Blood Pressure and Memory Novel Approaches to Modeling Nonlinear Effects in Longitudinal Studies

Background: Linear models cannot capture nonlinear associations when the relationships between cognition and risk factors vary across risk levels. We demonstrate a method of modelling nonlinear associations using the example of blood pressure (BP) and memory. Methods: We measured memory and BP (in mm Hg) annually for 10 years in a population-based cohort (N=1982) aged 65+. We evaluated the relationship between BP and memory at the same time points using both linear mixed models and generalized additive mixed models with smoothing splines, adjusting for relevant covariates. Results: Linear mixed models found no significant associations. Generalized additive mixed models detected different associations between BP and memory across baseline BP categories (normotensive, hypertensive, hypotensive). Among normotensives, systolic blood pressure (SBP)/diastolic blood pressure (DBP) around 140/80 was associated with the highest, while SBP/DBP around 110/60 was associated with the lowest, predicted memory scores. Among hypertensives, SBP/DBP around 130/85 was associated with the highest, while SBP/DBP around 150/65 was associated with the lowest, predicted memory scores. Among hypotensives, no significant association was found. Among both normotensives and hypertensives, a DBP >75 was associated with better memory. Conclusions: By modelling nonlinear associations, we showed that the relationship between BP and memory performance varied by baseline BP among normotensives and hypertensives.