The Impact of Alcohol Use on Frontal White Matter in HIV

Gullett, Joseph M.; Lamb, Damon G.; Porges, Eric; Woods, Adam J.; Rieke, Jake D; Thompson, Paul M.; Jahanshad, Neda; Nir, Talia M.; Tashima, Karen T.; Cohen, Ronald A.

doi:10.1111/acer.13823

Cited by 14 publications

(13 citation statements)

References 69 publications

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“…These findings are also consistent with MRS studies that reported significant Age*HIV interactive effects, particularly for frontal WM metabolites (Cysique et al, 2013;Ernst & Chang, 2004;Harezlak et al, 2011); Age*HIV interactive effects were also reported in subcortical regions (Kuhn et al, 2018). Together, these findings both support and expand upon prior literature demonstrating jointly deleterious effects of HIV and aging on WM microstructure (Gullett et al, 2018;Holt et al, 2012;Nir et al, 2014;Towgood et al, 2012).…”

Section: Discussionsupporting

confidence: 89%

“…Similarly, as expected and consistent with a larger literature (e.g., (Chang et al, 2011;Filippi, Ulu g, Ryan, Ferrando & van Gorp, 2001;Pomara et al, 2001;Seider et al, 2016;Wang et al, 2011;Wright, Heaps, Shimony, Thomas & Ances, 2012)), a significant main effect of HIV was found on WM. However, some TOIs evidenced WM deterioration that was greater in the seronegative control group, which may be explained by frontal and temporal lobes, consistent with knowledge of a relatively heterogeneous yet typically predominantly frontal-subcortical involvement in HIV (Ettenhofer & Abeles, 2009;Gullett et al, 2018;Heaton et al, 2010;Hinkin, Castellon, Atkinson, & Goodkin, 2001;Price, Bartlett, & Bloom, 2016;Valcour et al, 2004a;Valcour, Sithinamsuwan, Letendre, & Ances, 2011). These findings are also consistent with MRS studies that reported significant Age*HIV interactive effects, particularly for frontal WM metabolites (Cysique et al, 2013;Ernst & Chang, 2004;Harezlak et al, 2011); Age*HIV interactive effects were also reported in subcortical regions (Kuhn et al, 2018).…”

Section: Discussionsupporting

confidence: 82%

“…These results indicate that in addition to older age being related to poorer WM microstructural integrity, the detrimental effect of aging on WM is significantly stronger among HIV+ individuals relative to HIV‐ individuals. In several TOIs, including the CC, ILF, IFO, and ATR, interactive effects were strongest in fibers projecting to the frontal and temporal lobes, consistent with knowledge of a relatively heterogeneous yet typically predominantly frontal‐subcortical involvement in HIV (Ettenhofer & Abeles, ; Gullett et al, ; Heaton et al, ; Hinkin, Castellon, Atkinson, & Goodkin, ; Price, Bartlett, & Bloom, ; Valcour et al, ; Valcour, Sithinamsuwan, Letendre, & Ances, ). These findings are also consistent with MRS studies that reported significant Age*HIV interactive effects, particularly for frontal WM metabolites (Cysique et al, ; Ernst & Chang, ; Harezlak et al, ); Age*HIV interactive effects were also reported in subcortical regions (Kuhn et al, ).…”

Section: Discussionsupporting

confidence: 71%

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The joint effect of aging and HIV infection on microstructure of white matter bundles

Kuhn

Jin

Huang

et al. 2019

Human Brain Mapping

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Recent evidence suggests the aging process is accelerated by HIV. Degradation of white matter (WM) has been independently associated with HIV and healthy aging. Thus, WM may be vulnerable to joint effects of HIV and aging. Diffusion‐weighted imaging (DWI) was conducted with HIV‐seropositive (n = 72) and HIV‐seronegative (n = 34) adults. DWI data underwent tractography, which was parcellated into 18 WM tracts of interest (TOIs). Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) regression was conducted assessing the joint effect of advanced age and HIV on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) along TOI fibers. In addition to main effects of age and HIV on WM microstructure, the interactive effect of age and HIV was significantly related to lower FA and higher MD, AD, and RD across all TOIs. The location of findings was consistent with the clinical presentation of HIV‐associated neurocognitive disorders. While older age is related to poorer WM microstructure, its detrimental effect on WM is stronger among HIV+ relative to HIV− individuals. Loss of WM integrity in the context of advancing age may place HIV+ individuals at increased risk for brain and cognitive compromise.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 71%

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The joint effect of aging and HIV infection on microstructure of white matter bundles

Kuhn

Jin

Huang

et al. 2019

Human Brain Mapping

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“…(Marquine et al, 2016). Neuroimaging studies suggest that alcohol use disorder (AUD) co-occurring with HIV may exacerbate certain structural brain abnormalities which can affect cognitive functioning (Lewis-de Los Angeles et al, 2017, Bladowska et al, 2013, Sullivan et al, 2011, Rosenbloom et al, 2010, Nelson et al, 2005, Pfefferbaum et al, 2005, Chang et al, 2004, Pfefferbaum et al, 2002, Durazzo et al, 2007, Cardenas et al, 2005, Meyerhoff et al, 1995, Pfefferbaum et al, 2007) (Gullett et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Heavy Alcohol Use and Age Effects on HIV‐Associated Neurocognitive Function

Cohen

Gullett

Porges

et al. 2018

Alcoholism Clin & Exp Res

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Background. There is growing concern about the health impact of heavy alcohol use in people infected with Human Immunodeficiency Virus (HIV+). Mixed findings of past studies regarding the cognitive impact of alcohol use in HIV+ adults have been mixed, with inconsistent evidence that alcohol consumption exacerbates HIV-associated brain dysfunction. This study examined contributions of current heavy drinking, lifetime AUD, and age to cognitive deficits in HIV+ adults, and relative to other HIV-associated clinical factors. Methods. Cognitive performance of HIV+ adults (n=104) was assessed and comparisons were made between heavy current to non-heavy drinkers (NIAAA criteria), lifetime AUD versus no-AUD, and older (> 50 years) vs. younger participants. Hierarchical regression analyses were conducted to examine the association between cognitive performance and current heavy drinking, lifetime AUD, and older age, while also correcting for HIV clinical factors and history of other substance use. Results. Individuals reporting current heavy drinking and meeting criteria for lifetime AUD demonstrated the greatest degree of deficits across multiple cognitive domains. Deficits were greatest among HIV+ adults with lifetime AUD, and older age was also associated with weaker cognitive performance. Lifetime AUD and older age independently exhibited stronger associations with cognitive performance than HIV clinical factors (e.g. viral load, current CD4, nadir CD4) or past opiate and cocaine use. Conclusions. Current heavy drinking and lifetime AUD adversely affect cognitive function in HIV+ adults. Greatest deficits existed when there was a history of AUD and continued current heavy drinking, indicating that past AUD continues to have an adverse impact and should not be ignored. That alcohol use was more strongly associated with cognitive performance than HIV clinical factors underscores clinical importance of targeting reduction of heavy alcohol consumption in HIV+ adults.

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“…Alcohol use disorder (AUD) among PLWH is estimated to be 2 to 4 times higher than among the general population (Duko et al, 2019; Galvan et al, 2002; Petry, 1999; Vagenas et al, 2015). AUD in PLWH adversely affects brain structural, functional, and metabolic functions, as well as cognition (Cohen et al, 2019; Gullett et al, 2018; Meyerhoff, 2001; Míguez‐Burbano et al, 2014) and therefore may be a major contributor to cognitive deficit among PLWH.…”

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confidence: 99%

Neuroimaging and Cognitive Evidence for Combined HIV‐Alcohol Effects on the Central Nervous System: A Review

Britton

Porges

Bryant

et al. 2020

Alcoholism Clin & Exp Res

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Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairment in daily life. The brain shrinkage, functional network alterations, and brain metabolite disruption seen in individuals with HIV/AUD have been attributed to several interacting pathways: viral proteins and EtOH are directly neurotoxic and exacerbate each other’s neurotoxic effects; EtOH reduces antiretroviral adherence and increases viral replication; AUD and HIV both increase gut microbial translocation, promoting systemic inflammation and HIV transport into the brain by immune cells; and HIV may compound alcohol’s damaging effects on the liver, further increasing inflammation. We additionally review the neurocognitive effects of aging, Hepatitis C coinfection, obesity, and cardiovascular disease, tobacco use, and nutritional deficiencies, all of which have been shown to compound cognitive changes in HIV, AUD, and in their comorbidity. Finally, we examine emerging questions in HIV/AUD research, including genetic and cognitive protective factors, the role of binge drinking in HIV/AUD‐linked cognitive decline, and whether neurocognitive and brain functions normalize after drinking cessation.

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The Impact of Alcohol Use on Frontal White Matter in HIV

Cited by 14 publications

References 69 publications

The joint effect of aging and HIV infection on microstructure of white matter bundles

The joint effect of aging and HIV infection on microstructure of white matter bundles

Heavy Alcohol Use and Age Effects on HIV‐Associated Neurocognitive Function

Neuroimaging and Cognitive Evidence for Combined HIV‐Alcohol Effects on the Central Nervous System: A Review

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