Relationship of Atrophy and Tau Imaging Subtypes in Prodromal and Clinical AD

Abstract

AbstractBackgroundAmyloid‐positive MCI and AD participants show heterogeneity in patterns of atrophy and tau‐deposition. We sought to directly compare the previously‐defined subtypes (hippocampal sparing (HpSp), limbic predominate (LP), typical AD (tAD), and minimal atrophy) derived from [18F]flortaucipir PET (T) and structural MRI (N) in the context of positive amyloid (A). In addition, we examined assessed associations between demographic factors and subtype group for atrophy or tau.Methods243 amyloid‐positive participants from ADNI with MRI and tau PET scans at the same visit were included (160 MCI, 83 AD). Brain volumes were extracted using Freesurfer version 6 and tau PET SUVR values were extracted using standard techniques. Hippocampal to cortical ratios for grey matter volume and tau SUVR were calculated as previously described (Risacher et al. 2017 Neurology). Minimal pathology subjects showed similar levels of atrophy relative to cognitive normal participants. Relationships between atrophy‐ and tau‐based subtypes, as well as their relationship to sex and race/ethnicity were assessed using a Chi‐square test. An ANOVA model was used to compare age and education between atrophy‐ and tau‐based subtypes.ResultsA significant association between tau‐based and atrophy‐based subtypes was observed, driven by consistency in minimal atrophy, HpSp, and tAD groupsp = 0.024). In addition, differences by sex and race/ethnicity were also observed for atrophy but not tau subtypes with non‐Hispanic Whites most likely to be either minimal atrophy or tAD, while African Americans were more likely to be HpSp. Finally, significant differences in age and education were observed across the atrophy subtypes, with the HpSp group being younger and less educated, while the LP were older and more educated.ConclusionsOverall, we observed consistency between atrophy‐based and tau‐based subtypes, especially minimal pathology, tAD, and HpSp forms. Interesting associations between demographics and atrophy but not tau subtypes were also observed. Future studies in larger and more diverse samples are needed. These results underscore the importance of examining heterogeneity in amyloid‐positive MCI and AD across multiple modalities to better understand patterns of A/T/N pathophysiology that may have implications for risk of progression and personalized therapeutic strategies.