Evaluating the updated LATE-NC staging criteria using data from NACC

• Published in: Alzheimer's & dementia
• Main Authors: Woodworth, Davis C, Nguyen, Katelynn M, Sordo, Lorena, Scambray, Kiana A, Head, Elizabeth, Kawas, Claudia H, Corrada, María M, Nelson, Peter T, Sajjadi, S Ahmad
• Format: Journal Article
• Language: English
• Published: United States 01.10.2024
• Subjects: limbic predominant age‐related TAR DNA‐binding protein of 43 kDa encephalopathy neuropathologic change; amygdala; hippocampus; hippocampal sclerosis of aging; dementia; Alzheimer's disease; National Alzheimer's Coordinating Center; neuropathology
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.14262

Limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data. We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models. Of 1352 participants, 502 (37%) had LATE-NC (23% stage 1a, 6% stage 1b, 58% stage 2, 13% stage 3). LATE-NC stages were associated with cognition, hippocampal sclerosis of aging (HS-A), Alzheimer's disease NC (ADNC), Lewy bodies (LBs), and hippocampal atrophy. While stage 1b was associated with cognition and HS-A consistent with other stages, it was not associated with ADNC or LBs. All LATE-NC stages remained significantly associated with worse cognition when accounting for other NCs. The updated LATE-NC staging criteria capture variations in early TDP-43 pathology spread which are consequential for cognition and associations with other NCs. We applied the updated limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria to data from the National Alzheimer's Coordinating Center. LATE-NC stage 1b was identified in 22% of participants with stage 1. In contrast to other LATE-NC stages, stage 1b was not associated with Alzheimer's disease neuropathologic change (ADNC) or Lewy bodies. Stages 1a and 1b were significantly associated with dementia and memory impairment. Stages 1b+ were more strongly tied to dementia than all other neuropathologic changes except high likelihood ADNC.