Age-frailty status jointly modifies the nonlinear association between systolic blood pressure and annual cognitive...

BackgroundCognitive impairment (including Alzheimer's disease), frailty, and hypertension are interlinked challenges in older adults. Among non-frail adults, prefrail older adults represent a crucial window for prevention. However, whether systolic blood pressure (SBP) affects cognitive decline differently across age-frailty strata, or what constitutes an optimal age-frailty-stratified target, remains unclear.ObjectiveTo investigate the association of SBP with annual cognitive aging rate in non-frail adults (robust/prefrail, ≥45years), focusing on nonlinearity and modification by age-frailty status, and to explore optimal SBP thresholds, especially in prefrail older adults.MethodsThis longitudinal analysis included 4723 non-frail adults from China Health and Retirement Longitudinal Study (2011-2018). SBP and annual cognitive aging rate (Z-score) were measured, with age and frailty categorized as middle-aged (45-64 years)/older (≥65 years), robust/prefrail. Linear regression and restricted cubic splines assessed associations, with interaction effect tested. Exploratory threshold and piecewise linear regression identified optimal SBP ranges and breakpoints.ResultsBesides linearity, a significant inverted U-shaped relationship existed between SBP and annual global cognition aging rate (p-nonlinear=0.049), with a peak at 120.1 mmHg overall, jointly modified by age-frailty status. A steep, distinct curve with a higher peak (130.8 mmHg; p-nonlinear=0.005) was found in prefrail older adults. The SBP-by-age-frailty nonlinear interaction was significant (p = 0.010) and improved model fit (p = 0.001). Divergent coefficients across breakpoints corroborated the robustness of the nonlinear SBP-cognition association in both populations. Episodic memory analyses showed highly concordant patterns above.ConclusionsTo optimize cognitive aging prevention, personalized SBP targets should be set based on age-frailty status, with relaxed thresholds for vulnerable prefrail older adults.