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

Alzheimer s 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 1.5T brain MRI data from 46 cognitively normal elderly (NC), 33 mild cognitive impairment (MCI) and 43 AD subjects. Hippocampal and ventricular analyses were conducted with two novel semi-automated segmentation approaches followed by the radial distance mapping technique. Multiple linear regression was used to assess effects of age and diagnosis on hippocampal and ventricular volumes and radial distance. Additional 3D map correction for multiple comparisons was conducted with permutation testing. As expected, most significant hippocampal atrophy and ventricular enlargement were seen in the AD vs. NC comparison. MCI subjects 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 as well as in the NC and AD groups considered separately. Age-associated differences were detected in all hippocampal subfields and 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.