Selective executive impairments as neuroimmunological manifestations of the human immunodeficiency virus

Konstantinopoulou, Eleni; Ioannidis, Panagiotis; Kiosseoglou, Grigorios; Aretouli, Eleni · 2021 · Crossref

DOI: 10.31083/j.jin2003058

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Summary

This study investigates the specific nature of executive function (EF) impairments in adults living with HIV (ALWH), aiming to clarify which executive processes are selectively affected by the virus. While neurocognitive impairment is common in ALWH, particularly in the era of combined antiretroviral therapy (cART), the precise executive domains involved remain unclear due to methodological limitations in prior research, such as reliance on single tests and the presence of confounding comorities. The authors sought to determine if HIV infection causes selective deficits in updating/working memory, inhibition, or set-shifting, independent of other pathological conditions. The researchers conducted a case-control study involving 105 seropositive adults and 62 seronegative healthy controls, all aged 22–50 years without psychiatric history, substance abuse, or other medical comorbidities. Participants underwent a comprehensive battery of 11 neuropsychological tests assessing executive functions, including computerized tasks from the NIH-EXAMINER battery and traditional paper-and-pencil tests. Data were reduced using Principal Components Analysis (PCA) to empirically derive component scores summarizing performance in updating, inhibition, and set-shifting. Group differences in these component scores were analyzed using Analysis of Variance (ANOVA), controlling for demographic variables and mood state, as measured by the Depression, Anxiety, and Stress Scale (DASS). The PCA yielded a three-component solution accounting for 50.2% of the variance, labeled as updating/working memory, inhibition, and set-shifting. The updating component was primarily defined by tests measuring verbal and visual information manipulation (Dot Counting, Digit Span, Letter-Number Sequencing), while inhibition and set-shifting components were defined by their respective specialized tasks. Statistical analysis revealed that ALWH performed significantly worse than controls on the updating/working memory component ($p < 0.001$, medium-to-large effect size). In contrast, no significant group differences were found for inhibition or set-shifting components. Although ALWH reported higher levels of depression, anxiety, and stress, these mood differences did not account for the selective executive deficit. The findings indicate that HIV infection is associated with a selective impairment in the updating/working memory process, even in young to middle-aged individuals without comorbidities or diagnosed neurocognitive disorders. This suggests that updating difficulties constitute a direct neuroimmunological manifestation of HIV, distinct from deficits in inhibition or set-shifting, which may be more influenced by confounding factors like substance abuse. The study highlights the importance of using data-driven, multi-test approaches to delineate the specific cognitive profile of HAND, providing evidence that working memory updating is a central and early executive deficit in HIV infection.

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• executive function