Towards clinical application of tau PET: Prognostics

Abstract

AbstractBackgroundTau PET is now considered to be a disease stage biomarker for reflecting of Alzheimer’s disease (AD) severity. Recent longitudinal studies showed a progression of cortical tau burden and a predictability of baseline tau PET for further tau accumulation, cortical atrophy, and even clinical progression in the short term. In this study, we sought to investigate long‐term changes in tau burden and predictability of tau PET for long‐term disease progression.MethodIn a cohort with 273 participants who had completed visit 1 (V1) assessments including two PET scans (18F‐florbetaben and 18F‐flortaucipir), MR imaging studies and neuropsychological function tests, 77 Aβ+ participants [9 cognitively unimpaired (CU) and 38 mild cognitive impairment (MCI), and 30 AD dementia (DEM)] completed visit 2 (V2) assessments at two years, and subsequently 39 Aβ+ participants (6 CU, 24 MCI, and 9 DEM) completed visit 3 (V3) assessments at about four years (mean 4.6 years) after the V1 study. After correcting for partial volume effect, we measured regional standardized uptake value ratio (SUVR) values with cerebellar crus median as a reference and regional volumes, as well.ResultDuring the short‐ (V1 to V2) and long‐term (V1 to V3) periods, tau burden significantly increased in the widespread cortex, particularly in the medial and lateral temporal cortices. In 33 cognitively impaired patients who completed both V2 and V3 scans, DEM patients exhibited higher global cortical tau accumulation rates (V1 to V2 = 0.066 and V2 to V3 = 0.058 SUVR/year) than MCI patients (V1 to V2 = 0.044 and V2 to V3 = 0.051 SUVR/year). Tau burden at V1 correlated strongly with the tau accumulation and volume reduction rates, particularly in the lateral temporal cortex and also correlated with the global cognitive decline rate, particularly in the prefrontal and parietal cortices. Likewise, in both short‐ and long‐term data, tau accumulation rate correlated with the volume reduction and global cognitive decline rates.ConclusionTau accumulated progressively throughout a four year long‐term follow‐up period. Progression of tau pathology, cortical atrophy and cognitive decline can be predicted by baseline tau burden. Tau PET is a useful imaging biomarker in predicting long‐term disease progression.