Hippocampal shape analysis in Alzheimer's disease: A population-based study

Background. Hippocampal atrophy - particularly of the CA1 region may be useful as a biomarker for Alzheimer's disease (AD) or the risk for AD. The extent to which the AD hippocampus can be distinguished in vivo from changes due to normal aging or other processes that affect the hippocampus is of clinical importance and is an area of active research. In this study, we use structural imaging techniques to model hippocampal size and regional shape differences between elderly men with incident AD and a non-demented comparison group of elderly men. Methods: Participants are Japanese-American men from the Honolulu Asia Aging Study (HAAS). The HAAS cohort has been followed since 1965. The following analysis is based on a sub-group of men who underwent MRI examination in 1994-1996. Participants were diagnosed with incident AD (n = 24: age= 82.5 +/-:4.6) or were not demented (n = 102: age = 83.0 +/- 5.9). One reader, blinded to dementia diagnosis, manually outlined the left and right hippocampal formation using published criteria. We used 3D structural shape analysis methods developed at the Laboratory of Neuro Imaging (LONI) to compare regional variation in hippocampal diameter between the AD cases and the non-demented comparison group. Results: Mean total hippocampal volume was 11.5% smaller in the AD cases than the non-demented controls (4903 +/- 857 mm(3) vs. 5540 +/- 805 mm(3)), with a similar size difference for the median left (12.0%) and median right (11.6%) hippocampus. Shape analysis showed a regional pattern of shape difference between the AD and nondemented hippocampus, more evident for the hippocampal body than the head, and the appearance of more consistent differences in the left hippocampus than the right. While assignment to a specific sub-region is not possible with this method, the surface changes primarily intersect the area of the hippocampus body containing the CA1 region (and adjacent CA2 and distal CA3), subiculum, and the dentate gyrus-hilar region. (C) 2006 Elsevier Inc. All rights reserved.