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. 2022 Nov 14:26:100560.
doi: 10.1016/j.bbih.2022.100560. eCollection 2022 Dec.

Plasma biomarkers of vascular dysfunction uniquely relate to a vascular-risk profile of neurocognitive deficits in virally-suppressed adults with HIV

Rowan Saloner  1 , Ni Sun-Suslow  2 , Erin E Morgan  2 , Judith Lobo  2 , Mariana Cherner  2 , Ronald J Ellis  2 , Robert K Heaton  2 , Igor Grant  2 , Scott L Letendre  2 , Jennifer E Iudicello  2 ; TMARC Group
Affiliations

Plasma biomarkers of vascular dysfunction uniquely relate to a vascular-risk profile of neurocognitive deficits in virally-suppressed adults with HIV

Rowan Saloner et al. Brain Behav Immun Health. .

Abstract

Objective: Chronic inflammation and vascular dysfunction (e.g., chronic endothelial activation) are related yet dissociable mechanisms of HIV-associated neurocognitive impairment (NCI), even among those on antiretroviral therapy (ART). However, how these mechanisms differentially contribute to domain-specific deficits in people with and without HIV (PWH, PWoH) is unclear. We empirically-derived profiles of NCI and examined relationships with peripheral inflammatory and vascular biomarkers.

Methods: Participants were 84 virally-suppressed PWH and 126 PWoH who underwent neuropsychological testing and blood draw. Cluster analysis identified subgroups based on domain deficit scores. ANOVAs examined HIV serostatus and cluster group differences in composite plasma biomarker z-scores of inflammation (IL-6, CXCL10/IP-10, CCL2/MCP-1) and vascular injury (VCAM-1, ICAM-1, uPAR). Confirmatory regressions examined the interaction of HIV and biomarker z-scores on domain-specific T-scores, controlling for cardiovascular disease (CVD) risk and psychosocial factors.

Results: Cluster analysis identified three groups: Unimpaired (n = 129), Learning/Recall (n = 52, isolated learning/recall deficits), Dysexecutive/Slow (n = 29, executive function, working memory, processing speed, and motor deficits). PWH had higher odds of Dysexecutive/Slow membership, which related to CVD risk and higher vascular dysfunction, but not inflammation, in PWH. Vascular biomarkers moderated adverse HIV effects on executive function, processing speed, and working memory such that PWH had lower T-scores only when vascular dysfunction was high.

Conclusions: In PWH with controlled disease, peripheral markers of endothelial dysfunction and vascular permeability are selectively associated with an empirically-derived subgroup that exhibits domain deficits commonly impacted by cerebrovascular disease. Findings support the presence of a vascular NCI subgroup of PWH who may benefit from interventions that directly target the neurovascular unit.

Keywords: Cluster analysis; Endothelial dysfunction; Executive function; HIV-Associated neurocognitive disorder; IP-10; Inflammation; MCP-1; Processing speed; VCAM-1; Vascular dementia.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Neurocognitive cluster profiles by deficit scores (panel A) and rate of impairment (i.e., deficit score>0.5; panel B). Cluster analysis revealed three distinct cognitive subtypes: Unimpaired (n = 129), Learning/Recall (n = 52), and Dysexecutive/Slow (n = 29).
Fig. 2
Fig. 2
Vascular and inflammation biomarkers by cluster group (A: full sample; B: PWoH; C: PWH). #p < .10, *p < .05, **p < .01.
Fig. 3
Fig. 3
Interactive effects of HIV and vascular z-scores on neurocognition (A: executive function; B: processing speed; C: working memory). Higher vascular biomarker levels were selectively associated with worse cognition in PWH, but not PWoH.
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