MICROGLIAL ACTIVATION IS ASSOCIATED WITH HIGHER GREY MATTER DENSITY AND HIPPOCAMPAL VOLUME IN MCI SUBJECTS

Abstract

Amyloid and neurofibrillary tangles are characteristic features of Alzheimer's disease (AD), and microglial activation has been proposed to be the link between amyloid deposition, tangle formation and neuronal damage. However, the role of microglial activation in early stages of AD trajectory is still being debated. In this study, we evaluated the in vivo relationship between microglial activation, grey matter density and hippocampal volume in mild cognitive impairment (MCI). Thirty (21 MCI and nine control) subjects underwent [11C]PBR28 PET scan, a marker of microglial activation; volumetric MRI scan to assess grey matter density and hippocampal volume; [18F]Flutemetamol PET scans to assess amyloid load, along with neurological and neuropsychometric evaluation. [11C]PBR28 VT (distribution volumes) was calculated using arterial input function. Grey matter density and hippocampal volumes were calculated from T1 volumetric MRI scans. Voxel-wise correlations and biological parametric mapping (BPM) analysis were performed using Statistical parametric mapping software (SPM8). Amyloid load was calculated using 90–120 minute target region:cerebellar uptake ratios. Region of interest analysis was also done for [11C]PBR28 and [18F]Flutemetamol PET. [11C]PBR28 VT in different cortical areas were positively correlated with hippocampal volume and tests of immediate and delayed recall. Significant positive correlations were demonstrated between [11C]PBR28 VT and grey matter density. In this study, we report for the first time that increased [11C]PBR28 VT was associated with higher grey matter density, higher hippocampal volume and better cognitive performance. These findings have huge implications on novel therapeutic strategies influencing microglial activation in Alzheimer's and other diseases.