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Summary
This summary is machine-generated.

Lower hippocampal volume identifies Limbic-predominant age-related TDP-43 encephalopathy (LATE) in Alzheimer's disease (AD) patients. This finding aids in diagnosing mixed AD/LATE cases and understanding disease progression.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Radiology

Background:

  • Diagnosing mixed Alzheimer's disease (AD) and Limbic-predominant age-related TDP-43 encephalopathy (LATE) is challenging due to overlapping symptoms and lack of in-vivo biomarkers.
  • Autopsy studies indicate greater hippocampal atrophy in AD patients with co-occurring LATE.
  • Identifying patients with both AD and LATE is crucial for accurate diagnosis and treatment.

Purpose of the Study:

  • To identify patients along the AD continuum who are enriched for LATE.
  • To utilize the lower quartile of hippocampal volume (HV) as a potential biomarker for LATE.
  • To explore distinct atrophy patterns and cognitive profiles in mixed AD/LATE cases.

Main Methods:

  • 164 cognitively impaired participants from ADNI underwent T1-MRI and amyloid/tau-PET scans.
  • Participants were grouped by HV quartiles and amyloid status into AD-only, LATE-only, and AD+LATE groups.
  • Surface-based regional thickness analysis examined atrophy patterns in the medial temporal lobe (MTL) and cognitive differences across four domains.

Main Results:

  • The AD+LATE group exhibited imaging features of LATE, lower cognitive scores, and higher tau-PET uptake compared to AD-only.
  • AD+LATE showed more severe anterior hippocampal and amygdala atrophy than AD-only, with similar patterns to LATE-only.
  • Longitudinally, AD+LATE demonstrated faster cognitive decline across all domains, suggesting a more aggressive disease course.

Conclusions:

  • A lower quartile of HV can identify patients on the AD continuum with LATE-like patterns, indicating underlying LATE pathology.
  • This HV percentile-based metric may aid in identifying mixed AD/LATE cases for clinical trials.
  • Findings support the relevance of HV as a biomarker for LATE in the context of AD research.