Reduction in cerebral oxygen metabolism in subcortical regions may be a biomarker of cognitive decline in people living with human immunodeficiency virus

Abstract

Background and purpose: Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO₂ ) in whole brain, white matter, gray matter and lenticular nuclei were studied in people living with human immunodeficiency virus (PLHIV) as well as HIV-associated neurocognitive disorder (HAND).

Methods: Treatment-naïve PLHIV underwent neurocognitive assessment and magnetic resonance (MR) measurement of rCBF and rCMRO₂ with repeat after 12 months of antiretroviral therapy (ART). Age- and sex-matched controls underwent single MR measurements. Regional CBF and rCMRO₂ were compared amongst symptomatic, asymptomatic, normal HAND and controls using analysis of variance. Longitudinal analysis of HAND worsening (≥1 category) was assessed after 12 months of ART and correlated with rCBF and rCMRO₂ measured by MR imaging using the paired-sample t test.

Results: Thirty PLHIV completed baseline and 12-month assessments (29 with rCMRO₂ measurement). At baseline HAND assessment, 13% had no cognitive impairment, 27% had asymptomatic neurocognitive impairment, 60% had mild neurocognitive disorder and none had HIV-associated dementia. At 12 months, 13% had no cognitive impairment, 20% had asymptomatic neurocognitive impairment, 50% had mild neurocognitive disorder and 17% had HIV-associated dementia. In those without HAND worsening (N = 21) rCMRO₂ remained stable and in those with HAND worsening (N = 8) rCMRO₂ measurement declined from baseline to 12 months in white matter (2.05 ± 0.40 to 1.73 ± 0.51, p = 0.03) and lenticular nuclei (4.32 ± 0.39 to 4.00 ± 0.51, p = 0.05).

Conclusions: In recently diagnosed PLHIV, no association was found between rCBF or rCMRO₂ and cognitive impairment at baseline. There was a reduction in rCMRO₂ in those with worsening of cognitive function at 12 months on ART. Reduction in rCMRO₂ may be a biomarker of cognitive decline in PLHIV.

Keywords: HAND; HIV; antiretroviral therapy; cerebral blood flow; cerebral oxygen metabolism.

FIGURE 1

Progression of HAND category between baseline and 12 months

FIGURE 2

MAP, CBF, CMRO₂ and HAND at baseline control and in ART-naïve PLHIV

FIGURE 3

MAP, CBF, CMRO₂ and HAND at baseline control and in PLHIV after 12 months of ART

FIGURE 4

MAP, CBF and CMRO₂ at baseline and at 12 months in PLHIV with worse HAND classification at 12 months (N = 8)

FIGURE 5

MAP, CBF and CMRO₂ at baseline and at 12 months in PLHIV with stable HAND classification at 12 months (N = 22 for CBF and N = 21 for CMRO₂)