Alzheimer's Imaging Consortium

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.