Trajectory of MRI and FDG‐PET biomarkers in Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) has a long preclinical phase, which is hypothesised to start with the accumulation of ß‐amyloid (Aß) plaques, followed by tau neurofibrillary tangles and neurodegeneration. Despite presenting quite different types of information, MRI‐derived volumetric measures and FDG‐PET‐derived metabolism are both commonly used as proxy of neurodegeneration in AD. The aim of this work is to assess the trajectory of both of these biomarkers in AD, relative to time to amyloid‐positivity.Method3289 MRI scans (682 participants) and 2472 FDG‐PET scans (1296 participants) were included from the ADNIGO, 1,2 and 3 cohorts. For MRI scans, total volume was calculated for a meta‐ROI consisting of entorhinal, inferior, middle temporal and fusiform gyri. For FDG‐PET, standardized uptake value ratios (SUVR) were calculated from 30‐60 min post injection for a meta‐ROI consisting of the angular, posterior cingulate and inferior temporal gyri, normalised to the pons. All metrices were transformed into z‐scores using the references values of the Aß‐negative subjects. Age of amyloid‐positivity was determined by fitting a nonlinear mixed effects model to 3607 Centloid values corresponding to 1690 participants. Next, time to amyloid‐positivity was calculated for each scan. The relationship between time to amyloid‐positivity and (z‐scored) SUVR or cortical volume values was modelled using a non‐linear mixed effects model with spline function and trajectories from both modalities were compared.ResultBaseline demographics can be found in Table 1. Figure 1 shows the trajectory of amyloid deposition that was used to determine age of amyloid‐positivity. Cortical volume and SUVR showed similar trajectories over time, with steeper decline in both measures after the event of amyloid‐positivity (Figure 2). The overlay of both biomarker trajectories shows that for the meta‐ROI, there is no difference in when these biomarkers become abnormal.ConclusionThe present results suggest that measures of neurodegeneration from MRI and FDG‐PET scans corresponding to a meta‐ROI, follow very similar trajectories. Future work will investigate if this also holds true for smaller regions of interest.