Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease

Abstract

Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly control subjects and AD patients with the very mildest form of the disease. We performed MRI-based volumetric measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly control subjects and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR 0.5 were classified as very mild, CDR 1 as mild, and CDR 2 as moderate disease severity. Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (p < 0.001). Of the several MTL measures, the total hippocampal volumetric measurements were best at discriminating control subjects from AD patients. The mean hippocampal volumes for AD patients relative to control subjects by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD. Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.

Figure 1. Neuroanatomic Boundaries

Two columns of images are presented. On the left, cropped oblique coronal MR images through the temporal lobes of a 75 year-old female control, and on the right images from a 73-year-old female AD patient, CDR = 1. In each column, 3 images are present. From the top to bottom, these represent sections at the level of the hippocampal tail, hippocampal body, and hippocampal head. The anatomic outlines of the hippocampus, and PHG are indicated on images of the hippocampal head, and hippocampal body. The outline of the amygdala and hippocampus are indicated in the bottom image of the hippocampal head. Neuroanatomic criteria employed when tracing the boundaries of these 3 MTL structures are indicated in the text.

Figure 2. Normalized Hippocampal Volume by Age in Control Subjects and AD Patients

Regression of the mean normalized hippocampal volume by age in male (A) and female (B) control subjects and AD patients. The upper and lower limits dashed lines, represent the 75th and 25th percentile values for each group. Hippocampal volumes of AD patients are smaller than those of age matched controls. Volumes in both groups decline linearly and in parallel with advancing age. For clinical purposes the position of a memory impaired elderly subject may be plotted and compared to age and gender matched controls and AD patients.