Plasma p‐tau markers, vascular factors, and cognitive decline in the CIMA‐Q cohort

INTRODUCTION: We evaluated associations between phosphorylated au 217 (p-tau217), p-tau181, p-tau231, and vascular risk factors with cognitive outcomes across the Alzheimer's disease (AD) continuum. METHODS: Baseline plasma p-tau concentrations and vascular risk factors were assessed in 277 Consortium for the Early Identification of Alzheimer's Disease-Quebec (CIMA-Q) participants. Associations between these markers, cognition, and clinical progression over on average 3.10 years were examined. RESULTS: Higher plasma p-tau levels were associated with worse cognition at baseline and over time, with the strongest effect observed with p-tau217 in cognitively impaired individuals (β = -0.49, p < 0.001). Hypertension was further linked to steeper memory and executive function decline (β = -0.10, both p = 0.04) in this group, and it amplified the effect of p-tau217 on cognitive decline across the whole group. Higher p-tau217 levels were associated with cognitive decline in cognitively unimpaired individuals, and it also predicted progression from mild cognitive impairment (MCI) to AD dementia (hazard ratio [HR] = 1.22, p = 0.016). DISCUSSION: Plasma p-tau217 was the most sensitive marker of cognitive decline, with hypertension contributing to longitudinal cognitive changes.