LATERAL ENTORHINAL CORTEX HYPOACTIVATION IN AMNESTIC MILD COGNITIVE IMPAIRMENT

Abstract

Increased hippocampal activation in the context of impaired memory function is considered a characteristic feature of the amnestic mild cognitive impairment (aMCI) phase of Alzheimer’s disease. However, the entorhinal cortex, which serves as the primary relay for both input and output to and from the hippocampus, is the site of the earliest pathological changes including neuronal, synaptic and volume loss. Specifically, the lateral entorhinal cortex is also the site of significant accumulation of tau neurofibrillary tangles early in the disease progression. To assess whether functional changes can be observed in the lateral and medial entorhinal cortex in patients with aMCI, 37 healthy older adults and 42 patients with aMCI completed a forced choice memory task designed to tax medial temporal lobe memory function while completing a high-resolution functional magnetic resonance imaging (fMRI) scan. Consistent with their diagnosis and previous studies, patients with aMCI showed a significant memory impairment compared to age-matched healthy control subjects as well as increased hippocampal activation. In this context, patients with aMCI also showed significantly decreased activation in both the left and right entorhinal cortex. The observed hypoactivation was localized to the lateral entorhinal cortex and was not observed in the medial entorhinal cortex. Decreased activation in the left lateral entorhinal cortex was correlated with poorer performance on the memory task in patients with aMCI. Finally, the volume of both the left and right lateral entorhinal cortex was significantly reduced in patients with aMCI compared to healthy control subjects while no volume differences between the groups were observed in the medial entorhinal cortex. These results show that, consistent with the locus of early disease related pathology, decreased activation and reduced volume in specifically the lateral entorhinal cortex is observed in patients with aMCI and is associated with impaired memory function in these patients.