Cumulative Blood Pressure as a Marker of Early Cognitive Decline

1.

Dementia represents one of the most pressing and rapidly escalating global health challenges of the 21st century. The number of individuals living with dementia is projected to increase from approximately 57 million in 2019 to more than 153 million worldwide by 2050 [1], largely driven by population aging and increased life expectancy. Beyond its profound impact on memory and cognition, dementia is strongly associated with progressive loss of independence in activities of daily living and substantial caregiver burden [2]. Moreover, individuals with cognitive impairment often exhibit higher rates of cardiovascular morbidity and mortality [3], underscoring the systemic nature of the disease. Consequently, the identification and modification of preventable risk factors for dementia have become urgent global priorities.

Hypertension is one of the most important and potentially modifiable risk factors for dementia [4]. It is highly prevalent among individuals with cognitive impairment and dementia [5], and mounting epidemiological evidence suggests that elevated blood pressure (BP)—particularly during midlife—substantially increases the risk of developing cognitive decline and dementia in later years [6, 7]. Chronic exposure to elevated BP may contribute to cerebral small vessel disease, white matter injury, impaired cerebral autoregulation, and neurodegenerative processes [8], thereby providing a possible biological explanation for this association. Despite this strong mechanistic and observational evidence, effective strategies specifically targeting the prevention of dementia through BP control remain insufficiently established. Therefore, a deeper understanding of how BP exposure across the life course contributes to cognitive decline is essential for developing more effective preventive strategies.

Hua et al. examined the association between cumulative BP exposure and cognitive decline using data from 7877 participants in the nationwide China Health and Retirement Longitudinal Study (CHAELS) (mean age 58.4 ± 9.0 years; 46.8% men) [9]. Cumulative BP was calculated as the mean BP from 2011 to 2013 multiplied by the time interval between visits. Over a median follow‐up of 6.9 years, higher cumulative systolic BP (SBP) and pulse pressure (PP)—but not diastolic BP (DBP)—were independently associated with accelerated cognitive decline. Each standard deviation increase in cumulative SBP and PP was significantly related to faster decline in global cognitive scores. Compared with the lowest quartile, participants in the highest quartile of cumulative SBP and PP experienced steeper annual cognitive decline, whereas cumulative DBP showed no significant association. The authors also observed dose—response relationships and subgroup differences by sex and age. These findings suggest that cumulative BP indicators may be useful in clinical practice for identifying individuals at high risk of cognitive impairment, highlighting the importance of long‐term BP burden in shaping cognitive trajectories and supporting sustained BP management across the life course as a potential strategy for preserving cognitive health.

An important strength of the present study lies in its evaluation of cumulative BP load in an Asian population. While numerous studies have reported that increased BP variability is associated with cognitive decline and dementia [10, 11, 12], cumulative BP exposure represents a complementary but distinct construct. Rather than capturing short‐term fluctuations, cumulative BP load reflects the integrated hemodynamic burden sustained over time, incorporating both BP level and duration of exposure. In this sense, it provides a time‐weighted measure of chronic hypertensive stress imposed on the cerebral vasculature.

Prolonged exposure to elevated BP is known to contribute to progressive target organ damage, including cerebral small vessel disease and microstructural brain injury [13, 14]. Because cognitive changes often precede overt cognitive impairment or dementia diagnosis by many years [15, 16], cumulative BP metrics may be particularly useful for detecting early cognitive trajectories before the development of clinically manifest disease. This time‐integrated approach may therefore offer greater sensitivity in identifying subclinical vascular contributions to cognitive decline compared with binary endpoints such as incident dementia.

The focus on an Asian cohort is especially relevant. Several epidemiological studies have suggested that hypertension may confer a stronger association with stroke and other brain‐related outcomes in Asian populations compared with Western populations [17, 18]. Differences in salt sensitivity [19], vascular structure [20], and potential genetic predispositions have been proposed as contributing factors [21]. Interestingly, this paper also found that cumulative DBP elevation was not associated with cognitive decline, differing from findings primarily from Western countries [22, 23]. While differences in participant ethnicity and age groups were cited as reasons, these variations in BP values may also hold the key to understanding differences in dementia incidence related to BP between Asian and Western populations. A recent review also suggested that the mechanism by which hypertension‐associated elevation of endothelial β‐site amyloid precursor protein cleaving enzyme 1 (BACE1) affects cerebral microvascular disease may differ between Western and Asian populations [24]. If prolonged hypertensive exposure exerts a greater impact on cerebral outcomes in Asian individuals, strict control of cumulative BP burden—particularly during midlife—may be crucial for reducing the risk of cognitive impairment, dementia, and cardiovascular events. Further investigation into the influence of ethnicity on the effects of BP on the brain is anticipated.

Future research should move toward an integrated hemodynamic framework that incorporates cumulative BP load, BP variability, and out‐of‐office BP measurements. These dimensions capture distinct but complementary aspects of vascular stress. BP variability reflects dynamic instability in vascular regulation [25], whereas cumulative BP load represents the time‐integrated burden of hypertension. However, most cumulative BP metrics to date have relied on office‐based measurements obtained at limited time points [14, 26, 27], potentially underestimating the true long‐term hemodynamic exposure experienced by the brain.

In this context, the combination of cumulative BP assessment with out‐of‐office BP monitoring—including ambulatory and home BP measurements—may substantially enhance risk stratification. Out‐of‐office BP provides critical information on nocturnal hypertension, nighttime BP dipping patterns [28], morning surge [29], and masked hypertension [30], all of which have been independently linked to target organ damage and adverse brain outcomes. By extending cumulative BP concepts to longitudinal out‐of‐office data, it may become possible to quantify “cumulative hemodynamic load” with greater physiological precision, capturing both duration and circadian patterns of BP exposure. Such an approach could allow earlier identification of individuals at risk for vascular‐related cognitive decline and may offer a more actionable biomarker for preventive intervention. In the era of digital health and remote monitoring, the routine accumulation of home BP data over months and years makes the operationalization of cumulative out‐of‐office BP load increasingly feasible. Ultimately, integrating cumulative exposure metrics with variability indices and out‐of‐office measurements may provide a more comprehensive representation of life‐course vascular burden and its impact on cognitive aging and cardiovascular disease outcomes.

Taken together, the findings of this study suggest that cumulative BP load may serve as a clinically meaningful marker of early vascular‐related brain injury in Asian populations and highlight the importance of minimizing long‐term hypertensive exposure to preserve both cognitive and cardiovascular health.

Funding

The authors have nothing to report.

Consent

The authors have nothing to report. This article is a commentary and does not involve human participants.

Conflicts of Interest

The authors declare no conflicts of interest.