Background and Objectives:Limbic predominant age related TDP-43 (LATE) impacts similar neuroanatomical networks as Alzheimer’s disease (AD) and is often comorbid with AD, though frequently missed in clinical diagnosis. The primary aim of this study was to elucidate the clinical and cognitive differences at baseline between patients with autopsy confirmed LATE, compared to patients with AD and comorbid LATE+AD.Methods:Clinical and neuropathological datasets were requested from the National Alzheimer’s Coordination Center (NACC). Baseline data from individuals 75+ years at time of death without neuropathological indication of frontotemporal lobar degeneration were included in analyses. Pathologically defined groups reflecting LATE, AD, and comorbid LATE+AD were identified. Group differences in clinical characteristics and cognition were explored through analysis of variance and chi-square using measures from the Uniform Data Set measures.Results:Pathology groups included 31 individuals with LATE (Mage: 80.6±5.4), 393 with AD (Mage: 77.8±6.4), and 262 with LATE+AD (Mage: 77.8±6.6) without significant differences in sex, education, or race. Compared to participants with AD and LATE+AD pathology, participants with LATE pathology lived significantly longer (Mvisits: LATE=7.3±3.7; AD=5.8±3.0; LATE+AD=5.8±3.0; F(2,683)=3.7, p<.05), reported later onset of cognitive decline (Monset: LATE=78.8±5.7; AD=72.5±7.0; LATE+AD=72.9±7.0; F(2,516)=6.2, p<.01), and were more likely to be diagnosed as cognitively normal at baseline (LATE=41.9%; AD=25.4%; LATE+AD=12%; χ2=38.7, p<.001). Individuals with LATE (45.2%) also reported fewer memory complaints than those with AD (74.4%) or LATE+AD (66.4%; χ2=13.3, p=.001) and were less likely to be classified as Impaired on the Mini Mental State Exam (LATE=6.5%; AD=24.2%; LATE+AD=40.1%; χ2=29.20, p<.001). Across all neuropsychological measures, participants with LATE+AD pathology performed significantly worse than the AD and LATE groups.Conclusions:Those with LATE pathology were older when cognitive symptoms began and lived longer than participants with AD or LATE+AD pathology. Participants with LATE pathology were also more likely to be classified as “cognitively normal” based on objective screening and self-report measures, and they had higher scores on neuropsychological testing. Consistent with prior literature, comorbid pathologies led to more significant cognitive and functional impairment. Early disease characteristics based on clinical presentation alone were insufficient for differentiating LATE from AD, reiterating the need for a validated biomarker.
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