Regional Brain Structural Dysmorphology in Human Immunodeficiency Virus Infection: Effects of Acquired Immune Deficiency Syndrome, Alcoholism, and Age

Pfefferbaum, Adolf; Rosenbloom, Margaret J.; Sassoon, Stephanie A.; Kemper, Carol A.; Deresinski, Stanley C.; Rohlfing, Torsten; Sullivan, Edith V.

doi:10.1016/j.biopsych.2012.02.018

Cited by 85 publications

(80 citation statements)

References 86 publications

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“…Consistent with our results, associations between imaging markers of cerebral atrophy and neurocognitive impairment have been previously reported in both naive and ART-experienced patients [34][35][36]. However, in our study, the association between an atrophy measurement, higher GCA score, and cognitive function was limited to those with symptomatic impairment.…”

Section: Discussionsupporting

confidence: 80%

Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial

Arenas‐Pinto

Stöhr

Jäger³

et al. 2016

Clin Infect Dis.

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Background. To determine whether treatment with ritonavir-boosted protease inhibitor (PI) monotherapy is associated with detrimental effects on neurocognitive function or brain imaging markers compared to standard antiretroviral therapy (ART).Methods. Neuropsychological assessment and brain magnetic resonance imaging were performed at the last study visit in a subset of participants randomized to PI monotherapy (PI-mono group) or ongoing triple ART (OT group) in the PIVOT trial. We calculated a global z-score (NPZ-7) from the average of the individual test z-scores and the proportion of participants with symptomatic neurocognitive impairment (score >1 standard deviation below normative means in ≥2 cognitive domains and neurocognitive symptoms). In a subgroup, white matter hyperintensities, bicaudate index, global cortical (GCA) and medial temporal lobe atrophy scores and single voxel (basal ganglia) N-acetylaspartate (NAA)/Choline, NAA/Creatine and myo-inositol/Creatine ratios were measured.Results. 146 participants (75 PI-mono) had neurocognitive testing (median time after randomization 3.8 years), of whom 78 were imaged. We found no difference between arms in NPZ-7 score (median −0.4 (interquartile range [IQR] = −0.7; 0.1) vs −0.3 (IQR = −0.7; 0.3) for the PI-mono and OT groups respectively, P = .28), the proportion with symptomatic neurocognitive impairment (13% and 18% in the PI-mono and OT groups respectively; P = .41), or any of the neuroimaging variables (P > .05). Symptomatic neurocognitive impairment was associated with higher GCA score (OR = 6.2 per additional score; 95% confidence interval, 1.7-22.3 P = .005) but no other imaging variables.Conclusions. Based on a comprehensive neuropsychological assessment and brain imaging, PI monotherapy does not increase the risk of neurocognitive impairment in stable human immunodeficiency virus-positive patients.

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Section: Discussionsupporting

confidence: 80%

Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial

Arenas‐Pinto

Stöhr

Jäger³

et al. 2016

Clin Infect Dis.

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“…Mounting evidence indicates that HIV and alcohol synergistically worsen neurocognitive function and brain integrity (Fama et al , 2009; Green et al , 2004; Pfefferbaum et al , 2005; Pfefferbaum et al , 2007; Pfefferbaum et al , 2006; Pfefferbaum et al , 2012). Our novel preliminary findings specific to elderly HIV+ individuals provide important information for clinicians when considering the potential long-term neurocognitive impact of heavy alcohol use, which may not become apparent until much later in life, despite refraining from alcohol abuse for many years.…”

Section: Discussionmentioning

confidence: 99%

“…While the impact of HIV disease and alcoholism on the brain is each well established (Grant, 1987; Heaton et al , 1995), relatively few studies have examined their combined effects on neurocognitive and brain abnormalities. Available studies conducted in young and middle-age cohorts have indicated adverse synergistic effects on structural and metabolic brain integrity, in addition to neurocognitive function involving working and episodic memory, verbal reasoning, and reaction time (Fama et al , 2009; Green et al , 2004; Moore et al , 2014; Pfefferbaum et al , 2005; Pfefferbaum et al , 2007; Pfefferbaum et al , 2006; Pfefferbaum et al , 2012). Existing findings in seronegative adults with alcoholism indicate increased risk of abnormal neurocognitive and brain alterations with older age (Oscar-Berman and Marinkovic, 2007), while such relationships remain to be examined in the context of HIV disease.…”

Section: Introductionmentioning

confidence: 99%

A history of alcohol dependence augments HIV-associated neurocognitive deficits in persons aged 60 and older

et al. 2014

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Background Excessive alcohol use is common among people living with HIV. Given the growing prevalence of older HIV+ adults, and observations indicating higher risk for neurocognitive impairment in older adults with either HIV infection or alcoholism, an increased understanding of their combined impact in the context of this increasingly aged population is crucial. Methods We conducted comprehensive neurocognitive assessment in 112 older HIV+ individuals aged 50 to 69 years. Regression analyses were conducted to examine the interaction between age and the presence of lifetime alcohol dependence on neurocognitive measures, controlling for years of education, hepatitis C serostatus, and lifetime non-alcohol substance use disorder. Results Significant interactions of age and alcohol dependence history were found for global neurocognitive function, which was driven by the domains of executive function, processing speed, and semantic memory. Follow-up analyses indicated adverse effects of alcohol use history on neurocognitive measures that were evident only in HIV+ individuals 60 years and older. Conclusions While mounting evidence in younger cohorts indicates adverse synergistic HIV/alcohol effects on neurocognitive function, our novel preliminary findings in this elderly HIV+ cohort demonstrated the importance of even a relatively distant alcohol use history on the expression of HIV-associated neurocognitive disorders that may not become apparent until much later in life.

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“…Poorer neurocognitive performance has been associated with smaller brain volumes [22,37,39–46] and greater viral burden. In addition, impaired immune response (nadir CD4+ T lymphocyte counts) has been associated with greater atrophy [20,38,40,41,46–49]*. Cortical brain atrophy and expansion of the third ventricle has been observed soon after seroconversion [50].…”

Section: Structural Neuroimaging- Volumetrics and Diffusion Tensor Immentioning

confidence: 99%

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

Ances

Hammoud

2014

Current Opinion in HIV and AIDS

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Purpose of review HIV enters the brain after initial infection, and with time can lead to HIV associated neurocognitive disorders (HAND). While the introduction of combination antiretroviral therapy (cART) has reduced the more severe forms of HAND, milder forms are still highly prevalent. The “gold standard” for HAND diagnosis remains detailed neuropsychological performance (NP) testing but additional biomarkers (including neuroimaging) may assist in early detection of HAND. Recent findings We review the application of recently developed non-invasive magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques in HIV+ individuals. In particular, magnetic resonance spectroscopy (MRS) may be more sensitive than conventional MRI alone in detecting HIV associated changes. Diffusion tensor imaging (DTI) has become increasingly popular for assessing changes in white matter structural integrity due to HIV. Both functional MRI and PET have been limitedly performed but could provide keys for characterizing neuropathophysiologic changes due to HIV. Summary It is hoped that continued progress will allow novel neuroimaging methods to be included in future HAND management guidelines.

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Regional Brain Structural Dysmorphology in Human Immunodeficiency Virus Infection: Effects of Acquired Immune Deficiency Syndrome, Alcoholism, and Age

Cited by 85 publications

References 86 publications

Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial

Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial

A history of alcohol dependence augments HIV-associated neurocognitive deficits in persons aged 60 and older

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

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