In vivo microstructural mapping of the hippocampus in older adults with familial risk for Alzheimer’s disease

Motivation: Understanding prodromal Alzheimer’s disease is essential for treatment development. Hippocampal volume loss indicates significant atrophy and may occur too late to slow disease progression. Goal(s): We aimed to precisely map spatial variation in hippocampal microstructure in vivo using quantitative MRI in prodromal AD. Approach: We use multiparametric quantitative MRI to comprehensively map hippocampal microstructure in healthy older adults with first-degree family history of Alzheimer’s disease and correlate maps with demographic risk factors for Alzheimer's disease. Results: We identified two key contributors of microstructural variation (myelin content and free water). We revealed localized age-related demyelination and sex differences in hippocampal proton density. Impact: This research provides crucial insights into age-related hippocampal microstructural changes and their implications for Alzheimer's disease. It has the potential to advance early detection and intervention strategies, ultimately improving patient outcomes in Alzheimer's disease management.