Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy

Mukerji, Shibani S.; Locascio, Joseph J.; Misra, Vikas; Lorenz, David R.; Holman, Alex; Dutta, Anupriya; Penugonda, Sudhir; Wolinsky, Steven M.; Gabuzda, Dana

doi:10.1093/cid/ciw495

Cited by 32 publications

(30 citation statements)

References 39 publications

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“…In a combined multivariable analysis of the entire cohort, we found that higher HDL was associated with lower odds of cognitive impairment, which parallels results from studies in the general population [38,39]. Contrary to our results, however, time-varying higher HDL attenuated the rate of cognitive decline in men living with HIV from the Multicenter AIDS Cohort Study [40].…”

Section: Discussionsupporting

confidence: 70%

Physical Activity Is Associated With Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection

Chow

Makanjuola

et al. 2018

The Journal of Infectious Diseases

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Section: Discussionsupporting

confidence: 70%

Physical Activity Is Associated With Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection

Chow

Makanjuola

et al. 2018

The Journal of Infectious Diseases

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“…The results of this study need to be interpreted in the light of several limitations. The results of several investigations into the genetic contributions to HAND suggest that the harmful effects of ApoE ε4 on cognitive function may be likely to be expressed at a later age (Valcour et al 2004;Pomara et al 2008;Panos et al 2013;Mukerji et al 2016;López et al 2017). Such a temporally mediated effect could explain some of the divergent literature findings regarding the role of ApoE in HAND.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, ApoE may play a role in some of the pathophysiological mechanisms underlying the deleterious consequences of HIV in the brain (Corder et al 1998). Studies that have investigated the link between genetic variation in ApoE and HAND have found evidence both for (Dunlop et al 1997;Corder et al 1998;Spector et al 2010;Andres et al 2011;Hoare et al 2013;Mukerji et al 2016;Wendelken et al 2016) and against (Dunlop et al 1997;Burt et al 2008;Pemberton et al 2008;Pomara et al 2008;Sun et al 2010;Joska et al 2010;Morgan et al 2013;Becker et al 2015) its involvement in HAND. These contradictory findings may in part be due to the failure to assess the interaction of ApoE with other risk factors (Cooley et al 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, this study was conducted to examine how CT interacts with ApoE to influence neurocognitive function in HIV-positive South African women of Xhosa ethnicity. We hypothesised that carriers of the ApoE ε4 isoform would perform worse on cognitive tests, and that these deficits would be further accentuated by a history of CT. Studies have associated ApoE ε4 genotype with a range of cognitive effects in HIV including executive function, perceptual speed, verbal fluency, learning, memory and global cognitive function (Andres et al 2011;Chang et al 2011;Hoare et al 2013;Panos et al 2013;Mukerji et al 2016;Wendelken et al 2016). The interaction of CT and HIV has also been associated with a variety of cognitive impairments including diminished attention/working memory, executive function, language, motor skill and processing speed (Spies et al 2016(Spies et al , 2017Clark et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV

et al. 2018

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HIV-associated neurocognitive disorder (HAND) describes a spectrum of behavioural, motor and cognitive disturbances that can occur secondary to HIV infection. Less severe forms of the disorder persist despite advances in antiretroviral medication efficacy and availability. Childhood trauma (CT) may predispose individuals to developing HAND. As genetic variation in human apolipoprotein E (ApoE) has been implicated in cognitive decline and may mediate the development of long-term health outcomes following CT, we investigated the influence of ApoE and CT on cognitive function in the context of HIV. One hundred twenty-eight HIV-positive Xhosa women completed the Childhood Trauma Questionnaire-Short Form (CTQ-SF) as well as the HIV Neurobehavioral Research Center neurocognitive test battery. rs7412 and rs429358 were genotyped using KASP assays, and this data was used to determine the ApoE isoform. Baseline differences in demographic and clinical variables according to CT exposure were calculated. Analysis of covariance was used to assess the contributions of CT and ApoE variants, as well as their interaction, to cognitive function. Eighty-eight participants reported experiencing CT. The rs7412 C allele protected against the harmful effect of CT on motor scores using an additive model. The interaction of ApoE ε4 and CT was associated with worse attention/working memory scores. ApoE ε4, alone and in combination with CT, is associated with poorer cognitive function. Further research into this gene-environment interaction may assist in identifying at-risk individuals for targeted interventions.

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“…The APOEε4 genotype is a risk factor for elevated cholesterol in ART-adherent HIV(+) men aged >50 years [72] with a risk for a higher cognitive decline associated and cardiovascular problems.…”

Section: Hiv-1 and Risks Of Alzheimer's Disease (Ad) Pathogenesismentioning

confidence: 99%

Brain Aging in HIV-1 Infection

Santerre¹,

Sawaya²

2018

Advances in HIV and AIDS Control

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It has been shown that patients carrying HIV-1 accumulate damage to cells and tissues that are not directly infected by the virus itself (e.g., neurons). Importantly, these include changes known as HIV-Associated Neurodegenerative Disorder (HAND) leading to the loss of neuronal functions. HAND is an outstanding problem in the clinical management of HIV-1 patients because suppression of infectious virus by cART does not completely block neurodegenerative changes. Neuropsychological studies disclose cognitive alteration (such as loss of Spatial and Declarative Memory) in a substantial proportion of HIV-1 infected patients, and analysis of post-mortem brain tissues isolated from HIV-1 patients treated with cART show signs of neurodegeneration. In the absence of HIV-1 infection of neurons, several mechanisms have been proposed for HAND, including indirect inflammatory effects in the CNS and direct effects of viral proteins (e.g., gp120) shed from activated HIV-1-infected cells. The fact that these viral proteins enter the neurons through several pathways suggests the presence of many competing mechanisms that can contribute to HAND, each of which has its advocates. Their relative contributions to clinical disease in vivo remain to be sorted out, and this is an outstanding problem in HIV research. This chapter will shed some light on the mechanisms used by HIV-1 leading to memory impairments and premature brain aging.

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Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy

Cited by 32 publications

References 39 publications

Physical Activity Is Associated With Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection

Physical Activity Is Associated With Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection

Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV

Brain Aging in HIV-1 Infection

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