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Anterolateral entorhinal cortex thickness as a new biomarker for early detection of Alzheimer's disease.

ABSTRACT: Introduction:Loss of entorhinal cortex (EC) layer II neurons represents the earliest Alzheimer's disease (AD) lesion in the brain. Research suggests differing functional roles between two EC subregions, the anterolateral EC (aLEC) and the posteromedial EC (pMEC). Methods:We use joint label fusion to obtain aLEC and pMEC cortical thickness measurements from serial magnetic resonance imaging scans of 775 ADNI-1 participants (219 healthy; 380 mild cognitive impairment; 176 AD) and use linear mixed-effects models to analyze longitudinal associations among cortical thickness, disease status, and cognitive measures. Results:Group status is reliably predicted by aLEC thickness, which also exhibits greater associations with cognitive outcomes than does pMEC thickness. Change in aLEC thickness is also associated with cerebrospinal fluid amyloid and tau levels. Discussion:Thinning of aLEC is a sensitive structural biomarker that changes over short durations in the course of AD and tracks disease severity-it is a strong candidate biomarker for detection of early AD.

SUBMITTER: Holbrook AJ

PROVIDER: S-EPMC7447874 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Anterolateral entorhinal cortex thickness as a new biomarker for early detection of Alzheimer's disease.

Holbrook Andrew J AJ Tustison Nicholas J NJ Marquez Freddie F Roberts Jared J Yassa Michael A MA Gillen Daniel L DL

Alzheimer's & dementia (Amsterdam, Netherlands) 20200825 1

<h4>Introduction</h4>Loss of entorhinal cortex (EC) layer II neurons represents the earliest Alzheimer's disease (AD) lesion in the brain. Research suggests differing functional roles between two EC subregions, the anterolateral EC (aLEC) and the posteromedial EC (pMEC).<h4>Methods</h4>We use joint label fusion to obtain aLEC and pMEC cortical thickness measurements from serial magnetic resonance imaging scans of 775 ADNI-1 participants (219 healthy; 380 mild cognitive impairment; 176 AD) and us ...[more]

PMID: 32875052

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Project description:ObjectiveUsing 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).MethodsBaseline 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.ResultsPatients 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 ?4 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.InterpretationThese 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.

Dataset Information

Anterolateral entorhinal cortex thickness as a new biomarker for early detection of Alzheimer's disease.

Publications

Anterolateral entorhinal cortex thickness as a new biomarker for early detection of Alzheimer's disease.

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