Patients with Amyloid-Negative Mild Cognitive Impairment have Cortical Hypometabolism but the Hippocampus is Preserved.

Abstract

Patients with mild cognitive impairment (MCI) are at risk for Alzheimer's dementia but the presence of amyloid (Aβ) strongly increases this risk. In clinical settings, when Aβ status is not available, different neurodegenerative markers are used to characterize MCI. The accuracy of these markers to discriminate between Aβ-and Aβ+ MCI is not yet determined. To compare different markers of neurodegeneration in Aβ-and Aβ+ MCI, with an Aβ-elderly control (EC) group. Patients with MCI (n = 39) and EC (n = 28) underwent MRI, 18F-FDG PET, and Aβ PET (18F-flutemetamol). We compared FDG and MRI biomarker values in cortical and hippocampal regions of interest, and using voxel-wise surface maps. We computed ROC curves discriminating between the three groups for each biomarker. All biomarker values were reduced in Aβ+ MCI compared to EC (p < 0.001). Aβ-MCI had low cortical metabolism (p = 0.002), but hippocampal volume, cortical thickness, and hippocampal metabolism were not significantly different between Aβ-MCI and EC (p > 0.40). Cortical metabolism best discriminated between MCI and EC (AUC = 0.92/0.86, Aβ+/Aβ-) while hippocampal volume best discriminated between Aβ-MCI and Aβ+ MCI (AUC = 0.79). Cortical hypometabolism was observed in both Aβ-MCI and Aβ+ MCI whereas hippocampal atrophy was mostly found in Aβ+ MCI. For MCI patients without available Aβ information, hippocampal atrophy is thus more informative about Aβ status than cortical hypometabolism.