Age-related decline in peripheral vascular health predicts cognitive impairment

Preclinical studies demonstrate that generalized endothelial cell dysfunction and microvascular impairment are potentially reversible causes of age-related vascular cognitive impairment and dementia (VCID). The present study was designed to test the hypothesis that severity of age-related macro- and microvascular dysfunction measured in the peripheral circulation is an independent predictor of cognitive performance in older adults. In this study, we enrolled 63 healthy individuals into young (<45years old) and aged (>65years old) groups. We used principal component analysis (PCA) to construct a comprehensive peripheral vascular health index (VHI) encompassing peripheral microvascular reactivity, arterial endothelial function, and vascular stiffness, as a marker of aging-induced generalized vascular dysfunction. Peripheral macrovascular and microvascular endothelial function were assessed using flow-mediated dilation (FMD) and laser speckle contrast imaging tests. Pulse waveform analysis was used to evaluate the augmentation index (AIx), a measure of arterial stiffness. Cognitive function was measured using a panel of CANTAB cognitive tests, and PCA was then applied to generate a cognitive impairment index (CII) for each participant. Aged subjects exhibited significantly impaired macrovascular endothelial function (FMD, 5.6 +/- 0.7% vs. 8.3 +/- 0.6% in young, p=0.0061), increased arterial stiffness (AIx 29.3 +/- 1.8% vs 4.5 +/- 2.6% in young, p<0.0001), and microvascular dysfunction (2.8 +/- 0.2 vs 3.4 +/- 0.1-fold change of perfusion in young, p=0.032). VHI showed a significant negative correlation with age (r=-0.54, p<0.0001) and CII significantly correlated with age (r=0.79, p<0.0001). VHI significantlycorrelated with the CII (r=-0.46, p=0.0003). A decline in peripheral vascular health may reflect generalized vascular dysfunction and predict cognitive impairment in older adults.