Lewy body co-pathology in Alzheimer's disease and primary age-related tauopathy contributes to differential neuropathological, cognitive, and brain atrophy patterns

• Published in: Alzheimer's & dementia 2024-12
• Main Authors: Almeida, Francisco C, Santos, Alexandra, Jesus, Tiago, Coelho, Ana, Quintas-Neves, Miguel, Gauthreaux, Kathryn, Mock, Charles N, Kukull, Walter A, Crary, John F, Oliveira, Tiago Gil
• Format: Article
• Language: English
• ISSN: 1552-5279; 1552-5279
• DOI: 10.1002/alz.14191

Alzheimer's disease (AD) co-pathology with Lewy bodies (LB) is frequent and influences clinical manifestations and outcomes. Its significance in primary age-related tauopathy (PART) is unknown. We investigated the influence of LB on cognition and brain atrophy in AD and PART. We performed a retrospective cohort study in a large sample of autopsied participants with AD neuropathological change (ADNC) with and without LB and PART with and without LB, with corresponding ante mortem magnetic resonance imaging (MRI) data from the National Alzheimer's Coordinating Center dataset. LB co-pathology worsened cognitive impairment in both PART and ADNC. On longitudinal follow-up, LB impacted cognitive decline in multiple domains. Additionally, LB influenced brain atrophy on MRI across groups and LB regional staging was different in PART and ADNC, accompanying tauopathy progression. These results suggest that LB co-pathology is associated with divergent patterns of cognitive impairment, brain atrophy, and regional pathological distribution in PART and AD. Lewy body (LB) co-pathology is frequent in Alzheimer's disease (AD) with important clinical implications. LB co-pathology is also present in primary age-related tauopathy (PART), but its significance is still understudied. In PART and AD, LB leads to higher cognitive impairment and brain regional atrophy. In PART and AD, LB tends to accompany neurofibrillary tangle progression, suggesting amyloid pathology might be a trigger for regional pathology progression.