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

• DOI: 10.1002/alz.14191
• Publication Date: 2024-12-23T07:50:40Z
• Authors: Francisco C. Almeida; Alexandra Santos; Tiago Jesus; Ana Coelho; Miguel Quintas‐Neves; Kathryn Gauthreaux; Charles N. Mock; Walter A. Kukull; John F. Crary; Tiago Gil Oliveira
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Research Article

AbstractINTRODUCTIONAlzheimer'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.METHODSWe 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.RESULTSLB 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.DISCUSSIONThese results suggest that LB co‐pathology is associated with divergent patterns of cognitive impairment, brain atrophy, and regional pathological distribution in PART and AD.Highlights 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.