BackgroundAs 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.
MethodsData 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: [≥]50; and High: [≥]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.
FindingsNon-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 {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.
InterpretationPulse 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.
FundingAlzheimers Society, NIHR Cambridge Biomedical Research Centre, NIHR BioResource, Wellcome Trust, Medical Research Council, Addenbrookes Charitable Trust, Natural Science Foundation of China
Evidence before this studyBlood pressure is recognized as a key modifiable target for dementia. However, previous findings indicate that systolic blood pressure alone may not fully capture vascular aging contributions to cognitive decline. Pulse pressure - the difference between systolic and diastolic blood pressure - provides insights into the pulsatile component beyond conventional indices. Prior studies have reported associations between pulse pressure and cognitive impairment across individuals, but few have examined domain-specific impairment (e.g., memory) across diverse ethnoregional populations over extended periods of ageing within individuals. Evidence from arterial stiffness and pulsatile biology suggests that cognitive risk may increase non-linearly, accelerating only beyond specific blood pressure levels. Defining target thresholds is crucial for guiding public health and clinical interventions, yet to date, no clinically interpretable pulse pressure threshold has been established.
Added value of this studyWe demonstrate for the first time that clinically interpretable pulse pressure thresholds predict cognitive impairment independent of traditional blood pressure measures. By harmonizing three ethnically diverse regional populations (United Kingdom, United States and China), this study confirmed an overall association between higher pulse pressure and poorer cognitive function. We further showed that this association is non-linear, was most evident in memory function, and was independent of traditional blood pressure measures and established modifiable dementia risk factors. Pulse pressure [≥]60 mmHg was associated with worse memory performance and greater memory decline, including among normotensive individuals, with consistent findings across observed across multiple cohorts, racial groups (White, Black and Asian), age strata (mid-life and late-life) and both sexes. Furthermore, participants with pulse pressure [≥]50 mmHg had greater memory decline even among normotensive individuals.
Implications of all the available evidenceOur findings support the use of pulse pressure thresholds above 60 mmHg as a clinically interpretable and complementary marker to systolic blood pressure for assessing dementia risk across diverse populations, even among normotensive individuals. Timely monitoring pulse pressure above 50 mmHg may facilitate early identification of individuals at risk for cognitive decline.
0 Comments
Log in to join the discussion.