Pulse pressure thresholds associated with cognitive impairment across diverse regional and ethnic populations

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Background As dementia prevalence rises globally, it is critical to find preventions that target modifiable risk factors like blood pressure. Pulse pressure (PP), a marker of arterial stiffness, contributes independently to cognitive impairment. Yet, clinically interpretable thresholds for PP for cognitive decline remain undefined. We examined the independent association between PP and domain-specific cognitive trajectories and identified PP thresholds associated with greater cognitive decline across ethnically diverse regional populations. Methods Data were harmonized across three longitudinal cohorts (54,878 participants with up to 20 years follow-ups and 266,144 observations). Linear mixed-effects models identified a nonlinear association between PP and cognition (memory, orientation, and executive function), whereby cognitive decline accelerated after around 50 mmHg of pulse pressure, despite controlling for mean arterial pressure and dementia risk factors. Stratification based on PP thresholds (Low: PP