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Association of white matter hyperintensities, white matter microstructural changes, hippocampal and amygdala volumes with neuropathology in a community cohort using 7T postmortem in situ MRI

Liou, J.-J.; Martin, M.; Rodriguez, R.; Grinberg, L.; Santini, T.; Ibrahim, T.; Otaduy, M.

2026-07-06 pathology
10.64898/2026.06.30.26356455 medRxiv
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INTRODUCTION: We integrate visual and quantitative metrics in white matter and medial temporal lobe to examine relationships with neuropathology in a community cohort. METHODS: Postmortem in situ MRI (T1, T2, DWI) was performed in 25 human brains, followed by visual ratings (Fazekas, MTA, ERICA, Koedam). Neuropathology included ADNC, LATE-NC, hippocampal sclerosis, PART, ARTAG, Lewy pathology, and CAA. RESULTS: Increased Fazekas score was linked to aging, lower education, hypertension, higher basilar artery wall thickness, and greater Braak NFT stage. WMH volume also correlated with lacunes, Thal phase, and CERAD score that was not observed using Fazekas. Hippocampal volumes were lower in elderly, less educated people and were associated with higher atrophy scores and higher Braak NFT stage. Higher amygdala volume was only associated with higher CERAD score. DISCUSSION: Quantitative MRI may detect neuropathologic associations more sensitively than visual ratings. Tau pathology is a key predictor of WMH burden and hippocampal atrophy.

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