Left-Predominant Hippocampal Atrophy Associated With LATE-NC

Lama Rayyis¹, Hyunwoo Lee¹, Waad Alshammari¹, Julia Xie², Ian R. Mackenzie³

Ging-Yuek Robin Hsiung¹

1 Division of Neurology, The University of British Columbia, Vancouver, BC, Canada

2 The University of British Columbia, Vancouver, BC, Canada

3 Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

 

Background:

Limbic-predominant age-related TDP-43 encephalopathy (LATE) causes an amnestic syndrome that closely mimics Alzheimer’s disease and commonly co-occurs with it. No validated in vivo biomarkers exist for TDP-43 pathology yet, and diagnosis is confirmed postmortem. MRI-based surrogate markers may help identify limbic TDP-43 involvement during life. Prior autopsy and MRI studies suggest that a higher middle–inferior temporal gyrus (MITG)–to–hippocampus volume ratio may distinguish TDP-43 pathology from AD. We evaluated MRI volumetric measures in our autopsy-confirmed cohort with mixed dementias and LATE neuropathologic change (LATE-NC).

 

Methods:

We included 27 participants with autopsy-confirmed neuropathology and antemortem MRI from the University of British Columbia. MRI scans were acquired from clinical scanners between 2004 and 2022. The cohort encompassed Alzheimer's disease and/or Lewy body disease, with and without LATE-NC. Twelve individuals with LATE-NC (LATE+) were age- and sex-matched to 15 individuals without LATE-NC (LATE-). We quantified MRI-based hippocampal volumes (left, right, and mean) and MITG volumes using Statistical Parametric Mapping (SPM12), and calculated MITG-to-hippocampus volume ratios (Table 1). Three clinicians visually rated medial temporal atrophy (MTA) bilaterally and we analyzed mean left, right, and average MTA scores. We used a general linear model to compare volumetric and visual measures between groups, and examined relationships between visual MTA ratings and volumetric MRI measures using Spearman correlations (Table 2). 

Results:
Participants were predominantly right-handed (>80%) and 41% female, with mean age of onset 67.6 ± 7.3 years and mean age of death 77.0 ± 6.6 years. Visual MTA scores did not differ significantly between LATE+ and LATE- participants. Volumetric analysis demonstrated significantly reduced left hippocampal volume in LATE+ participants compared with LATE- participants (p = 0.04), while right and mean hippocampal volumes were not significantly different. MITG volumes and MITG-to- hippocampus volume ratios showed no significant group differences. Visual MTA scores correlated inversely with MITG volume (ρ = −0.42, p = 0.03) but not significantly with hippocampal volume (ρ = −0.24, p = 0.24). 

Conclusion:

LATE-NC was associated with significant left-predominant hippocampal atrophy detectable by volumetric MRI but not consistently by visual MTA ratings. Future longitudinal studies are needed to compare visual and SPM-based measures, characterize progression of asymmetry, and relate imaging findings to LATE stages to validate asymmetric hippocampal atrophy as a sensitive in vivo marker for LATE-NC.