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

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-([F-18]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c ']dipyridine ([F-18]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 [F-18]PI-2620 and [F-18]florbetaben PET, MRI, and neuropsychologic tests at baseline and, excepting the [F-18]florbetaben PET, at the 1-y follow-up. Amyloid-beta (A beta) PET images were visually scored as positive (+) or negative (-). Patients on the AD continuum, including A beta+ mild cognitive impairment and AD, were classified into early-onset (EO+) (<65 y old) or late-onset (LO+) (>= 65 y old) groups. [F-18]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 [F-18]PI-2620 PET SUVRs were 1.04 +/- 0.07 in 15 A beta- 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 A beta- groups, it remained unchanged. The EO+ group showed higher global and regional tau deposition than did the A beta- 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 A beta- 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 A beta- 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 [F-18]PI-2620 PET can be a biomarker to provide regional and chronologic information about tau pathology in the AD continuum.