Image‐based primary age‐related tauopathy as a risk of dementia: a five‐year longitudinal study

Abstract

AbstractBackgroundTo investigate cognitive and pathological (amyloid and tau) changes of image‐based primary age‐related tauopathy (PART) in a long‐term follow‐up cohort study.MethodIn this study, a total of 108 patients who were both negative in amyloid and tau PET images were enrolled. All participants completed the same two PET scans (18F‐flortaucipir for tau and 18F‐florbetaben for Aβ), and neuropsychological tests at least twice over 5 years. We defined PART+ as those who had a higher standardized uptake value ratio (SUVR) in the entorhinal cortex than the cutoff calculated by the Youden index. We investigated the cognitive and 18F‐florbetaben and 18F‐flortaucipir SUVR changes longitudinally between PART+ and PART‐ participants while adjusting for age, sex, education, and ApoE4.ResultCompared with PART‐, PART+ participants had more rapid worsening of MMSE (β=‐0.274, p<0.001), CDR‐SB (β=0.081, p<0.001), and memory function (β=‐0.140, p=0.008). No significant differences were observed in the language, visuospatial, frontal‐executive, attention domains, and total cognitive battery score. In PART+ participants, the annual Aβ accumulation rate from whole cortical SUVR was also increased (β=0.016, p=0.003), and a more rapid accumulation rate was observed in Alzheimer’s disease (AD) specific hot meta‐region‐of‐interest (meta‐ROI) SUVR, compared with PART‐ participants (β=0.019, p=0.001). The annual tau accumulation rate of PART+ was higher than PART‐ in the entorhinal cortex (β=0.010, p<0.001), however, no differences were observed in whole cortical SUVR tau.ConclusionThe PART+ participants showed a rapid cognitive decline in memory function as well as MMSE, and CDR‐SB, than those of PART‐. In addition, amyloid was accumulated at a faster rate in PART+ participants and tau was accumulated more rapidly in the medial temporal area. In conclusion, our longitudinal study suggests that image‐based entorhinal tau defined as a PART+ could be an earlier stage than the preclinical stage of AD.