This multicenter, retrospective, autopsy-confirmed brain bank study evaluated clinicopathological correlation, diagnostic accuracy, genetic associations with pathology, and ancestry-related differences in 3,353 donors with parkinsonian disorders (or neurologically normal controls) from 11 academic brain banks in the UK, US, and Australia (enrolled 1985–2024).
Misdiagnosis rates ranged from ~10–20% across movement disorders. Dementia with parkinsonism (PDD/DLB) was more strongly linked to Lewy body pathology than PD without dementia (OR 1.96; 95% CI 1.30–3.04). GBA1 carriers had greater Lewy body burden than noncarriers (OR 1.94) and LRRK2 carriers (OR 7.44). AD copathology was present in 40% of Lewy body disease cases. Ancestry-related differences in pathology were significant: South Asian donors were more likely to have PSP pathology; Ashkenazi Jewish donors were more likely to have Lewy body disease (independent of GBA1/LRRK2 status).
- Brain bank cohorts have inherent selection bias (donors who consent to autopsy may not represent the broader parkinsonian population). - The study is cross-sectional and retrospective, limiting causal inference. - Full-text data were not available for detailed review; only abstract and results sections were accessible.
Clinicians should anticipate ~10–20% misdiagnosis rates in parkinsonian disorders and recognize that AD copathology is common in Lewy body disease (40% of cases). Genetic profiling (especially GBA1 status) and patient ancestry should inform diagnostic workup and future trial stratification.
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