Intra-Hippocampal Connectivity Differences in Cognitively Normal Subjects with/without Genetic Risk for Alzheimer’s Disease

Motivation: Microstructural changes within the hippocampus, which may occur well before cognitive decline in Alzheimer’s disease (AD), could serve as an early diagnosis biomarker in pre-symptomatic subjects.<hr align="left" size="1" width="33%">Goal(s): We assessed differences in intra-hippocampal connectivity between cognitively normal carriers and non-carriers of the APOE4 allele, a genetic risk factor for AD. Approach: We segmented the hippocampus into 12 subfields per hemisphere and performed fiber tractography on multi-shell diffusion tensor imaging data to determine the number of streamlines connecting each subfield pair. Results: 22 subfield pairs had a significantly lower connectivity in the APOE4 carrier group compared to the APOE4 non-carrier group. Impact: Our analysis shows differences in intra-hippocampal connectivity between cognitively normal subjects with and without a genetic risk factor for Alzheimer’s disease, which could potentially serve as a more definitive biomarker for its early diagnosis and treatment in pre-symptomatic subjects.