human brains.

Movement Disorders4 Oct 2026, 08:49 BST

Researchers analyzed 2,480 autopsied brains from participants aged 73.25 years on average in the Biobank for Aging Studies in São Paulo, Brazil. They evaluated Braak Parkinson's disease stages alongside copathologies and conducted structured postmortem informant interviews covering cognition, neuropsychiatric symptoms, and motor signs. Overall, Lewy body disease was identified in 10.4% of donors. Advanced stages correlated with greater Alzheimer's disease-related pathology, TDP-43 pathology, and cerebral amyloid angiopathy. Only 26.1% of individuals with advanced pathology had a family-reported premortem Parkinson's diagnosis. In adjusted models, advanced stages remained associated with worse cognition, hallucinations, and delusions, while total parkinsonism score was not independently associated. Early pathology stages were already associated with nocturnal disturbances.

Why it matters

The findings show that Lewy body pathology escalates with age and frequently co-occurs with other age-related neurodegenerative proteinopathies. They indicate that late-stage synuclein pathology in the general population manifests primarily through cognitive and neuropsychiatric decline rather than caregiver-reported motor parkinsonism.

Caveats

The study relied on postmortem informant interviews rather than direct longitudinal clinical examinations to assess symptoms and premortem diagnoses. Informant-based assessments may underestimate or misclassify subtle parkinsonian or cognitive features.