BackgroundChronic HIV disease is associated with neurocognitive impairment and age-related conditions such as frailty.ObjectiveTo determine whether regional brain volumetric changes correlate with frailty parameters in older (≥ 40 years) HIV+ patients on stable combination antiretroviral therapy.MethodThirty-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.ResultsParticipants 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, β=−0.6) and subcortical gray matter (p<0.05, β=−0.30). Reduced thalamus volume was linked to weaker grip strength (p < 0.05, β=0.4). Caudate volume was negatively associated with grip strength (p<0.01, β=−0.5).ConclusionVolumetric 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.

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.

A 67-year-old right-handed woman presented with progressive dizziness and nausea. She had a history of high-grade serous ovarian carcinoma with extension into the colon, diagnosed one and a half years prior. She had previously undergone chemotherapy and sigmoid resection with total abdominal hysterectomy and bilateral salpingo-oophorectomy. She also had a history of type 2 diabetes mellitus complicated by peripheral neuropathy.