Alzheimer's Imaging Consortium.

Area of Science:

• Neuropathology
• Neuroimaging
• Geriatric Medicine

Background:

• Limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) frequently co-occurs with Alzheimer's disease neuropathologic change (ADNC).
• Hippocampal sclerosis (HS), associated with LATE-NC, contributes to memory deficits independently of AD.
• While FDG-PET and MRI studies have identified temporo-limbic signatures and hippocampal atrophy in HS, the brain-wide atrophy pattern in LATE-NC-associated HS requires further characterization.

Purpose of the Study:

• To characterize the brain-wide MRI-based atrophy pattern associated with LATE-NC and HS.
• To investigate if this pattern differs from AD without HS.
• To explore the relationship between HS severity and regional brain volumes.

Main Methods:

• Studied 84 dementia patients with detailed neuropathologic assessment and ante-mortem 3T-MRI.
• Assessed ADNC, LATE-NC, and HS using binary and staging schemes.
• Analyzed MRI data using ROI-based analyses across 52 brain regions, comparing autopsy cases to 1032 healthy controls.

Main Results:

• Dementia cases with LATE-NC+HS and AD-noHS exhibited similar brain-wide atrophy, most pronounced in medial/anterior temporal and lateral temporo-parietal areas.
• LATE-NC+HS cases showed significantly greater atrophy in the hippocampus, amygdala, temporal pole, insula, and orbitofrontal cortex compared to AD-noHS.
• A strong correlation was found between HS severity staging and temporo-limbic atrophy patterns across all autopsy cases.

Conclusions:

• LATE-NC-associated HS is linked to an in-vivo MRI atrophy pattern extending beyond the hippocampus.
• This extended atrophy involves temporo-limbic cortical areas affected by TDP-43 pathology in LATE-NC.
• The identified MRI signature may improve the clinical detection of LATE-NC-associated HS.