Entorhinal and Transentorhinal Atrophy in Preclinical Alzheimer's Disease.

Sue Kulason,Marilyn Albert,Michael I Miller,Eileen Xu,Daniel J Tward,Laurent Younes,Arnold Bakker

doi:10.3389/fnins.2020.00804

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.

Highlights

Evidence suggests that neuropathological changes of Alzheimer’s disease (AD) begin years before the onset of clinical symptoms (Sperling et al, 2011)
The first major finding of this study is that anterior regions of the entorhinal cortex (ERC) and transentorhinal cortex (TEC) were more than half a millimeter thinner in normal cognition (NC) to mild cognitive impairment (MCI) converters at the time of MCI diagnosis, and that disease-related atrophy was roughly 3% per year
The evidence suggests that disease-related atrophy begins prior to an MCI diagnosis in the anterior lateral region of ERC and anterior region of TEC

Summary

Introduction

Evidence suggests that neuropathological changes of Alzheimer’s disease (AD) begin years before the onset of clinical symptoms (Sperling et al, 2011). More recent MRI studies have focused on evidence of atrophy that precede clinical symptoms (Jack et al, 2004; Csernansky et al, 2005; den Heijer et al, 2006; Apostolova et al, 2010; Dickerson et al, 2011; Miller et al, 2013; Soldan et al, 2015; Pettigrew et al, 2016), often detecting these smaller changes using time-series data analysis (Durrleman et al, 2012) and survival analysis. Our group’s work on change point analysis has demonstrated MRI-based shape metrics can detect atrophy in the ERC earlier than hippocampal and amygdalar atrophy (Younes et al, 2014) These changes precede clinical symptoms by up to 10 years

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