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Neuroimage Clin. 2019;24:101985. doi: 10.1016/j.nicl.2019.101985. Epub 2019 Aug 22.

Free-water imaging of the hippocampus is a sensitive marker of Alzheimer's disease.

Author information

1
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville FL 32611, United States of America; College of Health Solutions, Arizona State University, Phoenix, AZ, United States of America. Electronic address: edward.ofori@asu.edu.
2
Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville FL 32611, United States of America.
3
Department of Psychiatry, University of Florida, Gainesville FL 32611, United States of America; Department of Neuroscience, University of Florida, Gainesville FL 32611, United States of America.
4
Department of Psychiatry, University of Florida, Gainesville FL 32611, United States of America.
5
Department of Neuroscience, University of Florida, Gainesville FL 32611, United States of America; Center for Translational Research in Neurodegenerative Diseases, University of Florida, Gainesville FL 32611, United States of America.
6
Wein Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33140, United States of America.
7
Center for Advanced Technology and Education, Florida International University, Miami, FL 33174, United States of America.
8
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville FL 32611, United States of America; Department of Neurology, University of Florida, Gainesville FL-32611, United States of America; Department of Biomedical Engineering, University of Florida, Gainesville FL-32611, United States of America.

Abstract

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.

KEYWORDS:

Free-water imaging; Hippocampus; Mild cognitive impairment; Neurodegeneration

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