Abstract
BackgroundVariation 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 findingsIn 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.ConclusionsResults 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.
Highlights
Dementia is the most common neurodegenerative disease in elderly people, associated with high disability and dependency [1]
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
It has been reported that a larger variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) over time is associated with a higher risk of dementia during a follow-up of up to 8 years [9]
Summary
Dementia is the most common neurodegenerative disease in elderly people, associated with high disability and dependency [1]. Hypertension is a important risk factor, but its relation to dementia becomes complex with aging [4,5] This association may depend on time until diagnosis [6], and dynamic effects of blood pressure fluctuation are unlikely to be captured in a single measurement. Given the insidious onset of dementia, pathological processes of dementia affecting blood pressure may occur many years before the diagnosis, and short-term associations may be susceptible to reverse causation [10]. It is unknown whether blood pressure variation is associated with dementia in the long-term and whether the putative association changes over time. 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
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