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Vascular Contributions to Neurocognitive Impairment among Older Persons with HIV

Abstract

HIV-associated neurocognitive impairment (NCI) is highly prevalent in the modern era of combination antiretroviral therapy, and older persons (50 years and older) are particularly vulnerable to the burden of HIV-associated NCI. In addition, cardiovascular disease is increasingly observed in HIV. Three studies were conducted to investigate the association between markers of vascular risk and NC function among persons living with HIV/AIDS.

For all three studies, participants completed standardized neurobehavioral and neuromedical assessments. NC function was evaluated using a well-validated comprehensive battery. The first study evaluated the relationships among markers of vascular remodeling, arterial stiffness (measured by pulse pressure, PP), and NC function among older HIV-seropositive (HIV+; n = 72) and HIV-seronegative (n = 36) adults. A biomarker of vascular remodeling was associated with greater PP and worse NC function. PP had a quadratic relationship with NC function, such that lower and higher PP values, relative to the entire sample mean, were associated with worse NC function. These findings indicate that vascular remodeling may contribute to arterial stiffening and changes in PP, which, in turn, deleteriously affect NC function. The second study assessed the impact of disturbances in coagulation on NC function in the same cohort of older HIV+ and HIV-seronegative adults. Coagulation moderated the effect of HIV on NC function, such that greater coagulation imbalance was associated with poorer NC function among HIV+ participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers. These findings indicate that procoagulation may exert a detrimental effect on NC function among older HIV+ adults. Lastly, the third study aimed to examine the association between visit-to-visit variability in blood pressure (BPV) and NC change in a well-characterized HIV+ cohort (N = 533). BPV was not significantly associated with rate of NC change; however, baseline PP was a significant predictor of rate of NC change. These findings suggest that arterial stiffness might be a crucial factor impacting NC function over time among HIV+ adults.

The findings of these studies indicate that vascular remodeling, arterial stiffening, and procoagulation may contribute to poorer NC outcomes among HIV+ persons. Biomarkers of vascular processes may provide valuable information regarding the prognosis and risk stratification of HIV+ adults for NCI.

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