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

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 <30; Normal: 30 to <50; Borderline: [&ge;]50; and High: [&ge;]60 mmHg), and tested for differences in memory decline across groups. Stratified analyses were similarly conducted across other blood pressure measures, racial, age and sex groups. Findings Non-linear associations indicated that memory decline was particularly noticeable for pulse pressure [&ge;]60 mmHg. Compared with normal pulse pressure, [&ge;]60 mmHg was associated with worse memory performance (pooled {beta} -0.062 SD; 95% CI -0.107 to -0.016) and greater memory decline with age (-0.026 SD/year; -0.036 to -0.015), including among normotensive individuals. Findings were consistent across diverse regional cohorts (UK, US and China), racial groups, age strata and sexes. Interpretation Pulse pressure over 60 mmHg is associated with elevated cognitive risk, independent of blood pressure measures, even among normotensive individuals. These findings support pulse pressure thresholds as clinically interpretable and complementary markers of cognitive risk.