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From the Alzheimer’s Disease Research Center and the Departments of Psychiatry (Drs. Csernansky and Wang), Neurology (Dr. Morris), Anatomy and Neurobiology (Dr. Csernansky), Radiology (Drs. Gado and Kido), Pathology (Drs. McKeel and Morris), and the Division of Biostatistics (J.P. Miller), Washington University School of Medicine, St. Louis, MO; the Center for Imaging Science (Dr. M.I. Miller), Whiting School of Engineering at Johns Hopkins University, Baltimore, MD; and Departments of Radiation Oncology and Biomedical Engineering (Dr. Joshi), University of North Carolina at Chapel Hill.
Address correspondence and reprint requests to Dr. John G. Csernansky, Department of Psychiatry (Box 8134), Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110; e-mail: csernanj{at}medicine.wustl.edu
Article abstract—
OBJECTIVE: To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects.
BACKGROUND: HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus.
METHODS: MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups.
RESULTS: Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss.
CONCLUSIONS: Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.
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