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Summary
This summary is machine-generated.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease (AD) uniquely impact medial temporal lobe volume and cognitive decline. Identifying LATE-NC in life is crucial for understanding its role in dementia.

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Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Cognitive Aging

Background:

  • Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is prevalent in dementia, often co-occurring with Alzheimer's disease (AD).
  • Lack of in-vivo biomarkers for LATE-NC hinders clinical identification.
  • This study investigates the association of pathologically confirmed LATE-NC, with or without AD, with medial temporal lobe (MTL) volume and cognitive trajectories.

Purpose of the Study:

  • To evaluate the relationship between pathologically confirmed LATE-NC and AD.
  • To assess the impact of LATE-NC and AD on medial temporal lobe (MTL) subregional volumes.
  • To determine the effect of LATE-NC and AD on longitudinal cognitive decline.

Main Methods:

  • Analysis of 846 participants (age 70+) from the AD Sequencing Project Phenotype Harmonization Consortium.
  • Categorization based on post-mortem neuropathology for AD and LATE-NC.
  • Assessment of longitudinal cognitive domain scores (memory, executive function, language) and 3T brain MRI segmentation (MUSE).
  • Statistical analyses included ANOVA, chi-square, linear regression, and linear mixed effects models.

Main Results:

  • Both AD and LATE-NC were uniquely associated with MTL subregional volumes, except for the superior temporal gyrus.
  • The hippocampus was associated with LATE-NC but not AD pathology.
  • Participants with LATE-NC showed a faster rate of memory decline compared to those without LATE-NC, while AD pathology was linked to faster decline in executive function and language.

Conclusions:

  • AD and LATE-NC exhibit distinct associations with MTL volume and cognitive decline.
  • Understanding the clinical correlates of LATE-NC is vital for in-life diagnosis.
  • This research supports future studies on LATE-NC pathogenesis and clinical management.