Abstract Body: Introduction
Although vascular dysregulation is emerging as a contributor to the pathophysiology of Alzheimer’s disease and related disorders (ADRD), studies have focused on linear variability, which limits evaluating dynamics and regulation of temporal vascular signals.
Hypothesis
We hypothesize that ADRD is characterized by the loss of regulated biological functions, including decreased system complexity and function in blood pressure (BP). To test this, we quantified the degree of nonlinear vascular dysregulation using 24-h BP time-series data and evaluated their association with cognitive impairment and dementia.
Methods
We analyzed 1,602 participants from the Maracaibo Aging Study as the discovery cohort and 657 participants from SPRINT as the replication cohort (68 individuals had AD-plasma biomarkers). 24-h BP measures were arranged in time-series and missing values were imputed using multiple imputation by chained equations. Metrics of nonlinear dynamics included entropy, detrended fluctuation analysis (DFA), and Poincaré analysis (including the short-term variability [SD1] / long-term variability [SD2] ratio and Poincaré area). Outcomes included global cognition, mild cognitive impairment (MCI), and baseline and incident dementia. Regression models were adjusted by age, sex, conventional risk factors, and the mean 24-h BP level.
Results
The mean age was 64.7±9.3y in the discovery cohort (68.5% were women) and 69.4±9.4y in the replication cohort (28.4% were women). High entropy and Poincaré with low DFA suggest unstable and disorganized BP regulation, while low entropy and Poincaré with high DFA reflect a more rigid and predictable dynamic system (Figure 1: Panels A&D vs. C&F). In the discovery cohort, a greater SD1/SD2 and Poincaré area were associated with lower cognitive function (β were -0.051 and -0.047; respectively, P≤0.020) and higher odds ratios (OR) of having MCI (ORs ranged from 1.34 to 1.38; P≤0.001). Greater entropy and Poincaré were associated with dementia prevalence (ORs ranged from 1.36 to 1.51) and incidence (HRs ranged from 2.41 to 6.27) in both cohorts. A higher entropy was associated with greater levels of pTau-217 (β, 0.276).
Conclusions
More chaotic and unstable 24-h BP dynamics are associated with cognitive impairment and dementia risk. Given that emerging technologies capture biological signals over extended periods, nonlinear analysis of vascular signals may provide valuable insights into the vascular pathogenesis of ADRD.