Higher Cystatin C Levels Are Associated With Neurocognitive Impairment in Older HIV+ Adults

Abstract

Objective The study aims to determine whether cystatin C is associated with HIV disease and HIV-associated neurocognitive impairment (NCI). Methods Participants included 124 (HIV+ n = 77; HIV− n = 47) older adults (age ≥ 50 years) examined at the UCSD HIV Neurobehavioral Research Program. Cystatin C, a biomarker of kidney functioning that has been linked to poor health outcomes, was measured in blood. Participants completed a comprehensive neurocognitive assessment that was used to define both global and domain NCI. Results The HIV+ group had significantly higher cystatin C concentrations than the HIV− group (d=0.79 p<0.001). Among HIV+ participants, those with NCI had higher cystatin C concentrations than those without NCI (d=0.42, p=0.055), particularly among participants taking tenofovir (d=0.78, p=0.004). A receiver-operator characteristic curve identified that cystatin C levels ≥ 0.75 mg/L were associated with NCI in the HIV+ group. Using this binary variable and including relevant covariates, multivariate modeling confirmed that NCI was associated with higher cystatin C levels (OR = 3.0; p = 0.03). Conclusions Our results confirm that HIV+ older adults have higher cystatin C than HIV− older adults and further identify that cystatin C may be associated with NCI in this population, particularly if they use tenofovir. This blood biomarker may be a useful clinical tool to identify older HIV+ persons at greater risk for cognitive decline.

Plasma Cystatin C Associates With HIV-Associated Neurocognitive Disorder but Is a Poor Diagnostic Marker in Antiretroviral Therapy–Treated Individuals

“…Among older PWH who were viralogically suppressed on ART (age ≥50 years, pVL <50 copies HIV-RNA/mL), higher plasma cystatin C levels previously associated with a trend toward increased odds of NCI, in a cross-sectional analysis of a single-center study from the United States (17). Cystatin C levels were moderately discriminatory as a diagnostic marker for NCI in that study, wherein levels of at least 0.75 mg/L corresponded with a sensitivity of 61% and a specificity of 66% for NCI.…”

“…Cystatin C varies less by age, sex and muscle mass than creatinine and is more sensitive for detecting mild to moderate glomerular filtration decrements. Plasma cystatin C levels predicted cardiovascular events and mortality better than serum creatinine-based GFR estimates in the general population, and was associated with cognitive impairment in selected populations (9)(10)(11)(12)(13)(14)(15)(16), including PWH receiving viralogically suppressive ART (17).…”

The Role of Adipokines in the Pathologies of the Central Nervous System

“…Decreased levels of CSF cystatin C have been linked to rapidly progressive dementia, suggesting that lower levels may indicate a higher susceptibility for AD [7]. However, contrasting findings indicate that cystatin C levels are actually elevated in HIV-positive patients with neurocognitive impairment (NCI) compared to those without, possibly due to complications related to chronic kidney disease [8]. Nevertheless, more research is needed to fully understand this relationship.…”