Dynamic association between AT(N) profile and cognition mediated by cortical thickness in Alzheimer’s continuum

BACKGROUND: The recently-proposed National Institute on Aging and Alzheimer’s Association research framework organizes Alzheimer’s disease (AD) biomarkers based on amyloid/tau/neurodegeneration (AT(N)). This study investigated the mediating effect of structural change in brain MRI on changes in cognitive function according to initial AT(N) profiles. METHODS: We included 576 subjects (cognitively unimpaired (N = 136), mild cognitive impairment (N = 294), dementia (N = 146)) from the Alzheimer’s disease Neuroimaging Initiative study. The parallel-process latent growth curve model was applied to test the mediational effect of cortical thickness growth trajectory between the initial AT(N) profiles and cognitive growth trajectory. RESULTS: In Alzheimer’s continuum, only the A + T + (N)+ profile showed a mediational effect of the cortical thickness growth trajectory. A + T − (N)− was not sufficient to induce direct or indirect effects on cognitive dysfunction, and A + T + (N)− showed a significant direct path from an altered cortical thickness to cognitive decline. CONCLUSION: The sequential effect between changes in brain MRI and cognition varied by baseline AT(N) profile, suggesting the dynamic changes in the relationships among biomarkers in the current cascade model.