The relationship between vascular endothelial growth factor (VEGF) and amnestic mild cognitive impairment among older adults living with HIV

Vanessa B Serrano,Robert K Heaton,Erin E Sundermann,David J Moore,Jessica L Montoya,Jennifer Iudicello,Scott Letendre,Laura M Campbell

doi:10.1007/s13365-021-01001-y

Vanessa B Serrano, Robert K Heaton + Show 6 more

Open Access

https://doi.org/10.1007/s13365-021-01001-y

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Abstract

Older people with HIV (PWH) experience increased risk of age-related neurodegenerative disorders and cognitive decline, such as amnestic mild cognitive impairment (aMCI). The objective of this study was to examine the relationship between aMCI and plasma VEGF biomarkers among older PWH. Data were collected at a university-based research center from 2011 to 2013. Participants were 67 antiretroviral therapy-treated, virally suppressed PWH. Participants completed comprehensive neurobehavioral and neuromedical evaluations. aMCI status was determined using adapted Jak/Bondi criteria, classifying participants as aMCI + if their performance was > 1 SD below the normative mean on at least two of four memory assessments. VEGF family plasma biomarkers (i.e., VEGF, VEGF-C, VEGF-D, and PIGF) were measured by immunoassay. Logistic regression models were conducted to determine whether VEGF biomarkers were associated with aMCI status. Participants were mostly non-Hispanic white (79%) men (85%) with a mean age of 57.7 years. Eighteen (26.9%) participants met criteria for aMCI. Among potential covariates, only antidepressant drug use differed by aMCI status, and was included as a covariate. VEGF-D was significantly lower in the aMCI + group compared to the aMCI − group. No other VEGF levels (VEGF, VEGF-C, PIGF) differed by aMCI classification (ps > .05). In a sample of antiretroviral therapy-treated, virally suppressed PWH, lower levels of VEGF-D were associated with aMCI status. Longitudinal analyses in a larger and more diverse sample are needed to support VEGF-D as a putative biological marker of aMCI in HIV.

Highlights

Half of people with HIV (PWH) are aged 50 and older (National Institute on Aging 2020), and the population of older PWH is expected to increase given the widespread use of effective antiretroviral therapy (ART; Centers for Disease Control and Prevention 2016)
vascular endothelial growth factor (VEGF) has been associated with HIV-associated neurocognitive disorder (HAND) in the context of HIV disease (Kallianpur et al 2019), it is unknown whether VEGF levels differ across older PWH with and without amnestic mild cognitive impairment (aMCI)
To explore this association further, we examined whether antidepressant class [i.e., atypical, selective serotonin reuptake inhibition (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), and tricyclic] or specific antidepressant were statistically associated with aMCI status (Table 4)

Summary

Introduction

Evidence suggests that amnestic MCI (aMCI; i.e., mild memory deficits regardless of other cognitive domain performance; Kremen et al 2014) is more closely associated with a higher risk of progression to AD dementia than non-amnestic MCI (Bradfield et al 2018; Damian et al 2013; Whitwell et al 2008). Higher VEGF levels have been associated with optimal brain aging (i.e., higher hippocampal volume and less hippocampal atrophy/cognitive decline over time; Hohman et al 2015), among individuals showing early hallmarks of the AD cascade (e.g., elevated levels of tau), as well as better memory and language performance among individuals already diagnosed with AD (Alvarez et al 2018). VEGF has been associated with HAND in the context of HIV disease (Kallianpur et al 2019), it is unknown whether VEGF levels differ across older PWH with and without aMCI

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