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Evaluation of Longitudinal [18F]GTP1 Tau Burden Metrics in the Tauriel Phase II Study

2022; Wiley; Volume: 18; Issue: S6 Linguagem: Inglês

10.1002/alz.061266

1552-5279

Sandra Sanabria Bohórquez, Paul T. Manser, Suzanne L. Baker, Mira Blendstrup, Karen Pickthorn, Edmond Teng,

Advanced MRI Techniques and Applications

Abstract Background Conventional measures of tau PET longitudinal change focus on SUVR. However, a small (n=57) observational [ 18 F]GTP1 study including a broad range of Alzheimer’s disease (AD) participants suggested tau Extent and Load could measure disease progression over 12 months with greater precision than SUVR. We assess the performance of these metrics in a larger 73‐week study in prodromal‐to‐mild AD. Methods We analyzed 109 prodromal (pAD) and 180 mild (mAD) [ 18 F]GTP1 scans in the semorinemab Phase 2 Tauriel study (NCT03289143). Quantification was performed using the cerebellum as reference. In a given ROI, extent was defined as the fraction of voxels above a scan‐specific threshold (mean cerebellar gray SUVR plus 2 standard deviations). Load was defined as Extant multiplied by the product of the mean SUVR of above‐threshold voxels. Analyses included the whole cortical gray (WCG), temporal meta‐ROI (excluding Braak 1/2, TMP), and Braak ROIs. As no treatment effects were observed with semorinemab, data were pooled across treatment and placebo arms. Relationships between endpoints were assessed with Spearman correlations (ρs), and endpoints changes were compared using Cohen’s D effect size (ES). Results At baseline, a slightly higher correlation was observed between SUVR and Load (ρs=0.89‐0.97) than between SUVR and Extent (ρs=0.64‐0.91) partly due to the smaller dynamic range for Extent in high‐tau burden regions (Figure 1). Longitudinal changes were correlated and consistent across endpoints (Figure 2). Extent ES values were lower than SUVR and Load ES, which showed similar performance (Table 1). Prognostic associations with baseline WCG measures were similar in pAD and mAD for predominantly cognitive measures ADAS‐COG and RBANS. Weaker prognostic associations were observed for CDR‐SB and ADCS‐ADL incorporating functional status (Table 2). Conclusion Higher baseline tau burden was associated with faster clinical decline in pAD and mAD. There was not obvious advantage of using Extent or Load; [ 18 F]GTP1 SUVR is a robust measurement for assessing longitudinal change in multi‐site clinical trials settings. Figure 1. Relationship between tau burden metrics. Figure 2. Relationship between change in tau burden. Table 1. Cohen’s D ES±95%CI of imaging endpoints change over 73 weeks. Table 2. Prognostic associations of baseline WCG tau burden measurements with cognitive change measures.