Lateral entorhinal cortex dysfunction in amnestic mild cognitive impairment

The entorhinal cortex is the site of some of the earliest pathological changes in Alzheimer's disease, including neuronal, synaptic and volumetric loss. Specifically, the lateral entorhinal cortex shows significant accumulation of tau neurofibrillary tangles in the amnestic mild cognitive impairment (aMCI) phase of Alzheimer's disease. Although decreased entorhinal cortex activation has been observed in patients with aMCI in the context of impaired memory function, it remains unclear if functional changes in the entorhinal cortex can be localized to the lateral or medial entorhinal cortex. To assess subregion specific changes in the lateral and medial entorhinal cortex, patients with aMCI and healthy aged-matched control participants underwent high-resolution structural and functional magnetic resonance imaging. Patients with aMCI showed significantly reduced volume, and decreased activation localized to the lateral entorhinal cortex but not the medial entorhinal cortex. These results show that structural and functional changes associated with impaired memory function differentially engage the lateral entorhinal cortex in patients with aMCI, consistent with the locus of early disease related pathology.