Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer Disease

Abstract

Alzheimer disease (AD) is the most common type of dementia worldwide. Hippocampal atrophy and ventricular enlargement have been associated with AD but also with normal aging. We analyzed 1.5-T brain magnetic resonance imaging data from 46 cognitively normal elderly individuals (NC), 33 mild cognitive impairment and 43 AD patients. Hippocampal and ventricular analyses were conducted with 2 novel semiautomated segmentation approaches followed by the radial distance mapping technique. Multiple linear regression was used to assess the effects of age and diagnosis on hippocampal and ventricular volumes and radial distance. In addition, 3-dimensional map correction for multiple comparisons was made with permutation testing. As expected, most significant hippocampal atrophy and ventricular enlargement were seen in the AD versus NC comparison. Mild cognitive impairment patients showed intermediate levels of hippocampal atrophy and ventricular enlargement. Significant effects of age on hippocampal volume and radial distance were seen in the pooled sample and in the NC and AD groups considered separately. Age-associated differences were detected in all hippocampal subfields and in the frontal and body/occipital horn portions of the lateral ventricles. Aging affects both the hippocampus and lateral ventricles independent of AD pathology, and should be included as covariate in all structural, hippocampal, and ventricular analyses when possible.

Figure 1

Box plot of the age-, gender- and education-normalized hippocampal and ventricular volumes in NC, MCI and AD. The central box displays the data between the upper and lower quartiles with the line representing the median and the cross representing the mean. The “whiskers” display the range for the upper and lower quartiles, resp. The feet of the whiskers represent the full range of each variable.

Figure 2

3D hippocampal between-group statistical (left) and quantitative (right) comparisons. The statistical maps are corrected for age, sex and education.

Figure 3

Effect of age on hippocampal radial distance while controlling for diagnosis, sex and education in the pooled sample and in each diagnostic group while controlling for gender and education.

Figure 4

3D ventricular between-group statistical (left) and quantitative (right) comparisons. The statistical maps are corrected for age, sex and education.

Figure 5

Effect of age on hippocampal radial distance while controlling for diagnosis, gender and education in the pooled sample and in each diagnostic group while controlling for gender and education.