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2011 Grants - Kerchner
Hippocampal Striatal Anatomy in Mild Cognitive Impairment: A 7T MRI Study
Geoffrey A. Kerchner, M.D., Ph.D.
2011 New Investigator Research Grant
The hippocampus, a brain region important for learning and memory, is one of the most vulnerable regions in early Alzheimer's disease. People with early Alzheimer's tend to suffer losses of hippocampal volume, a brain change that can be seen on magnetic resonance imaging (MRI) brain scans. Yet hippocampal shrinkage is not a sufficiently sensitive biomarker for diagnosing people in the earliest stages of disease. Recently, scientists have developed more sophisticated MRI methods that may detect early disease-related changes within the hippocampus —-changes that occur before overall hippocampal shrinkage takes place.
In preliminary research with human volunteers, Geoffrey A. Kerchner, M.D., Ph.D., and colleagues tested a new MRI procedure called ultra-high field 7-Tesla (7T) MRI. This high-resolution technique produced images that detected cellular-level changes in a region of the hippocampus called the cornu ammonis 1 (CA1). The images showed shrinkage of the dendrites, or branchlike projections, of CA1 nerve cells. Such projections are involved in cell-to-cell communication processes, and their shrinkage was likely caused by accumulations of abnormal tau protein, a key suspect in Alzheimer's disease. Dendritic shrinkage may induce cell-to-cell communication problems in the brain and lead to neuronal losses in the hippocampus. Dr. Kerchner's team found that levels of CA1 shrinkage were a sensitive biomarker for separating people with early Alzheimer's disease from cognitively normal people.
For this study, the researchers will build on their earlier research. They will recruit human volunteers with mild cognitive impairment (MCI), a condition that often precedes Alzheimer's. The participants will receive 7T MRI scans, and their cerebrospinal fluid (the fluid that surrounds the brain) will be tested for abnormal levels of tau and of beta-amyloid, another molecular suspect in Alzheimer's disease. The investigators will then monitor their participants' cognitive health over several years. Dr. Kerchner's group hopes to show that the combination of cerebrospinal fluid testing and 7T MRI assessments can provide an optimal way of diagnosing an individual's risk of progressing from MCI to dementia.