Entorhinal and Transentorhinal Atrophy in Preclinical Alzheimer's Disease

Abstract

This study examines the atrophy patterns in the entorhinal and transentorhinal cortices of subjects that converted from normal cognition to mild cognitive impairment. The regions were manually segmented from 3T MRI, then corrected for variability in boundary definition over time using an automated approach called longitudinal diffeomorphometry. Cortical thickness was calculated by deforming the gray matter-white matter boundary surface to the pial surface using an approach called normal geodesic flow. The surface was parcellated based on four atlases using large deformation diffeomorphic metric mapping. Average cortical thickness was calculated for (1) manually-defined entorhinal cortex, and (2) manually-defined transentorhinal cortex. Group-wise difference analysis was applied to determine where atrophy occurred, and change point analysis was applied to determine when atrophy started to occur. The results showed that by the time a diagnosis of mild cognitive impairment is made, the transentorhinal cortex and entorhinal cortex was up to 0.6 mm thinner than a control with normal cognition. A change point in atrophy rate was detected in the transentorhinal cortex 9–14 years prior to a diagnosis of mild cognitive impairment, and in the entorhinal cortex 8–11 years prior. The findings are consistent with autopsy findings that demonstrate neuronal changes in the transentorhinal cortex before the entorhinal cortex.

Reaction-Diffusion Model of Cortical Atrophy Spread during Early Stages of Alzheimer’s Disease

“…The origin of atrophy was also consistently found in the anterior lateral region of the rhinal cortex. This is in line with our previous population-wise studies that showed atrophy of preclinical subjects in the lateral region of the rhinal cortex, and more atrophy in the anterior region than the posterior region [11].…”

“…The disease stage at the final scan time in the three case studies suggest more than 32% atrophy occurred in the anterior lateral region of the rhinal cortex prior to a diagnosis of MCI. This is more atrophy than our population study of preclinical subjects showed, where the disease model had a maximum atrophy of 17% at the time of MCI diagnosis [11]. One possible explanation for this discrepancy may be that population-wise studies attribute some disease-related atrophy to individual variability in cortical thickness, since no prior is available on an individual basis of differences in thickness.…”

“…This is important because disease-related atrophy is thought to begin 8 to 10 years prior to symptom onset. The shape of the cortex at the first scan is a reasonable approximation of the cortical thickness prior to disease-related atrophy for these subjects [24], [11].…”

“…To calculate cortical thickness, we used previously established methods [11] and briefly summarize the methods here. We followed a landmark-based protocol for manual segmentation of the left ERC and TEC.…”

“…There is evidence that AD-related atrophy begins 8 to 10 years prior to symptom onset in the entorhinal cortex (ERC), and 2 to 4 years prior to symptom onset in the hippocampus [24]. Our recent work has further suggested that disease-related atrophy begins in the transentorhinal cortex (TEC) before the ERC [11]. This pattern of atrophy mirrors the accumulation of neurofibrillary tau tangles, which has been used to stage Alzheimer’s disease post-mortem [3].…”