MRI hippocampal and entorhinal cortex mapping in predicting conversion to Alzheimer's disease.

OBJECTIVE

Using MRI surface morphometry mapping, to evaluate local deformations of the hippocampus, parahippocampal gyrus, and entorhinal cortex in predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD).

METHODS

Baseline brain MRI with surface morphological analysis was performed in 130 outpatients with MCI, broadly defined, and 61 healthy controls followed for an average of 4 years in a single site study.

RESULTS

Patients with MCI differed from controls in several regions of the hippocampus and entorhinal cortex, and to a lesser extent in the parahippocampal gyrus. In the MCI sample, Cox regression models were conducted for time to conversion comparing converters to AD (n=31) and non-converters (n=99), controlling for age, sex and education. Converters showed greater atrophy in the head of the hippocampus, predominantly in the CA1 region and subiculum, and in the entorhinal cortex, especially in the anterior-inferior pole bilaterally. When distances of specific points representing localized inward deformation were entered together with the corresponding hippocampal or entorhinal cortex volume in the same Cox regression model, the distances remained highly significant whereas the volumes of the corresponding structures were either marginally significant or not significant. Inclusion of cognitive or memory measures or apolipoprotein E ε4 genotype as covariates, or restricting the sample to patients with amnestic MCI (24 converters and 81 non-converters) did not materially change the findings. In the 3-year follow-up sample of patients with MCI, logistic regression analyses using the same measures and covariates yielded similar results.

INTERPRETATION

These findings indicate selective early involvement of the CA1 and subiculum regions of the hippocampus and provide new information on early anterior pole involvement in the entorhinal cortex in incipient AD. Fine-grained surface morphometry of medial temporal lobe structures may be superior to volumetric assessment in predicting conversion to AD in patients clinically diagnosed with MCI.