Use of Neuroimaging to Inform Optimal Neurocognitive Criteria for Detecting HIV-Associated Brain Abnormalities

Abstract

Objective:Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.Method:Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.Results:When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.Conclusions:The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.

HIV-Associated Structural and Functional Brain Alterations in Homosexual Males

“…Even with the success of combination antiretroviral therapy (cART), various neurological complications caused by the infiltration of the human immunodeficiency virus (HIV) in the central nervous system (CNS) (1), especially HIV-associated neurocognitive disorder (2), remain a heavy disease burden. Neuroimaging is a vital tool to provide insight into structural, functional, and molecular changes occurring in the brain and has the potential to comprehensively elucidate the pathogenesis of HIV-associated neurocognitive disorder (3,4). Structural magnetic resonance imaging (sMRI) studies of HIV-infected (HIV+) individuals have found widespread brain atrophy and volume reduction in the subcortical structures including caudate nucleus, putamen, amygdala, thalamus, hippocampus, and parahippocampus (5)(6)(7)(8), and cerebellar (9,10).…”

Altered Gray Matter Volume and Functional Connectivity in Human Immunodeficiency Virus-Infected Adults

“…Neuroimaging is a promising approach to assess brain morphometric and functional changes that shows broad application prospects in the diagnosis and management of PLWH and may have the potential to shed light on the pathogenesis of HAND ( Clifford and Ances, 2013 ; Saylor et al, 2016 ; Campbell et al, 2019 ). Previous structural MRI studies indicated that PLWH display widespread brain atrophy in the subcortical nucleus as well as the frontal, parietal, occipital, temporal, and cerebellar cortices and cortical thinning in the frontal and temporal lobes and cingulate cortex ( Wilson et al, 2015 ; Underwood et al, 2017 ; Sanford et al, 2018a , b ; Israel et al, 2019 ; Hassanzadeh-Behbahani et al, 2020 ).…”

Infectious disorders: HIV, hepatitis C, and COVID-19 pandemics.

“…Studies with more limited test batteries show inconsistent findings and are likely to misclassify rates of HIV-related neurocognitive impairment and/or decline. This issue of misclassification is compounded when impairment is defined by low performance in a single domain (increased false positive rate) or when more stringent impairment thresholds of 1.5 or 2 SD below the mean are applied (increased false negative rate) despite evidence that a -1 SD cutoff optimally balances sensitivity and specificity for HIV-related CNS injury (Campbell et al, 2020;Cherner et al, 2002;Saloner & Cysique, 2017).…”