Preclinical Alzheimer's Disease in the Entorhinal and Transentorhinal Cortex

Research on biomarkers of Alzheimer's disease has been shifting focus toward identifying changes in the preclinical stage, a stage prior to the emergence of cognitive deficits. Advances in the field of computational anatomy leverages noisy, longitudinal data for more sensitive and robust detection of shape differences. In particular, cortical thickness measures have been shown to be a sensitive marker of change. In this work, we introduce a pipeline for quantifying cortical thickness and develop three models to study the earliest changes detected from structural MRI. First, we investigate where grey matter atrophy occurs with great spatial resolution using a new cortical thickness metric and a mixed effects model of group differences. Next, we determine when grey matter atrophy begins using a piece-wise linear mixed effects model of atrophy. Finally, we characterize early progression of the disease in an individual using a subject-specific model of atrophy spread

Preclinical Alzheimer's Disease in the Entorhinal and Transentorhinal Cortex

Research on biomarkers of Alzheimer's disease has been shifting focus toward identifying changes in the preclinical stage, a stage prior to the emergence of cognitive deficits. Advances in the field of computational anatomy leverages noisy, longitudinal data for more sensitive and robust detection of shape differences. In particular, cortical thickness measures have been shown to be a sensitive marker of change. In this work, we introduce a pipeline for quantifying cortical thickness and develop three models to study the earliest changes detected from structural MRI. First, we investigate where grey matter atrophy occurs with great spatial resolution using a new cortical thickness metric and a mixed effects model of group differences. Next, we determine when grey matter atrophy begins using a piece-wise linear mixed effects model of atrophy. Finally, we characterize early progression of the disease in an individual using a subject-specific model of atrophy spread

Cortical thickness atrophy in the transentorhinal cortex in mild cognitive impairment.

This study examines the atrophy rates of subjects with mild cognitive impairment (MCI) compared to controls in four regions within the medial temporal lobe: the transentorhinal cortex (TEC), entorhinal cortex (ERC), hippocampus, and amygdala. These regions were manually segmented and then corrected for undesirable longitudinal variability via Large Deformation Diffeomorphic Metric Mapping (LDDMM) based longitudinal diffeomorphometry. Diffeomorphometry techniques were used to compare thickness measurements in the TEC with the ERC. There were more significant changes in thickness atrophy rate in the TEC than medial regions of the entorhinal cortex. Volume measures were also calculated for all four regions. Classifiers were constructed using linear discriminant analysis to demonstrate that average thickness and atrophy rate of TEC together was the most discriminating measure compared to the thickness and volume measures in the areas examined, in differentiating MCI from controls. These findings are consistent with autopsy findings demonstrating that initial neuronal changes are found in TEC before spreading more medially in the ERC and to other regions in the medial temporal lobe. These findings suggest that the TEC thickness could serve as a biomarker for Alzheimer's disease in the prodromal phase of the disease

Cortical thickness atrophy in the transentorhinal cortex in mild cognitive impairment

This study examines the atrophy rates of subjects with mild cognitive impairment (MCI) compared to controls in four regions within the medial temporal lobe: the transentorhinal cortex (TEC), entorhinal cortex (ERC), hippocampus, and amygdala. These regions were manually segmented and then corrected for undesirable longitudinal variability via Large Deformation Diffeomorphic Metric Mapping (LDDMM) based longitudinal diffeomorphometry. Diffeomorphometry techniques were used to compare thickness measurements in the TEC with the ERC. There were more significant changes in thickness atrophy rate in the TEC than medial regions of the entorhinal cortex. Volume measures were also calculated for all four regions. Classifiers were constructed using linear discriminant analysis to demonstrate that average thickness and atrophy rate of TEC together was the most discriminating measure compared to the thickness and volume measures in the areas examined, in differentiating MCI from controls. These findings are consistent with autopsy findings demonstrating that initial neuronal changes are found in TEC before spreading more medially in the ERC and to other regions in the medial temporal lobe. These findings suggest that the TEC thickness could serve as a biomarker for Alzheimer's disease in the prodromal phase of the disease. Keywords: Entorhinal cortex, Transentorhinal cortex, Mild cognitive impairment, Braak staging, Cortical thickness, Shape analysis, Longitudinal analysi