Background

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 were used to estimate nonlinear association between PP and cognition (memory, orientation, and executive function), while controlling for mean arterial pressure and dementia risk factors. Different PP threshold groups (Low: PP <30; Normal: 30 to <50; Borderline: ≥50; and High: ≥60 mmHg) associated with cognition were estimated. 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 ≥60 mmHg. Compared with normal pulse pressure, ≥60 mmHg was associated with worse memory performance (pooled β −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.