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.

Keywords: Cognition; Frascati criteria; HIV-associated neurocognitive disorders; Infectious disease; Magnetic resonance imaging; Magnetic resonance spectroscopy.

Figure 1.

Distribution of subjects per group using Frascati Clinical Rating vs. Meyer Criteria. Note. Frascati(Un)/Meyer(Un)=Unimpaired by both criteria; Frascati(Imp)/Meyer(Un)= Impaired by Frascati criteria and Unimpaired by Meyer; Frascati(Imp)/Meyer(Imp)=Impaired by both criteria. HAND subtypes defined using Frascati criteria: ANI = asymptomatic neurocognitive impairment; MND = mild neurocognitive disorder; HAD = HIV-associated dementia.

Figure 2.

Distribution of subjects per group using GDS vs. Meyer Criteria. Note. Depicts number of participants that were previously Frascati(Imp)/Meyer(Un) via Frascati vs. Meyer Criteria and are GDS(Un)/Meyer(Un) via GDS vs. Meyer Criteria (n=30) and those that were Frascati(Un)/Meyer(Un) via Frascati vs. Meyer Criteria and GDS(Un)/Meyer(Un) via GDS vs. Meyer criteria (n=2).

Figure 3.

Neuropsychological impairment rates by Clinical Rating (CR; Frascati) vs. Meyer group. Note. Frascati(Un)/Meyer(Un)=Unimpaired by both criteria; Frascati(Imp)/Meyer(Un)= Impaired by Frascati CR criteria and Unimpaired by Meyer; Frascati(Imp)/Meyer(Imp)=Impaired by both criteria. Impairment defined as a CR ≥ 5. *Domain not included in Meyer criteria

Figure 4.

Neuropsychological impairment rates by GDS vs. Meyer group. GDS(Un)/Meyer(Un)=Unimpaired by both Meyer and GDS criteria; GDS(Imp)/Meyer(Un)= Impaired by GDS criteria and Unimpaired by Meyer; GDS(Imp)/Meyer(Imp)=impaired by both criteria. Note. Impairment defined as a domain deficit score (DDS) > 0.5 *Domain not included in Meyer criteria

Figure 5.

Predicted means with error bars denoting standard error for cortical gray matter volume (log), sulcal CSF volume (log), and frontal gray matter choline for the Frascati CR vs. Meyer groups. Note. Un/Un=Unimpaired by both criteria; Imp/Un=Impaired by Frascati CR criteria and Unimpaired by Meyer; Imp/Imp=Impaired by both criteria; adj. d= adjusted Cohen’s d. The Frascati(Imp)/Meyer(Un) group had less cortical gray matter, greater sulcal CSF volume, and greater FGM choline than the Frascati(Un)/Meyer(Un) group. The Frascati(Imp)/Meyer(Un) group did not significantly differ from the Frascati(Imp)/Meyer(Imp) group on these measures.

Figure 6.

Predicted means with error bars denoting standard error for cortical gray matter volume (log) and frontal white matter creatine for the GDS vs. Meyer groups. Note. Un/Un=Unimpaired by both Meyer and GDS criteria; Imp/Un=Impaired by GDS criteria and Unimpaired by Meyer; Imp/Imp=impaired by both criteria; adj. d= adjusted Cohen’s d. The GDS(Imp)/Meyer(Un) group had less cortical gray matter and less FGM choline than the GDS(Un)/Meyer(Un) group. The GDS(Imp)/Meyer(Un) group did not significantly differ from the GDS(Imp)/Meyer(Imp) group on these measures.