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      HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis

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          Abstract

          Objective:

          While some reports suggest that HIV+ individuals continue to display executive function (EF) impairment in the era of cART, findings have been contradictory and appear to differ based on the aspect of EF being measured. To improve the understanding of how discrete executive abilities may be differentially affected or spared in the context of HIV-infection, we conducted a systematic review and meta-analysis to (a) determine whether and to what extent HIV+ adults experience deficits in EFs, and (b) understand how demographic and clinical characteristics may modify the associations between HIV-infection and executive abilities.

          Method:

          Studies comparing HIV+ and HIV-uninfected groups on measures of working memory, set-shifting, inhibition, decision-making, and apathy between 2000 and 2017 were identified from three databases. Effect sizes (Cohen’s d) were calculated using inverse variance weighted random effects models. Meta-regression was used to examine the moderating effect of demographic and clinical variables.

          Results:

          Thirty-seven studies (n = 3,935 HIV+; n = 2,483 HIV-uninfected) were included in the meta-analysis. Pooled effect sizes for deficits associated with HIV-infection were small for domains of set-shifting ( d = −0.34, 95% CI: −0.47, −0.20) and inhibition ( d = −0.31, 95% CI: −0.40, −0.21), somewhat larger for measures of decision-making ( d = −0.41, 95% CI: −0.53, −0.28) and working memory ( d = −0.42, 95% CI: −0.59, −0.29), and largest for apathy ( d = −0.87, 95% CI: −1.09, −0.66). Meta-regression demonstrated that age, sex, education, current CD4 count, and substance dependence differentially moderated the effects of HIV-infection on specific EFs. However, lower nadir CD4 count was the only variable associated with greater deficits in nearly all EF domains.

          Conclusions:

          Our results suggest that discrete domains of EF may be differentially affected by HIV-infection and moderating demographic and clinical variables. These findings have implications for the development of targeted cognitive remediation strategies.

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          Most cited references90

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          The Nature and Organization of Individual Differences in Executive Functions: Four General Conclusions.

          Executive functions (EFs)-a set of general-purpose control processes that regulate one's thoughts and behaviors-have become a popular research topic lately and have been studied in many subdisciplines of psychological science. This article summarizes the EF research that our group has conducted to understand the nature of individual differences in EFs and their cognitive and biological underpinnings. In the context of a new theoretical framework that we have been developing (the unity/diversity framework), we describe four general conclusions that have emerged from our research. Specifically, we argue that individual differences in EFs, as measured with simple laboratory tasks, (1) show both unity and diversity (different EFs are correlated yet separable); (2) reflect substantial genetic contributions; (3) are related to various clinically and societally important phenomena; and (4) show some developmental stability.
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            Individual differences in executive functions are almost entirely genetic in origin.

            Recent psychological and neuropsychological research suggests that executive functions--the cognitive control processes that regulate thought and action--are multifaceted and that different types of executive functions are correlated but separable. The present multivariate twin study of 3 executive functions (inhibiting dominant responses, updating working memory representations, and shifting between task sets), measured as latent variables, examined why people vary in these executive control abilities and why these abilities are correlated but separable from a behavioral genetic perspective. Results indicated that executive functions are correlated because they are influenced by a highly heritable (99%) common factor that goes beyond general intelligence or perceptual speed, and they are separable because of additional genetic influences unique to particular executive functions. This combination of general and specific genetic influences places executive functions among the most heritable psychological traits. These results highlight the potential of genetic approaches for uncovering the biological underpinnings of executive functions and suggest a need for examining multiple types of executive functions to distinguish different levels of genetic influences. (c) 2008 APA, all rights reserved
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              Dimensions of executive functioning: Evidence from children

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                Author and article information

                Journal
                8502170
                4628
                J Clin Exp Neuropsychol
                J Clin Exp Neuropsychol
                Journal of clinical and experimental neuropsychology
                1380-3395
                1744-411X
                8 September 2018
                09 July 2017
                May 2018
                01 May 2019
                : 40
                : 4
                : 357-376
                Affiliations
                [1 ]Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [2 ]Department of Psychiatry, University of California San Diego, 9500 Gilman Dr. La Jolla, CA 92093
                Author notes
                Corresponding Author: Keenan Walker, PhD, Kwalke26@ 123456jhmi.edu , Department of Neurology, Johns Hopkins Hospital, Phipps 446, 600 North Wolfe St., Baltimore, MD 21287, T: 626-840-6216, F: 410-955-0672
                Gregory Brown, PhD, gbrown@ 123456ucsd.edu , Department of Psychiatry, University of San Diego, California, 3350 La Jolla Village Dr., San Diego, CA 92161, T: 858-642-3166
                Article
                PMC6164174 PMC6164174 6164174 nihpa1505281
                10.1080/13803395.2017.1349879
                6164174
                28689493
                9b77d6d6-4e8a-4d11-ad19-5bbfea0ad12b
                History
                Categories
                Article

                Frontal lobe,Executive functioning,HIV-associated neurocognitive disorder,Neuropsychological functioning,HIV/AIDS

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