Abstract

IntroductionLoss 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).MethodsWe 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.ResultsGroup 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.DiscussionThinning 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.

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