Cerebrovascular Disease Correlates With Longitudinal Brain Atrophy in Virally Suppressed Older People Living With HIV

Samboju, Vishal; Cobigo, Yann; Paul, Robert; Naasan, Georges; Hillis, Madeline; Tsuei, Torie; Javandel, Shireen; Valcour, Victor; Milanini, Benedetta

doi:10.1097/qai.0000000000002683

Cited by 11 publications

(12 citation statements)

References 52 publications

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“…Due to earlier onset and progression of vascular disease, PWH are also at increased risk for vascular cognitive impairment (VCI) at younger ages compared with the general population [10,19]. Given evidence that VCI contributes to cognitive impairment in PWH on ART [17,20,21], vascular disease has emerged as a significant contributing factor to HAND in the current ART era [10,19,[22][23][24][25]. Accordingly, biomarkers that can distinguish VCI from other causes of cognitive impairment will be useful for diagnosis and clinical management.…”

Section: Introductionmentioning

confidence: 99%

Vascular injury markers associated with cognitive impairment in people with HIV on suppressive antiretroviral therapy

Guha,

Misra,

Yin

et al. 2023

Aids

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Objective: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain prevalent despite viral suppression on antiretroviral therapy (ART). Vascular disease contributes to HAND, but peripheral markers that distinguish vascular cognitive impairment (VCI) from HIV-related etiologies remain unclear. Design: Cross-sectional study of vascular injury, inflammation, and central nervous system (CNS) injury markers in relation to HAND. Methods: Vascular injury (VCAM-1, ICAM-1, CRP), inflammation (IFN-γ, IL-1β, IL-6, IL-8, IL-15, IP-10, MCP-1, VEGF-A), and CNS injury (NFL, total Tau, GFAP, YKL-40) markers were measured in plasma and CSF from 248 individuals (143 HIV+ on suppressive ART and 105 HIV- controls). Results: Median age was 53 years, median CD4 count, and duration of HIV infection were 505 cells/μl and 16 years, respectively. Vascular injury, inflammation, and CNS injury markers were increased in HIV+ compared with HIV- individuals (p<0.05). HAND was associated with increased plasma VCAM-1, ICAM-1, and YKL-40 (p < 0.01) and vascular disease (p = 0.004). In contrast, inflammation markers had no significant association with HAND. Vascular injury markers were associated with lower neurocognitive T scores in age-adjusted models (p < 0.01). Furthermore, plasma VCAM-1 correlated with NFL (r = 0.29, p = 0.003). Biomarker clustering separated HAND into three clusters: two clusters with high prevalence of vascular disease, elevated VCAM-1 and NFL, and distinctive inflammation profiles (CRP/ICAM-1/YKL-40 or IL-6/IL-8/IL-15/MCP-1), and one cluster with no distinctive biomarker elevations. Conclusions: Vascular injury markers are more closely related to HAND and CNS injury in PWH on suppressive ART than inflammation markers and may help to distinguish relative contributions of VCI to HAND.

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Section: Introductionmentioning

confidence: 99%

Vascular injury markers associated with cognitive impairment in people with HIV on suppressive antiretroviral therapy

Guha,

Misra,

Yin

et al. 2023

Aids

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“…Despite prior reports that HIV disease confers an elevated risk of WMH, 19–23 the pathophysiology remains uncertain. Consistent with other studies, 20,23,46,47 we found no relationship between WMH and HIV disease characteristics, such as time since diagnosis and CD4 counts of immune function.…”

Section: Discussionmentioning

confidence: 98%

“…Participants reported frequency of smoking in the past 3 months. As in prior studies, 21,42,63 a composite CVD risk score was calculated as the sum of the following risk factors: diabetes, hyperlipidemia, hypertension, CVD diagnosis, obesity (BMI ≥ 30), and current smoking. Total scores ranged from 0 to 6.…”

Section: Clinical Datamentioning

confidence: 99%

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Cocaine use is associated with cerebral white matter hyperintensities in HIV disease

Meade

Bell

Towe

et al. 2023

Ann Clin Transl Neurol

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BackgroundWhite matter hyperintensities (WMH), a marker of cerebral small vessel disease and predictor of cognitive decline, are observed at higher rates in persons with HIV (PWH). The use of cocaine, a potent central nervous system stimulant, is disproportionately common in PWH and may contribute to WMH.MethodsThe sample included of 110 PWH on antiretroviral therapy. Fluid‐attenuated inversion recovery (FLAIR) and T1‐weighted anatomical MRI scans were collected, along with neuropsychological testing. FLAIR images were processed using the Lesion Segmentation Toolbox. A hierarchical regression model was run to investigate predictors of WMH burden [block 1: demographics; block 2: cerebrovascular disease (CVD) risk; block 3: lesion burden].ResultsThe sample was 20% female and 79% African American with a mean age of 45.37. All participants had persistent HIV viral suppression, and the median CD4+ T‐cell count was 750. Nearly a third (29%) currently used cocaine regularly, with an average of 23.75 (SD = 20.95) days in the past 90. In the hierarchical linear regression model, cocaine use was a significant predictor of WMH burden (β = .28). WMH burden was significantly correlated with poorer cognitive function (r = −0.27). Finally, higher WMH burden was significantly associated with increased serum concentrations of interferon‐γ‐inducible protein 10 (IP‐10) but lower concentrations of myeloperoxidase (MPO); however, these markers did not differ by COC status.ConclusionsWMH burden is associated with poorer cognitive performance in PWH. Cocaine use and CVD risk independently contribute to WMH, and addressing these conditions as part of HIV care may mitigate brain injury underlying neurocognitive impairment.

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“…As already mentioned, the early introduction of cART (practically immediately after seropositivity con rmation) resulted in the prolonged lifespan of PLWH and more prevalent non-HIV related disorders in this population. Among those, the most important are those associated with systemic in ammationmetabolic syndrome, hepatic steatosis/non-alcoholic liver disease, and cardiovascular disorders [3][4][5][6]24].…”

Section: Discussionmentioning

confidence: 99%

Additive effect of metabolic syndrome on brain atrophy in people living with HIV – magnetic resonance volumetry study

Andric

Marić

Bulovic

et al. 2023

Preprint

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With people living with HIV (PLWH) reaching senium, the importance of aging-related comorbidities such as metabolic syndrome (MS) becomes increasingly important. The aim of this study was to determine the additive effect of MS on brain atrophy in PLWH. This prospective study included 43 PLWH, average age 43.02 ± 10.93 years and 24 healthy controls, average age 36.87 ± 8.89 years. PLWH were divided into two subgroups: without MS and with MS, according to NCEP-ATP-III criteria. All patients underwent brain magnetic resonance (MR)imaging on 3T clinical scanner with MR volumetry, used for defining volumes of cerebrospinal fluid (CSF) spaces and white and grey matter structures, including basal ganglia. ANOVA was used to determine differences in brain volumes between subject subgroups. Binary classification was performed to determine sensitivity and specificity of volumetry findings and cut-off values. Statistical significance was set at p < 0.05. PLWH presented with significantly lower volumes of gray matter, putamen, thalamus, globus pallidus and nc. accumbens compared to healthy controls; cut-off values were: for gray matter 738.130 cm3, putamen 8.535cm3, thalamus 11.895 cm3, globus pallidus 2.252 cm3 nc. accumbens 0.715 cm3. Volumes of CSF and lateral ventricles were higher in PLWH with MS compared to those without MS- with specificity of 0.310 and sensitivity of 0.714 it can be assumed that PLWH with CSF volume above 212.83cm3 will also have MS. There seems to be an important connection between MS and brain volume reduction in PLWH with MS, which may add to accurate identification of persons at risk of developing HIV-associated cognitive impairment.

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Cerebrovascular Disease Correlates With Longitudinal Brain Atrophy in Virally Suppressed Older People Living With HIV

Cited by 11 publications

References 52 publications

Vascular injury markers associated with cognitive impairment in people with HIV on suppressive antiretroviral therapy

Vascular injury markers associated with cognitive impairment in people with HIV on suppressive antiretroviral therapy

Cocaine use is associated with cerebral white matter hyperintensities in HIV disease

Additive effect of metabolic syndrome on brain atrophy in people living with HIV – magnetic resonance volumetry study

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