Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease

Kathryn Gauthreaux, Charles Mock, Merilee A. Teylan, Jessica E. Culhane, Yen Chi Chen, Kwun C.G. Chan, Yuriko Katsumata, Peter T. Nelson, Walter A. Kukull

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy is the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). LATE-NC is a common copathology with Alzheimer disease neuropathologic change (ADNC). Data from the National Alzheimer's Coordinating Center were analyzed to compare clinical features and copathologies of autopsy-confirmed ADNC with versus without comorbid LATE-NC. A total of 735 participants with ADNC alone and 365 with ADNC with LATE-NC were included. Consistent with prior work, brains with LATE-NC had more severe ADNC, more hippocampal sclerosis, and more brain arteriolosclerosis copathologies. Behavioral symptoms and cognitive performance on neuropsychological tests were compared, stratified by ADNC severity (low/intermediate vs high). Participants with ADNC and LATE-NC were older, had higher ADNC burden, and had worse cognitive performance than participants with ADNC alone. In the low/intermediate ADNC strata, participants with comorbid LATE-NC had higher prevalence of behavioral symptoms (apathy, disinhibition, agitation, personality change). They also had worsened performance in episodic memory and language/semantic memory. Differences narrowed in the high ADNC strata, with worsened performance in only episodic memory in the comorbid LATE-NC group. The co-occurrence of LATE-NC with ADNC is associated with a different pattern of behavioral and cognitive performance than ADNC alone, particularly in people with low/intermediate ADNC burden.

Original languageEnglish
Pages (from-to)975-987
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume81
Issue number12
DOIs
StatePublished - Dec 1 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s).

Keywords

  • Alzheimer disease
  • Depression
  • Lewy body
  • Limbic predominant age-related TDP-43 encephalopathy
  • Neuropsychiatric
  • TDP-43

ASJC Scopus subject areas

  • General Medicine

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