Tau and amyloid show distinct relationships with cognitive decline in Alzheimer's disease: A multimodal PET-MRI study
Chileka Chiyanika, Nga Yan Chan, Wanting Liu, Lisa WC Au, Weitian Chen, Chunlei Liu, Sirong Chen, Eric YL Leung, Chi L Ho, Yuan Cai, Ho Ko, Qianyun Chen, Winnie CW Chu, Vincent CT Mok, Jill AbrigoBackground
Amyloid-β (Aβ) and tau show distinct relationships with brain injury in Alzheimer's disease. We evaluated if tau-associated MRI abnormalities persist after accounting Aβ and compared multimodal MRI with PET for classifying cognitive impairment. Multi-parametric MRI provides an accessible framework to capture complementary macrostructural, microstructural, and biophysical tissue alterations across the disease continuum.
Objective
To determine whether continuous global cortical tau burden independently relates to regional multi-parametric MRI metrics after controlling for Aβ, and to evaluate how effectively quantitative MRI versus PET markers reflect cognitive status and impairment.
Methods
Forty-four participants underwent amyloid/tau PET and advanced MRI (T1 volumetry, DTI, QSM, T1ρ). Covariate-adjusted multivariable linear regressions examined associations of global amyloid and tau burden with regional MRI measures. Mediation and ROC analyses were exploratory.
Results
After adjustment for Aβ, higher tau was nominally associated with lower amygdala and putamen fractional anisotropy, but no association survived FDR correction. Conversely, higher Aβ was associated with smaller hippocampal and amygdala volumes and higher hippocampal mean diffusivity, which partly mediated poorer MoCA and HKLLT performance. Hippocampal volume (AUC = 0.949) and mean diffusivity (AUC = 0.928) outperformed tau PET (AUC = 0.733) for classifying cognitive impairment.
Conclusions
All cognitively impaired participants were tau-positive, but continuous tau burden showed no clear association with cognition. Hippocampal MRI markers better reflected clinical status.