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

Abstract

INTRODUCTIONLimbic‐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.METHODSWe 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.RESULTSOf 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.DISCUSSIONThe updated LATE‐NC staging criteria capture variations in early TDP‐43 pathology spread which are consequential for cognition and associations with other NCs.Highlights 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.