Arterial stiffness mediates the association between age and processing speed at low levels of microvascular function in humans across the adult lifespan

The function of micro- and macro-vessels within the peripheral vasculature has been identified as a target for the investigation of potential cardiovascular-based promoters of cognitive decline. However, little remains known regarding the interaction of the micro- and macrovasculature as it relates to cognitive function, especially in cognitively-healthy individuals. Therefore, our purpose was to unravel peripheral factors that contribute to the association between age and processing speed. Ninety-nine individuals (51 men, 48 women) across the adult lifespan (19-81 years) were used for analysis. Arterial stiffness was quantified as carotid-femoral pulse-wave velocity (cfPWV) and near-infrared spectroscopy assessed maximal tissue oxygenation (StO 2max ) following a period of ischemia. Processing speed was evaluated with Trail Making Test (TMT) Parts A and B. Measures of central (cPP) and peripheral pulse pressure (pPP) were also collected. Moderated mediation analyses were conducted to determine contributions to the age and processing speed relation, and first-order partial correlations were used to assess associations while controlling for the linear effects of age. A p≤0.05 was considered statistically significant. At low levels of StO 2max , there was a significant positive (b=1.92;p=0.005) effect of cfPWV on time to completion on TMT Part A. Additionally, cPP (p=0.028) and pPP (p=0.027) remained significantly related to Part A when controlling for age. These results suggested that the peripheral microvasculature may be a valuable target for delaying cognitive decline, especially in currently cognitively-healthy individuals. Further, we reinforced current evidence that pulse pressure is a key endpoint for trials aimed at preventing or delaying the onset of cognitive decline.