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Clinical Manifestations.

Yara Alkhodair1,2, Imogene M Scott1, Abdulrahman Alzahrani1

  • 1Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) did not increase overall neuropsychiatric symptoms in individuals with Alzheimer's disease and/or Lewy body disease. Hallucinations were less frequent in the LATE-NC group.

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Area of Science:

  • Neuropathology
  • Neuropsychiatry
  • Geriatric Medicine

Background:

  • Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) often co-occurs with Alzheimer's disease (AD), Lewy body disease (LBD), and vascular pathology.
  • While neuropsychiatric symptoms in AD/LATE-NC are increasingly studied, their impact in mixed AD/LBD and LBD remains underexplored.

Purpose of the Study:

  • To investigate and compare neuropsychiatric symptom profiles in individuals with AD, LBD, and mixed AD/LBD, with and without LATE-NC.
  • To analyze the influence of LATE-NC on the severity and progression of neuropsychiatric symptoms in these patient groups.

Main Methods:

  • Retrospective cohort study of autopsy-confirmed cases from the UBCH-CARD database.
  • Matching of 42 LATE-NC positive (LATE+) cases with 38 LATE-NC negative (LATE-) cases based on age and neuropathology.
  • Assessment of neuropsychiatric symptoms using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and analysis of longitudinal data using linear mixed-effects models.

Main Results:

  • No significant differences in overall neuropsychiatric symptom severity or longitudinal burden were found between LATE+ and LATE- groups.
  • Apathy, hallucinations, and appetite changes were less severe in the LATE+ group.
  • Hallucinations remained significantly less frequent in the LATE+ group even after adjusting for coexisting pathologies.

Conclusions:

  • LATE-NC does not appear to exacerbate the overall neuropsychiatric symptom burden in individuals with AD and/or LBD.
  • The reduced frequency of hallucinations in the LATE+ group warrants further investigation, potentially related to Lewy body pathology.
  • Longitudinal modeling of symptom progression requires further analysis to fully understand LATE-NC's impact.