Lower complexity and higher variability in beat-to-beat systolic blood pressure are associated with elevated long-term risk of dementia: The Rotterdam Study

Abstract

Introduction: We hypothesized that subclinical disruption in blood pressure (BP) dynamics, captured by lower complexity and higher variability, may contribute to dementia risk, above and beyond BP levels.

Methods: This prospective cohort study followed 1835 older adults from 1997 to 2016, with BP complexity quantified by sample entropy and BP variability quantified by coefficient of variation using beat-to-beat BP measured at baseline.

Results: Three hundred thirty-four participants developed dementia over 20 years. Reduced systolic BP (SBP) complexity was associated with a higher risk of dementia (hazard ratio [HR] comparing extreme quintiles: 1.55; 95% confidence interval [CI]: 1.09-2.20). Higher SBP variability was also associated with a higher risk of dementia (HR comparing extreme quintiles: 1.57; 95% CI: 1.11-2.22. These findings were observed after adjusting for age, sex, apolipoprotein E (APOE) genotype, mean SBP, and other confounding factors.

Discussions: Our findings suggest that lower complexity and higher variability of beat-to-beat SBP are potential novel risk factors or biomarkers for dementia.

Keywords: Alzheimer's disease; blood pressure; blood pressure complexity; blood pressure variability; dementia; prospective cohort.

Figure 1.. Illustration of beat-to-beat SBP measurements with the same mean but different levels of complexity and variability

Hypothetical Interpretation: Panel A visualizes the scenario of intact BP regulation, in which numerous and hormonal feedback mechanisms are making flexible adaptations sensitively, manifested as many small disturbances on the waveform, to minimize BP variability (high complexity and low variability). Panel B visualizes the scenario in which the complex interactions between multiple regulatory feedback loops are partially impaired, but BP variability can still be largely limited through compensatory mechanism (low complexity and low variability). Panel C visualizes the scenario in which the complex feature of BP regulation is further impaired and BP variability cannot be effectively buffered by compensatory mechanism (low complexity and high variability).

Figure 2.. Cumulative incidence of all-cause dementia across quintiles of SBP complexity (A) and variability (B)

*SBP = Systolic Bloood Pressure; Q1-Q5 represent 1^st~5^th quintiles of the corresponding measures; Q1 is the bottom quintile and Q5 is the top quintile.