Association of tau accumulation and atrophy in mild cognitive impairment: a longitudinal study

Objective To examine the patterns of longitudinal tau accumulation and cortical atrophy and their association in subjects with mild cognitive impairment (MCI). Methods We collected 23 participants (60-89 years old, 11 males/12 females) with MCI from the Alzheimer's Disease Neuroimaging Initiative database. All participants underwent(18)F flortaucipir (FTP) positron emission tomography (PET) and structural magnetic resonance imaging (MRI) scans at the baseline and follow-up visits (12-36 months). General linear models with covariates (baseline age, sex) were used to detect brain areas of significant tau accumulation and atrophy over time. Mediation analysis was employed to explore the potential reason for sequential biomarker changes in MCI progression, adjusting for baseline age, sex, and education level. Results Voxel-wise tau accumulation in MCI subjects was predominantly located in the inferior temporal cortex, middle temporal cortex, parietal cortex, posterior cingulate, precuneus, and temporoparietal regions (P < 0.001), and MRI atrophy included the inferior-middle temporal lobe, parietal lobe, and precuneus (P < 0.001). Longitudinal FTP accumulation was moderately associated with annualized MRI cortical atrophy (r = 0.409, 95% CI: 0.405-0.414,P < 0.01). Regional analyses indicated significant bivariate associations between annualized MRI cortical atrophy and FTP accumulation (baseline FTP cortical uptake and longitudinal FTP change). The results of the mediation analysis showed that the relationship between baseline FTP uptake and longitudinal cortical atrophy was partly mediated by the longitudinal FTP cortical change (indirect effect: 0.0107,P = 0.04). Conclusions Our findings provide a preliminary description of the patterns of longitudinal FTP accumulation and annualized cortical atrophy in MCI progression, and MCI subjects with high tau binding levels show an increase risk of longitudinal tau accumulation, atrophy, and cognitive decline. Trial registrationNCT00106899. Registered 1 April 2005,