Summary: Patients who experience substantial changes in blood pressure over time have an increased risk of developing dementia.
In a new research study published in the open access journal PLOS Medicine, Albert Hofman and colleagues at Erasmus MC University Medical Center, Rotterdam, the Netherlands and Harvard T.H. Chan School of Public Health, Boston, United States report that people who experienced substantial changes in blood pressure over the long term were at greater risk of dementia than those who did not.
The authors studied 5,273 people in Rotterdam, the Netherlands at a mean age of 67.6 years, who were free of dementia at the beginning of the study and were followed-up for 14.6 years. After adjustment for age, sex and other factors that could affect the findings, at 15 years people in the highest quintile, who exhibited an increase in systolic blood pressure, had a hazard ratio of 3.31 (95% Confidence Interval 2.11-5.18) for risk of dementia as compared with those in the quintile with the least change in blood pressure. Those in the lowest quintile, with the largest fall in systolic blood pressure, had a hazard ratio of 2.20 (95% CI 1.33-3.63) for dementia risk, again compared to those with the least change. Variations in both systolic and diastolic blood pressure led to similar findings.
Assuming that Hofman and colleagues’ findings reflect a causal relationship between blood pressure variation and dementia, the authors note a “potential to prevent dementia through targeting blood pressure variability above and beyond the mere control of conventional blood pressure limits”, and note that the association observed over a long time period implies that interventions should be implemented earlier in life to yield potential benefits.
Funding: The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII), and the Municipality of Rotterdam. This work was partially supported by an unrestricted grant from the Janssen Prevention Center. YM was sponsored by the Rose Travelling Fellowship. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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Background Variation in blood pressure may relate to dementia risk via autonomic disturbance or hemodynamic mechanisms, but the long-term associations are unclear. We aimed to determine whether blood pressure variation over a period of years, considering both magnitude and direction, is associated with the risk of dementia.
Methods and findings In a prospective cohort study ongoing since 1989 in the Netherlands, 5,273 dementia-free participants (58.1% women; mean [SD] age, 67.6 [8.0] years) were included. As of 2016, 1,059 dementia cases occurred during a median follow-up of 14.6 years. Absolute variation in systolic blood pressure (SBP) was assessed as the absolute difference in SBP divided by the mean over two sequential visits every 4.2 (median) years, with the first quantile set as the reference level. The direction was the rise or fall in SBP, with the third quantile set as the reference level. We estimated the risk of dementia in relation to SBP variation measured at different time windows (i.e., at least 0, 5, 10, and 15 years) prior to dementia diagnosis, with adjustments for age, sex, education, apolipoprotein E (APOE) genotype, vascular risk factors, and history of cardiovascular disease. We repeated the above analysis for variation in diastolic blood pressure (DBP).
A large SBP variation was associated with an increased dementia risk, which became more pronounced with longer intervals between the assessment of SBP variation and the diagnosis of dementia. The hazard ratio (HR) associated with large variation (the highest quintile) increased from 1.08 (95% confidence interval [CI] 0.88–1.34, P = 0.337) for risk within 5 years of SBP variation measurement to 3.13 (95% CI 2.05–4.77; P < 0.001) for risk after at least 15 years since the measurement of SBP variation. The increased long-term risk was associated with both large rises (HR for the highest quintile, 3.31 [95% CI 2.11–5.18], P < 0.001) and large falls in SBP (HR for the lowest quintile, 2.20 [95% CI 1.33–3.63], P = 0.002), whereas the higher short-term risk was only associated with large falls in SBP (HR, 1.21 [95% CI 1.00–1.48], P = 0.017). Similar findings were observed for variation in DBP. Despite our assessment of major confounders, potential residual confounding is possible, and the findings on blood pressure variability over periods of years may not be generalizable to variability over periods of days and other shorter periods.
Conclusions Results of this study showed that a large blood pressure variation over a period of years was associated with an increased long-term risk of dementia. The association between blood pressure variation and dementia appears most pronounced when this variation occurred long before the diagnosis. An elevated long-term risk of dementia was observed with both a large rise and fall in blood pressure.