BACKGROUND: Increased age is a primary risk factor for cardiovascular disease and cognitive decline. However, there is significant variation in rates of deteriorating health, and maintaining vascular function has emerged as a promising target for intervention. Relevant contributions from the peripheral vasculature to the maintenance of cognition remain understudied, especially at various levels (e.g., macro vs. microvascular). Therefore, our purpose was to determine the relative contributions of arterial stiffness, central pulse pressure (cPP), and reactive hyperemia to cognition. METHODS: 99 healthy adults (50 men, 49 women) across the lifespan (19-90 yrs) volunteered to complete a vascular occlusion test (VOT) and provide measures of arterial stiffness (as quantified by pulse wave velocity [PWV]), and cPP. A near-infrared spectroscopy (NIRS) device was attached to the forearm during the VOT (3 min baseline, 5 min occlusion, 3 min reperfusion). The highest skeletal tissue oxygenation (StO2, %) observed following occlusion was defined as StO2max (marker of reactive hyperemia). PWV was assessed by the time difference between carotid-femoral pulses. Cognition was defined as the time to complete Part A of the trail-making test. Pearson correlations were used to evaluate relationships between the vasculature and cognition. Regression analyses were used to determine the full-model and stepwise linear regression model. RESULTS: There were significant relationships between cognition and PWV (r=0.442;p=<.001), StO2max (r=-0.362;p=<.001), and cPP (r=0.328;p=<.001). Age had the greatest standardized ß (0.329), whereas PWV (0.188) was greater than cPP (0.123) and StO2max (-0.018). Stepwise linear regression indicated that age was the only significant predictor but removing age from the model suggested both PWV and cPP significantly (R2=0.235, p<0.001) predicted cognition. CONCLUSION: Age was the strongest predictor of cognition but is unmodifiable. However, our results indicate that central, macrovascular targets associated with aging may be a more advantageous focus for interventions than peripheral microvasculature targets to improve cognitive function. This aligns with previous studies showing end-organ (i.e., brain) damage resulting from excessive pulse velocity propagation. Future clinical trials are necessary to unravel the most potent exercise interventions for alleviating elevated arterial stiffness and cPP.

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