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

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 University of California, San Diego 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.

Frailty Characteristics in Chronic HIV Patients are Markers of White Matter Atrophy Independently of Age and Depressive Symptoms: A Pilot Study.

BACKGROUND: Chronic HIV disease is associated with neurocognitive impairment and age-related conditions such as frailty. OBJECTIVE: To determine whether regional brain volumetric changes correlate with frailty parameters in older (≥ 40 years) HIV+ patients on stable combination antiretroviral therapy. METHOD: Thirty-five HIV-infected participants in the Hawaii Aging with HIV Cohort - Cardiovascular Disease study underwent T1-weighted brain magnetic resonance imaging, frailty assessment and neuropsychological testing. Five physical frailty traits were assessed: low physical activity; exhaustion; unintentional weight loss; weak hand grip strength; slow walking speed. Linear regression quantified cross-sectional relationships of 12 brain regions to walking times and hand grip strength. RESULTS: Participants were 50.6 ± 6.8 years old and 77% had undetectable plasma viral load. One subject was frail (possessing ≥ 3 frailty traits); 23% were pre-frail (1-2 frailty traits) and had worse composite learning and memory z-scores than did non-frail individuals (p=0.06). Pre-frail or frail subjects had reduced hand grip strength relative to the non-frail group (p=0.001). Longer walking times (slower gait) related independently to lower volumes of cerebellar white matter (p<0.001, ß=-0.6) and subcortical gray matter (p<0.05, ß=-0.30). Reduced thalamus volume was linked to weaker grip strength (p < 0.05, ß=0.4). Caudate volume was negatively associated with grip strength (p<0.01, ß=-0.5). CONCLUSION: Volumetric changes in cerebellar white matter and subcortical gray matter, brain regions involved in motor control and cognition, may be connected to frailty development in well-controlled HIV. Gait speed is particularly sensitive to white matter alterations and should be investigated as a predictor of frailty and brain atrophy in chronically infected patients.