Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

Abstract

Background: The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient- reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.

Methods: Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.

Results: The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment ( P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres ( P < .05), as well as smaller brain volumes ( P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.

Conclusion: Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.

Keywords: HIV; cognitive impairment; multivariate; neuroimaging.

Figure 1.

Patient Reported Outcome Measures (PROMs) from the POPPY Study by Definition of Impairment. A, Radar plots by definition of impairment. Distances from the center represent the concordance (c-statistic) between those with cognitive impairment and the various patient reported outcome measures. B, Jitter and boxplots of Short Form Health Survey (SF-36) summary health scores by definition of impairment. P-values were calculated with the Wilcoxon rank-sum test. CI indicates cognitive impairment; CES-D, Center for Epidemiologic Studies Depression scale; HAND, HIV-associated neurocognitive dysfunction (‘Frascati’ criteria); GDS, global deficit score; IADL, instrumental activities of daily living; NMM, novel multivariate method; PHQ-9, Patient Health Questionnaire-9, SF-36, Short Form Health Survey.

Figure 2.

Radar Plots of Neuroimaging Measures by Definition of Impairment. Distances from the center represent standardized differences in the mean (ie, effect sizes) between those with and those without impairment, adjusted for age, intracranial volume, scanner, and comorbidity status (comorbidity status for CHARTER study only). HAND indicates HIV-associated neurocognitive dysfunction (‘Frascati’ criteria); FA, fractional anisotropy; GDS, global deficit score; GM, grey matter; MD, mean diffusivity; NMM, novel multivariate method; PAD, predicated age difference; WM, white matter.

Figure 3.

Grey Matter Voxel-based Morphometry Analysis of the CHARTER Cohort Showing Areas of Grey Matter Atrophy Associated with Cognitive Impairment Defined Using the Novel Multivariate Method. Areas with significantly (P < .05) lower grey matter volume in those with impairment vs no impairment defined by the NMM-colored by the t-statistic, corrected for multiple comparisons (threshold-free cluster enhancement) and adjusted for age, intracranial volume, scanner, and comorbidity status (comorbidity status for CHARTER study only). Statistical image overlaid on MNI152 T1.