Abstract

Normal aging and Alzheimer's disease (AD) are both associated with loss of hippocampal neurons. However, histological studies suggest that hippocampal neuronal loss is different in normal aging and AD. While in AD neuron loss is most pronounced in CA1, normal aging is thought to predominantely impact the hilus and subiculum, although this is controversal. The aims of this study were: 1. To test if hippocampal subfields can be identified and reliably traced using anatomical landmarks on MR images with submillimeter resolution. 2. To test if age-related volume changes of subfields can be detected. 14 subjects (12 healthy controls mean age 47.3, range: 24-77 years werestudied on a 4T system with using a T2 weighted high resolution turbo-spin-echo sequence (TR/TE: 3500/19 ms, turbofactor 15, 18.6 ms echo spacing, 160° flip angle, FOV 200, 512x384 matrix, 2 mm slice thickness, 24, interleaved slices without gap). Using anatomical landmarks, entorhinal cortex (ERC), subiculum, CA1, CA2 and CA3/dentate compound (CA3, CA4, dentate gyrus) on both sides were traced twice by two raters. Intraclass correlation coefficients (ICC) were calculated to assess reliablity of markings within and between raters. The mean ICC for rater 1 was 0.96 (range 0.83- 0.99) and for rater 2 the mean ICC was 0.87 (range 0.66-0.98).The between rater ICC for the different subfields ranged between 0.67 and 0.93 and was above 0.87 for the CA1 sectors In the group of healthy subjects, there was a significant correlation between age and the left and right CA1 (left: r= -0.63, p=0.02; right: r= -0.53, p=0.04). These preliminary results suggest that it is possible to reliably identify and mark hippocampal subfields on high resolution MRIs of the hippocampus. The major finding was a significant correlation between age and the CA1 but not other subfields. This contrasts with some histological data suggesting that age is primarily associated with atrophy of the hilus and subiculum. Further studies on a larger group of subjects are needed to assess the changes in hippocampal subfields in normal aging and AD and to determine the value of these measurements for the early detection of AD.

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