Rates of clinical progression according to biological Alzheimer's disease stages

Predicting the rate of cognitive decline and the likelihood of progression to dementia remains a critical unmet need in clinical settings. We assessed progression to mild cognitive impairment (MCI) and all-cause dementia in 492 individuals from the TRIAD, ADNI, and HABS-HD cohorts followed for an average of 2.49 years. Amyloid-positive participants were staged according to the Alzheimer's Association biological staging framework (A+T2-/A+T2MTL+/A+T2MOD+/A+T2HIGH+). Cognitively unimpaired (CU) individuals in the A+T2MTL+, A+T2MOD+, and A+T2HIGH+ biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to non-AD CU individuals. In individuals with MCI, advanced tau stage was associated with an 83% likelihood of developing dementia over 4 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression compared to amyloid-PET (positron emission tomography) status, tau-PET status, and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than non-AD controls, with the A+T2HIGH+ stage showing the steepest rate of decline (p < 0.001). Our results highlight the prognostic value of biological AD staging. Cognitively unimpaired (CU) individuals in all tau-PET (positron emission tomography)-positive biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to individuals without AD. In individuals with mild cognitive impairment (MCI), only the A+T2HIGH+ stage reached a point where 50% of individuals had progressed to all-cause dementia, after 2.36 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression to dementia compared to other PET biomarkers and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than individuals without AD, with the A+T2HIGH+ stage showing the steepest rate of decline.