Evaluating the function of hippocampal subregions with high-resolution MRI in Alzheimer's disease and aging

Memory ability declines in older age groups. There is a growing list of physiological processes that target the hippocampal formation in an age-related fashion, and some might underlie the hippocampal component of memory decline. The hippocampal formation is comprised of separate subregions, and physiological processes differentially target these subregions. The ability to evaluate the functional integrity of individual subregions-performing subregional analysis-is a major clinical goal since it can aid in the diagnosis of memory decline, as well as in elucidating mechanisms of disease and testing potential interventions. Because of its superior spatial resolution, magnetic resonance imaging (MRI) is best suited to accomplish this goal. Despite limited success, most functional MRI (fMRI) protocols have difficulty in performing complete subregional analysis of the hippocampal formation. Here we address sources of difficulty by (1) generating T2* -weighted maps of the hippocampal formation with sub-millimeter resolution; and (2) by adapting an approach used by animal investigators to identify the hippocampal subregions using anatomical landmarks. The protocol is tested in patients with Alzheimer's disease and in healthy controls, in an effort to determine whether it can detect neuronal dysfunction. Results showed diminished signal in the hippocampal formation of patients with Alzheimer's disease (AD) compared to controls, and multivariate analysis showed that this difference was most prominent in the entorhinal cortex. The protocol can be used to perform subregional analysis of the hippocampal formation. Testing the protocol in other clinical populations is needed to demonstrate its efficacy in evaluating the neuronal integrity of all hippocampal subregions.