Understanding the Clinical Meaning of Cumulative Blood Pressure Exposure in Cognitive Outcomes

Dear Editor, We read with interest the nationwide population-based cohort study by Hua et al. investigating the association between cumulative blood pressure exposure and subsequent cognitive decline among middle-aged and older adults using data from the China Health and Retirement Longitudinal Study 1. The authors reported that higher cumulative systolic blood pressure and pulse pressure, but not diastolic blood pressure, were independently associated with accelerated cognitive decline. These findings contribute important longitudinal evidence supporting the relevance of long-term blood pressure exposure in cognitive aging research. One methodological aspect that deserves further clarification concerns the operational definition of cumulative blood pressure exposure. In the study, cumulative exposure was calculated using measurements obtained during two visits between 2011 and 2013 and multiplied by the interval between visits. Although this approach has been used previously, it may reflect short-term exposure rather than true long-term vascular burden across the life course. Prior longitudinal analyses suggest that cumulative blood pressure trajectories over extended periods provide more robust estimates of cerebrovascular injury risk and cognitive decline than limited exposure windows derived from only two measurement time points 2. Another point relates to the interpretation of the differential associations observed between systolic blood pressure, pulse pressure, and diastolic blood pressure. The absence of a significant association between cumulative diastolic blood pressure and cognitive decline contrasts with several cohort studies reporting domain-specific or age-dependent effects of diastolic pressure on cognitive trajectories. These discrepancies highlight the complexity of age-related hemodynamic changes and suggest that vascular stiffness and pulsatile load may partly explain the stronger relationship observed with pulse pressure compared with diastolic pressure alone 3. Residual confounding associated with antihypertensive treatment exposure also warrants consideration. Although medication use was included as a covariate, treatment intensity, duration, and longitudinal blood pressure variability were not incorporated into the cumulative exposure model. Previous meta-analyses have demonstrated that long-term blood pressure reduction is associated with a lower risk of cognitive decline and dementia, indicating that treatment-related factors may substantially modify the association between cumulative blood pressure indices and cognitive outcomes 4. Finally, the study evaluated cognitive decline using composite z-score–based measures derived from multiple domains rather than incident dementia endpoints. While such measures are sensitive to early cognitive changes, their clinical interpretation in relation to long-term neurodegenerative risk remains uncertain. Large cohort studies have shown that cumulative vascular risk exposure across midlife is strongly associated with structural brain aging and later-life cognitive impairment, suggesting that integrating imaging-based or clinical endpoints could further strengthen interpretation of cumulative blood pressure effects on cognitive trajectories 5. Sincerely, All of the authors contributed planning, writing, and revision. This work did not receive any specific funding. The author declares no conflicts of interest. No new data was generated or analyzed in support of this letter to the editor.