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Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC). NVC responses depend on healthy microvascular endothelial function. PAD is associated with significant endothelial dysfunction in peripheral arteries, but its effect on NVC responses has not been investigated. This study was designed to test the hypothesis that NVC and peripheral microvascular endothelial function are impaired in PAD. We enrolled 11 symptomatic patients with PAD and 11 age- and sex-matched controls. Participants were evaluated for cognitive performance using the Cambridge Neuropsychological Test Automated Battery and functional near-infrared spectroscopy to assess NVC responses during the cognitive n-back task. Peripheral microvascular endothelial function was evaluated using laser speckle contrast imaging. We found that cognitive performance was compromised in patients with PAD, evidenced by reduced visual memory, short-term memory, and sustained attention. We found that NVC responses and peripheral microvascular endothelial function were significantly impaired in patients with PAD. A positive correlation was observed between microvascular endothelial function, NVC responses, and cognitive performance in the study participants. Our findings support the concept that microvascular endothelial dysfunction and neurovascular uncoupling contribute to the genesis of cognitive impairment in older PAD patients with claudication. Longitudinal studies are warranted to test whether the targeted improvement of NVC responses can prevent or delay the onset of PAD-associated cognitive decline. NEW & NOTEWORTHY Peripheral artery disease (PAD) was associated with significantly decreased cognitive performance, impaired neurovascular coupling (NVC) responses in the prefrontal cortex (PFC), left and right dorsolateral prefrontal cortices (LDLPFC and RDLPFC), and impaired peripheral microvascular endothelial function. A positive correlation between microvascular endothelial function, NVC responses, and cognitive performance may suggest that PAD-related cognitive decrement is mechanistically linked, at least in part, to generalized microvascular endothelial dysfunction and subsequent impairment of NVC responses.

Background. Aging is a major risk factor for a range of chronic diseases. Oxidative stress theory of aging has been previously proposed as one of the mechanisms responsible for the age-related decline in organ/tissue function and the development of age-related diseases. Urine contains rich biological information on the health status of every major organ system and can be an important noninvasive source for biomarkers of systemic oxidative stress in aging. Aims. The objective of this cross-sectional study was to validate a novel panel of urinary oxidative stress biomarkers. Methods. Nucleic acid oxidation adducts and oxidative damage markers of lipids and proteins were assessed in urine samples from nondiabetic and currently nonsmoking subjects ( n = 198 ) across different ages (20 to 89 years old). Urinary parameters and chronological age were correlated then the biological age of enrolled individuals was determined from the urinary oxidative stress markers using the algorithm of Klemera and Doubal. Results. Our findings showed that 8-oxo-7,8-deoxyguanosine (8-oxoG), 8-oxo-7,8-dihydroguanosine (8-OHdG), and dityrosine (DTyr) positively correlated with chronological age, while the level of an F2-isoprostane (iPF2α-VI) correlated negatively with age. We found that 8-oxoG, DTyr, and iPF2α-VI were significantly higher among accelerated agers compared to nonaccelerated agers and that a decision tree model could successfully identify accelerated agers with an accuracy of >92%. Discussion. Our results indicate that 8-oxoG and iPF2α-VI levels in the urine reveal biological aging. Conclusion. Assessing urinary biomarkers of oxidative stress may be an important approach for the evaluation of biological age by identifying individuals at accelerated risk for the development of age-related diseases.