Rate of entorhinal and hippocampal atrophy in incipient and mild AD: relation to memory function

Abstract

In the present study, as part of a more extensive longitudinal investigation of the in vivo anatomical markers of early and incipient AD in our laboratory, three groups of elderly participants were followed with yearly clinical evaluations and high resolution MRI scans over a 6-year period (baseline and 5 years of follow-up). At baseline, participants consisted of: (1) 35 old subjects with no cognitive impairment (controls); (2) 33 participants with amnestic mild cognitive impairment (MCI); and (3) 14 patients with very mild AD. 11 participants with amnestic MCI received a diagnosis of AD over the follow-up period and 9 controls declined in cognitive function. T1 weighted MRI scans were acquired using a 3D SPGR pulse sequence. At baseline, both the amnestic MCI and mild AD groups differed from the controls in hippocampal and entorhinal cortex volume, but not from each other. Longitudinal analyses showed that the rate of atrophy of the entorhinal cortex and hippocampus for the stable controls differed significantly from MCI participants who converted to AD and the AD groups. Furthermore, longitudinal decreases in hippocampal and entorhinal volume were related to longitudinal decline in declarative memory performance. These findings suggest that the rate of atrophy of mesial temporal lobe structures can differentiate healthy from pathological aging.

Fig. 1

A single coronal slice illustrating the segmentation of the entorhinal cortex (right hand side of the image) and the hippocampal formation (left hand side of the image). The right hand side of the image corresponds to the left hemisphere and vice versa.

Fig. 2

(A) Mean normalized entorhinal and hippocampal volumes (absolute volume in mm³/intracranial volume in mm³ × 1000) at baseline for elderly control subjects (NCI), patients with amnestic mild cognitive impairment (MCI) and those with very mild AD (A). Panels in (B) show baseline entorhinal an hippocampal volumes for control participants who remained stable during the follow-up period (NCI-S), controls who declined in cognitive function (NCI-D), MCI participants who remained stable (MCI-S), people with MCI who received a diagnosis of AD during the follow-up (MCI-AD), and the group that was diagnosed with mild AD at entry into the study. The values for each region of interest are based on the sum of right and left hemisphere volumes. Vertical bars represent the standard error of the mean. *Significantly different from NCI-S, p < 0.001; †significantly different from NCI-D, p = 0.03 for EC and p = 0.005 for hippocampus; ‡significantly different from MCI-S, p = 0.013.

Fig. 3

Mean normalized entorhinal cortex and hippocampal volumes at baseline and over the 5 years of follow-up for the five groups described in Fig. 2B (left hand panels). The slopes shown are modeled linear slopes. Vertical bars represent the standard error of the mean. In the right hand panels, the same baseline starting point was used for all groups to better appreciate differences in slope.

Fig. 4

The relation between memory z-scores (vertical axis) and z-scores based on normalized entorhinal cortex and hippocampal volumes (horizontal axis) plotted for each individual participant over time. The arrowhead shows the direction of time, and points from the baseline exam towards the last exam for any given participant. The diagnosis at the first and the last exam are shown as symbols indicated in the legend of the figure.