Plasma p-tau markers and vascular factors are associated with cognitive decline and clinical progression in the CIMA-Q cohort

Introduction: We compared associations between phosphorylated tau biomarkers (p-tau217, p-tau181, p-tau231) and vascular risk factors with clinical progression and cognitive decline along the AD continuum. Methods: Baseline plasma p-tau concentrations and vascular risk factors were assessed in 280 CIMA-Q participants. Associations between these markers, cognition and clinical progression over 8 years were examined. Results: Elevated p-tau217 predicted progression from mild cognitive impairment (MCI) to AD dementia (p<.01), while hypertension predicted progression from cognitively unimpaired (CU) to MCI (p<.02). Higher p-tau levels, particularly p-tau217, and hypertension were linked to cognitive decline in MCI individuals. In the CU group, few associations were seen between p-tau levels and cognitive decline, with minimal effect of vascular risk factors. Discussion: Plasma p-tau217 was the most sensitive marker of AD-related decline, but hypertension was particularly relevant at earlier stages. The results highlight the need for multimodal profiling to optimize prediction and intervention along the AD continuum.