IC-P2-150: Comparing rates of change versus cross-sectional hippocampal measure in early DAT

Abstract

Background: In cross-sectional studies comparing subjects with and without very mild dementia of the Alzheimer type (DAT), we showed that deformities of hippocampal surface shape and volume could discriminate groups. While this suggests that irregularities of hippocampal structure are a feature of early AD, they could represent an early form of neurodegeneration or a long-standing “anatomic” vulnerability to disease. In this study, we compared the volume and shape of the hippocampus over time in very mildly demented and nondemented subjects, and determined whether the rate of changes in structural measures would improve the discrimination of subject groups based on cross-sectional (baseline) measures. Methods: MR scans were collected from 54 CDR 0.5 subjects and 69 CDR 0 subjects on multiple occasions (Table 1). Large-deformation high-dimensional brain mapping was applied to all scans to generate hippocampal surfaces in each subject scan. An average hippocampal surface constructed from 86 healthy subjects from a previous study was used as a reference to compute displacements from this reference for all surfaces. Mean displacements for hippocampal surface zones corresponding to the CA1, subiculum and remainder subfields were computed for each subject as shape measures. Mixed models with baseline CDR status as fixed factor and between-scan interval as random factor were used to test for group differences in rates of change in the hippocampal variables. Gender was used as a covariate. Results: At baseline, CDR 0.5 subjects had smaller volumes and more inwardly deformed hippocampal surfaces as compared with CDR 0 subjects. In particular, the surface zone associated with the CA1 hippocampal subfield deformed inwardly at a faster rate in the CDR 0.5 subjects than in the CDR 0 subjects. However, the effect size of the longitudinal comparison was smaller than the effect size of the cross-sectional comparison at baseline. See Table 2. Conclusions: These results suggest that while very mild DAT subjects show a more rapid rate of hippocampal volume loss and shape deformation than nondemented subjects, the degree of hippocampal deformation at the onset of dementia is already substantial and is as good or better than measures of changes in structure for group discrimination. P01-AG026276,P01-AG03991, P50-AG05681,R01-MH60883, R01-MH56584,P41-RR15241.