Plasma p-tau217 was the most sensitive marker of cognitive decline across the Alzheimer's disease continuum, with hypertension contributing to longitudinal cognitive changes and amplifying the effect of p-tau217 on cognitive decline.
Key Findings
Results
Higher plasma p-tau217 levels were associated with worse cognition at baseline and over time, with the strongest effect observed in cognitively impaired individuals.
The strongest effect of p-tau217 on cognition was observed in cognitively impaired individuals (β = -0.49, p < 0.001)
Study included 277 CIMA-Q participants with baseline plasma p-tau concentrations assessed
Associations were examined over an average follow-up of 3.10 years
P-tau217 showed stronger associations with cognitive outcomes compared to p-tau181 and p-tau231
Results
Hypertension was linked to steeper memory and executive function decline in cognitively impaired individuals.
Hypertension was associated with steeper memory decline (β = -0.10, p = 0.04) in cognitively impaired individuals
Hypertension was also associated with steeper executive function decline (β = -0.10, p = 0.04) in the same group
Hypertension amplified the effect of p-tau217 on cognitive decline across the whole group
Results
Higher p-tau217 levels predicted progression from mild cognitive impairment (MCI) to AD dementia.
P-tau217 predicted progression from MCI to AD dementia with a hazard ratio of 1.22 (p = 0.016)
This finding indicates a 22% increased risk of progression to AD dementia per unit increase in p-tau217
P-tau217 also showed associations with cognitive decline in cognitively unimpaired individuals
Results
Plasma p-tau217 was identified as the most sensitive marker of cognitive decline among the three p-tau markers evaluated.
Three plasma p-tau markers were evaluated: p-tau217, p-tau181, and p-tau231
P-tau217 demonstrated superior associations with cognitive outcomes compared to the other two markers
The marker showed sensitivity to cognitive decline across the AD continuum, including in cognitively unimpaired individuals
Associations were assessed both cross-sectionally at baseline and longitudinally over approximately 3.10 years
Methods
The study evaluated associations between three plasma phosphorylated tau markers and vascular risk factors with cognitive outcomes in 277 participants across the AD continuum.
Study population consisted of 277 Consortium for the Early Identification of Alzheimer's Disease-Quebec (CIMA-Q) participants
Baseline plasma p-tau concentrations (p-tau217, p-tau181, p-tau231) and vascular risk factors were assessed
Mean follow-up duration was approximately 3.10 years
Participants spanned the AD continuum including cognitively unimpaired individuals and those with MCI
What This Means
This research examined blood-based biomarkers for Alzheimer's disease and cardiovascular risk factors to see how well they predict memory and thinking decline over time. The study followed 277 older adults from Quebec, Canada for an average of about three years, measuring three different forms of a protein called phosphorylated tau (p-tau) in their blood alongside vascular risk factors like high blood pressure. Among the biomarkers tested, p-tau217 stood out as the most sensitive indicator of cognitive decline, showing strong associations both in people who already had cognitive impairment and, importantly, even in those who appeared cognitively normal at the start of the study.
The research also found that high blood pressure (hypertension) independently contributed to faster decline in both memory and executive functioning in people who already had cognitive impairment. Furthermore, hypertension appeared to worsen the effect of elevated p-tau217 on cognitive decline across all participants. People with mild cognitive impairment (MCI) who had higher p-tau217 levels had a 22% increased risk of progressing to full Alzheimer's dementia for each unit increase in this marker.
This research suggests that combining blood-based tau biomarkers — particularly p-tau217 — with vascular risk factor assessment could improve early identification of individuals at risk for Alzheimer's disease progression. The finding that hypertension amplifies the negative effects of Alzheimer's-related protein buildup highlights the potential importance of managing cardiovascular health as part of strategies to address cognitive decline, though further research is needed to determine whether treating hypertension can modify Alzheimer's disease trajectories.
Cottez R, Peyrot C, Denis H, Tremblay C, Loiselle A, Dallaire-Théroux C, et al.. (2026). Plasma p-tau markers, vascular factors, and cognitive decline in the CIMA-Q cohort.. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71588