Abnormal Cerebral Perfusion Profile in Older Adults with HIV-Associated Neurocognitive Disorder: Discriminative Power of Arterial Spin-Labeling

Abstract

Background and purpose: The aging HIV-infected (HIV⁺) population has increased vascular comorbidities, including stroke, and increased cognitive deficits compared with the general population. Arterial spin-labeling is a technique to measure cerebral blood flow and is more sensitive than regional volume loss in assessing neurodegenerative diseases and cognitive aging. Previous studies have found global cerebral perfusion abnormalities in the HIV⁺ participants. In this study, we evaluated the specific regional pattern of CBF abnormalities in older HIV⁺ participants using quantitative whole-brain arterial spin-labeling.

Materials and methods: CBF data from the UCSF HIV Over 60 Cohort and the Alzheimer Disease Neuroimaging Initiative were retrospectively evaluated to identify 19 HIV⁺ older adults, all with plasma viral suppression (including 5 with HIV-associated neurocognitive disorder); 13 healthy, age-matched controls; and 19 participants with early mild cognitive impairment. CBF values were averaged by ROI and compared among the 3 groups using generalized linear models.

Results: When we accounted for age, education, sex, and vascular risk factors, the HIV⁺ participants demonstrated alterations in regional cerebral perfusion, including hypoperfusion of bilateral temporal, parietal, and occipital brain regions compared with both clinically healthy participants and those with mild cognitive impairment. Arterial spin-labeling showed reasonable test characteristics in distinguishing those with HIV-associated neurocognitive disorder from healthy controls and participants with mild cognitive impairment.

Conclusions: This study found specific CBF patterns associated with HIV status despite viral suppression-data that should animate further investigations into the pathobiologic basis of vascular and cognitive abnormalities in HIV-associated neurocognitive disorders.

Fig 1.

Odds ratio from the GLMnet model averaged over 500 bootstrap iterations. Reductions in CBF in bilateral temporal, occipital, and posterior cingulate regions best distinguish HIV⁺ participants from HC (blue, hypoperfusion). This same pattern of reduced CBF distinguishes HIV⁺ from MCI, while the latter shows comparative reductions in frontal CBF (red, hyperperfusion in HIV⁺ participants relative to MCI).

Fig 2.

Odds ratios for each brain region and confounding factors in the GLMnet model, obtained by exponentiating the model coefficients averaged over a bootstrap (500 iterations). The regions used in the model in >25% bootstrap iterations are highlighted in blue for the region hypoperfused in HIV⁺ participants and in red for regions hyperperfused in HIV⁺ participants compared with HC or those with MCI. HIV⁺ participants demonstrate relative hypoperfusion in bilateral temporal and occipital regions and relative frontoinsular hyperperfusion.

Fig 3.

Histogram of the frequency distribution of accuracy, sensitivity, and specificity over the bootstrap (500 iterations) for the proposed GLMnet models.