IC-P-033: Adult children of AD parent have smaller hippocampal volumes

Abstract

In previous MR studies of very mild dementia of the Alzheimer type (DAT), we reported smaller hippocampal volumes and deformities of the hippocampal surface zones corresponding to underlying CA1 and subiculum subfields. This finding suggests that irregularities of hippocampal volume and surface shape distinguish subjects with early DAT from nondemented subjects, but the degree to which such findings represent early form degeneration or a long–standing “anatomic” vulnerability to disease is unknown. We assessed the volume and shape of the hippocampus in the middle–aged, adult children of parents with DAT and age–matched controls. We hypothesized that measures of smaller hippocampal volume and an inward shape deformity of the hippocampal surface corresponding to the CA1 and subiculum subfields would discriminate the two groups of subjects. MR scans of 35 adult children with a biologic parent with DAT with 39 control subjects were included in this study. Nineteen control subjects came from ADRC ACS sample of subjects with biologic parents without DAT, and 20 age and gender matched additional controls came from our schizophrenia study without a family history of AD (Table 1). Large–deformation high–dimensional brain mapping was applied to all scans to generate hippocampal surfaces from the template in each subject scan. An average hippocampal surface constructed from 86 healthy subjects from a previous study was used as a reference. For each subject in this study, displacements from this reference were computed for all surfaces. Mean displacements for each zone are computed for each subject as shape measures. Volume and shape measures for the two groups of subjects are summarized in Table 2. There was a significant group effect (F=5.4, df=1.72, p=0.022) in hippocampal volume. After adjusting for multiple comparisons, significant group differences were found in the inferior–medial and superior zones, but not the lateral zone. This result suggests that the middle–aged children (45–65 years of age) of subjects with DAT have smaller hippocampal volumes as compared to the children of healthy non–demented subjects matched for age. This finding supports the hypothesis that there is a long–standing relationship between smaller hippocampal volumes and increased risk of developing Alzheimer's disease (AD). P01–AG026276, P01–AG03991, P50–AG05681, R01–MH60883, R01–MH56584, P41–RR15241.