Free-water in hippocampus is more sensitive than volume

Ofori E1DeKosky ST2Febo M3Colon-Perez L4Chakrabarty P5Duara R6Adjouadi M7Golde TE5Vaillancourt DE8Alzheimer’s Disease Neuroimaging Initiative.

Validating sensitive markers of hippocampal degeneration is fundamental for understanding neurodegenerative conditions such as Alzheimer’s disease. In this paper, we test the hypothesis that free-water in the hippocampus will be more sensitive to early stages of cognitive decline than hippocampal volume, and that free-water in hippocampus will increase across distinct clinical stages of Alzheimer’s disease. We examined two separate cohorts (N = 126; N = 112) of cognitively normal controls, early and late mild cognitive impairment (MCI), and Alzheimer’s disease. Demographic, clinical, diffusion-weighted and T1-weighted imaging, and positron emission tomography (PET) imaging were assessed. Results indicated elevated hippocampal free-water in early MCI individuals compared to controls across both cohorts. In contrast, there was no difference in volume of these regions between controls and early MCI. ADNI free-water values in the hippocampus was associated with low CSF AB1-42 levels and high global amyloid PET values. Free-water imaging of the hippocampus can serve as an early stage marker for AD and provides a complementary measure of AD neurodegeneration using non-invasive imaging.