Colocalization of cortical diffusivity changes and microglial activation in dementia

Abstract

AbstractBackgroundThere is growing evidence that microglial activation plays a crucial role in the early pathological changes reported in Alzheimer’s disease (AD). Multimodal neuroimaging can be used to detect micro‐ and macrostructural alterations together with molecular imaging to quantify metabolism and proteins expression. Diffusivity map, reflecting neuronal integrity, can be derived from diffusion‐weighted imaging, and is thought to be increased in AD following pathological alterations. We hypothesised that changes in diffusivity could be colocalized with microglial activation at different stages of the disease.Method56 patients (mean age=70.4, SD=8.5) cognitively normal (CN, n=15), with mild cognitive impairment (MCI, n=28) and with AD (n=12) were included in this study. All participants underwent diffusion tensor imaging (DTI), amyloid PET ([18F]flutemetamol) and TSPO PET ([11C]PBR28). DTI data were processed with FSL v.6.0 to compute mean diffusivity (MD) maps. Standard uptake ratio (SUVR) values were calculated in SPM12 to identify the amyloid deposition and microglial activation within cortical regions. Amyloid status (Aβ‐positive/Aβ‐negative) was determined from processed data using a cerebellar gray matter ratio with a binding value greater than the CN mean+2SD. Z score maps of MD and [11C]PBR28 SUVR were computed using CN amyloid negative participants as reference. Z score maps were then correlated using SPM8 and the BPM toolbox. Significance was set at a threshold of p<0.05 with an extended threshold of 50 voxels.ResultWe found a significant positive correlation clusters between MD and PBR28‐SUVR Z score maps (higher diffusivity correlated with higher microglial activation) in MCI amyloid negative subjects in the temporal lobe (coordinates: 28 ‐3 ‐32, corrected p<0.001, k=7363). In MCI amyloid positive subjects, we found positive correlation in the parietal lobe (coordinates: ‐47 ‐41 39, corrected p=0.008, k=5712).ConclusionWe found colocalized diffusivity and microglial changes in the early stage of the disease, in the temporal lobe of MCI amyloid negative participants and in later stages of the disease, in the parietal lobe of MCI amyloid positive participants. These results suggest the potential of DTI diffusivity and microglial activation imaging in detecting early neuronal damage occurring in dementia.