One-Year Longitudinal Changes in Tau Accumulation on [¹⁸F]PI-2620 PET in the Alzheimer Spectrum

Abstract

We investigated the longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients in the Alzheimer disease (AD) continuum using 2-(2-([¹⁸F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c′]dipyridine ([¹⁸F]PI-2620) PET. Methods: We prospectively enrolled 52 participants (age, 69.7 ± 8.4 y; 18 men and 34 women): 7 with normal cognition, 28 with mild cognitive impairment, and 17 with AD. They all completed the [¹⁸F]PI-2620 and [¹⁸F]florbetaben PET, MRI, and neuropsychologic tests at baseline and, excepting the [¹⁸F]florbetaben PET, at the 1-y follow-up. Amyloid-β (Aβ) PET images were visually scored as positive (+) or negative (−). Patients on the AD continuum, including Aβ+ mild cognitive impairment and AD, were classified into early-onset (EO+) (<65 y old) or late-onset (LO+) (≥65 y old) groups. [¹⁸F]PI-2620 PET SUV ratios (SUVRs) were determined by calculating the cerebral–to–inferior cerebellar ratio. Cortical volumes were calculated using 3-dimensional T1-weighted MRI. The correlation between tau accumulation progression and cognitive decline was also investigated. Results: The global [¹⁸F]PI-2620 PET SUVRs were 1.04 ± 0.07 in 15 Aβ− patients, 1.18 ± 0.21 in 20 LO+ patients (age, 76.7 ± 3.8 y), and 1.54 ± 0.38 in 17 EO+ patients (age, 63.4 ± 5.4 y; P < 0.001) at baseline. The global SUVR increased over 1 y by 0.05 ± 0.07 (3.90%) and 0.13 ± 0.22 (8.41%) in the LO+ and EO+ groups, respectively, whereas in the Aβ− groups, it remained unchanged. The EO+ group showed higher global and regional tau deposition than did the Aβ− and LO+ groups (P < 0.05 for each) and rapid accumulation in Braak stage V (0.15 ± 0.25; 9.10% ± 12.27%; P = 0.016 and 0.008), Braak stage VI (0.08 ± 0.12; 7.16% ± 10.06%; P < 0.006 and 0.005), and global SUVR (P = 0.013) compared with the Aβ− group. In the EO+ group, the changes in SUVR in Braak stages II–VI were strongly correlated with the baseline and changes in verbal memory (P < 0.03). The LO+ group showed higher tau accumulation in Braak stage I–IV areas than did the Aβ− group (P < 0.001 for each). In the LO+ group, the change in SUVR in Braak stages III and IV moderately correlated with the change in attention (P < 0.05), and the change in SUVR in Braak stages V and VI moderately correlated with the change in visuospatial function (P < 0.005). Conclusion: These findings suggest that [¹⁸F]PI-2620 PET can be a biomarker to provide regional and chronologic information about tau pathology in the AD continuum.