Metabolic Syndrome and Neurocognitive Deficits in HIV Infection

Beverly Yu, BS; Elizabeth Pasipanodya, PhD; Jessica L. Montoy; PhD; Raeanne C. Moore, PhD; Sara Gianella, MD; Allen McCutchan, MD; Ron Ellis, MD; Robert K. Heaton, PhD; Dilip V. Jeste, MD; David J. Moore, PhD; María J. Marquine, PhD

Disclosures

J Acquir Immune Defic Syndr. 2019;81(1):95-101. 

In This Article

Abstract and Introduction

Abstract

Background: The adverse consequences of HIV and related comorbidities on the central nervous system remain prevalent in the era of combination antiretroviral therapy. Metabolic syndrome (MetS) is a common comorbidity in HIV and has been linked to increased neurocognitive impairment in the general population. We investigated the association between MetS and neurocognition among persons living with HIV (PLHIV).

Methods: Participants included 109 PLHIV and 92 HIV-uninfected adults (HIV−) from the Multi-dimensional Successful Aging cohort study at the University of California San Diego (age: M = 50.8, SD = 8.0). Participants completed neuromedical, psychiatric, and neurocognitive assessments. Based on a comprehensive neurocognitive battery, we examined global neurocognitive deficits (based on the entire battery) and neurocognitive deficits in 7 domains (verbal fluency, learning, recall, executive function, working memory, speed of information processing, and fine motor skills). MetS was determined via the standard criteria by the National Cholesterol Education Program's Adult Treatment Panel-III. Covariates examined included demographics and psychiatric comorbidities (and HIV disease characteristics among PLHIV).

Results: MetS had an independent significant effect on global neurocognitive deficits among PLHIV (P = 0.03) but not among their HIV− counterparts (P = 0.93). Among PLHIV, MetS was most strongly associated with the neurocognitive domains of learning, fine motor skills, and executive function. Diabetes and elevated triglycerides were the MetS components most strongly linked with increased global neurocognitive deficits in PLHIV.

Conclusions: The present findings underscore the need for early identification of PLHIV at risk for MetS and the implementation of preventive and treatment approaches to lessen the development of MetS and neurocognitive impairment among PLHIV.

Introduction

Despite dramatic reductions in HIV-related morbidity and mortality in the era of combination antiretroviral therapy (ART), the adverse consequences of HIV and related comorbidities on the central nervous system remain prevalent, with approximately 40% of persons living with HIV (PLHIV) showing neurocognitive impairment (NCI).[1,2] Whereas these impairments are most typically mild to moderate in severity, they are important predictors of everyday functioning, such as management of medication regimen and driving.[3]

Metabolic syndrome (MetS) is also commonly present in PLHIV,[4] and it is an important predictor of neurocognitive change in the general population.[5–7] MetS is a collection of metabolic risk factors,[8] including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance/glucose intolerance, a proinflammatory state (characterized by elevated C-reactive protein), and a prothrombotic state (characterized by raised levels of plasminogen activator inhibitor-1 and fibrinogen).[9] Various criteria have been used to determine the presence of MetS. Based on the criteria by the National Cholesterol Education Program's Adult Treatment Panel III report (NCEP ATP III),[9] the overall prevalence of MetS among adults in the United States is estimated to be close to 35%,[10] with advanced age associated with increased prevalence[10,11] and some indication that HIV disease might confer an increased risk for MetS.[12–14]

MetS has been consistently associated with NCI and decline in the general population.[5–7] Specifically, it has been linked to worse executive functioning,[15–18] memory,[16,19] recall,[20] processing speed,[18] and overall intellectual functioning.[20] When the components of MetS are examined individually among HIV-uninfected persons (HIV−), hyperglycemia and hypertension tend to exhibit the strongest associations with NCI.[21,22] Among PLHIV, some of the components of MetS (ie, diabetes and central obesity) have been linked to HIV-associated NCI.[23–26] A small number of cross-sectional studies have found a significant link between diabetes and worse neurocognitive performance in PLHIV, even after adjusting for significant covariates.[24–26] A cross-sectional study on 130 PLHIV from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort found that central obesity was a significant predictor of NCI in a multivariable analysis that accounted for the impact of body mass index (BMI), triglyceride levels, self-reported diabetes, and a diagnosis of AIDS.[23] In this multivariable model, self-reported diabetes was also marginally associated with NCI but with a large odds ratio. These results indicate that at least certain components of MetS are associated with increased risk for NCI in HIV infection. It should be noted that in both of the aforementioned studies, components of MetS, as opposed to MetS as a cluster of symptoms, were analyzed for their association with neurocognitive functioning among PLHIV. No published studies to date have investigated the impact of MetS as a whole on neurocognition in HIV, which might be greater than the sum of its components' individual effects. Whether the cluster of abnormalities that comprise MetS affects HIV-associated NCI is unknown. Furthermore, although the mechanisms underlying the link between MetS and neurocognitive deficits are likely varied, at least some of these mechanisms, such as lower blood–brain barrier integrity and systemic inflammation,[21,27,28] might result in a larger impact of MetS on neurocognitive functioning among PLHIV compared with HIV− persons. This has not been explored in previous studies, however, which have not included an HIV− comparison group.[23–26]

The overall goal of our study was to examine the association between MetS (as a cluster of abnormalities[9]) and neurocognitive deficits in the context of HIV infection. Our first aim was to investigate the link between MetS and neurocognitive deficits among groups of persons with and without HIV and to assess the potentially modifying role of HIV infection on this association. We hypothesized that the association between MetS and neurocognitive deficits would be stronger among persons with HIV than among those without HIV. Our second aim was to further examine the association between MetS and neurocognitive deficits among PLHIV while accounting for the effects of other factors related to HIV-associated NCI, such as HIV disease characteristics. We hypothesized that even after accounting for these covariates, MetS would be associated with increased concurrent risk for neurocognitive deficits among PLHIV. We were also interested in exploring whether certain components of the MetS might be more strongly associated than others with neurocognitive deficits in PLHIV.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....