One year longitudinal change of tau accumulation on [18F]PI‐2620 PET in Alzheimer spectrum

Abstract

AbstractBackgroundWe investigated longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients with Alzheimer’s disease (AD) spectrum using [18F]PI‐2620 PET.MethodWe enrolled 54 (69.9±8.5 y, M:F = 16:38) participants (8 cognitively normal [NC], 28 mild cognitive impairment [MCI], 18 AD) who completed [18F]PI‐2620 PET scans at baseline and 1 y follow up. Subject also underwent [18F]florbetaben PET (baseline only), MRI and neuropsychological tests. Aβ PET images were visually scored as positive or negative. Aβ+ MCI & AD were classified into early onset (<65 y, EO+) and late onset (≥65, LO+) group. Standardized uptake value ratios (SUVr) of [18F]PI‐2620 PET were determined by cerebral to inferior cerebellar ratio and corrected for partial volume effect. Cortical volumes were calculated from 3D T1‐weighted MR images. We also investigated a correlation between the progression of tau accumulation and cognitive decline.ResultThirty eight out of 57 participants showed Aβ+ (1 NC, 20 MCI, 17 AD). Global SUVr values of [18F]PI‐2620 PET were 0.96±0.07 in 7 Aβ‐ NC, 1.23±0.41 in 17 LO+ (76.7±3.8y) and 1.86±0.87 in 20 EO+ (63.4±5.4y) (p<0.001). It increased by 0.09±0.14 (7.0%) in LO+ and 0.14±0.27 (11.6%) in EO+ in contrast to no change in NC‐. EO+ showed abundant tau accumulation in Braak III‐V areas at baseline with rapid accumulation in Braak V area (0.33±0.41 [13.9%] vs. 0.08±0.14 [6.7%], p = 0.010) than LO+ group. It showed abundant and rapid accumulation on Braak 3 areas in LO+ group (1.61±0.53 at baseline, change: 0.15±0.25 [8.2%]). Deterioration of the visuospatial function and verbal memory was associated with the progression of tau accumulation in Braak III‐V areas in EO+ group. Progressive atrophy in Braak III‐V areas were associated with the progression of tau accumulation in LO+ group whereas hippocampal atrophy did in EO+ group.ConclusionTau accumulation measured by [18F]PI‐2620 in EO+ showed rapid accumulation in Braak III‐V areas and correlated with deterioration of the visuospatial function and verbal memory. It suggests that [18F]PI‐2620 PET is potential biomarker for selecting therapeutic target and monitoring treatment effect for tau targeting treatment.