A multimodal clinical diagnostic approach using MRI and 18F-FDG-PET for antemortem diagnosis of TDP-43 in cases with low–intermediate Alzheimer’s disease neuropathologic changes and primary age-related tauopathy

To evaluate the utility of clinical assessment scales for MRI and 18F-FDG-PET as potential in vivo predictive diagnostic tools for TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy in cases with low–intermediate Alzheimer's disease neuropathologic changes (ADNC) and primary age-related tauopathy (PART). We conducted a cross-sectional analysis on patients with antemortem MRI and 18F-FDG-PET scans and postmortem diagnosis of low–intermediate ADNC or PART (Braak stage ≤ III; Thal β-amyloid phase 0–5). We employed visual imaging scales to grade structural changes on MRI and metabolic changes on 18F-FDG-PET and statistically compared demographic and clinicopathological characteristics between TDP-43 positive and negative cases. Independent regression analyses were performed to assess further influences of pathological characteristics on imaging outcomes. Within-reader repeatability and inter-reader reliability were calculated (CI = 0.95). Additional quantitative region-of-interest analyses of MRI gray matter volumes and PET ligand uptake were performed. Of the 64 cases in the study, 20 (31