Neurocognitive impairment is associated with lower health literacy among persons living with HIV infection.

This study sought to determine the effects of HIV-associated neurocognitive disorders (HAND) on health literacy, which encompasses the ability to access, understand, appraise, and apply health-related information. Participants included 56 HIV seropositive individuals, 24 of whom met Frascati criteria for HAND, and 24 seronegative subjects who were comparable on age, education, ethnicity, and oral word reading. Each participant was administered a brief battery of well-validated measures of health literacy, including the Expanded Numeracy Scale (ENS), Newest Vital Sign (NVS), Rapid Estimate of Adult Literacy in Medicine (REALM), and Brief Health Literacy Screen (BHLS). Results revealed significant omnibus differences on the ENS and NVS, which were driven by poorer performance in the HAND group. There were no significant differences on the REALM or the BHLS by HAND status. Among individuals with HAND, lower scores on the NVS were associated with greater severity of neurocognitive dysfunction (e.g., working memory and verbal fluency) and self-reported dependence in activities of daily living. These preliminary findings suggest that HAND hinders both fundamental (i.e., basic knowledge, such as numeracy) and critical (i.e., comprehension and application of healthcare information) health literacy capacities, and therefore may be an important factor in the prevalence of health illiteracy. Health literacy-focused intervention may play an important role in the treatment and health trajectories among persons living with HIV infection

Verbal fluency in HIV infection: A meta-analytic review

Given the largely prefrontostriatal neuropathogenesis of HIV-associated neurobehavioral deficits, it is often presumed that HIV infection leads to greater impairment on letter versus category fluency. A meta-analysis of the HIV verbal fluency literature was conducted (k = 37, n = 7110) to assess this hypothesis and revealed generally small effect sizes for both letter and category fluency, which increased in magnitude with advancing HIV disease severity. Across all studies, the mean effect size of category fluency was slightly larger than that of letter fluency. However, the discrepancy between category and letter fluency dissipated in a more conservative analysis of only those studies that included both tests. Thus, HIV-associated impairments in letter and category fluency are of similar magnitude, suggesting that mild word generation deficits are evident in HIV, regardless of whether traditional letter or semantic cues are used to guide the word search and retrieval process (JINS, 2007, 13, 183–189.

Elevated Biomarkers of Inflammation and Vascular Dysfunction Are Associated with Distal Sensory Polyneuropathy in People with HIV

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178–448) and 643 (502–839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42–21.00], and 15.16 [1.07–215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration

Additive effects of aging and HIV infection on category verbal fluency: an analysis of component processes

Advances in the management of HIV infection have resulted in a growing population of older adults living with HIV. Both aging and HIV infection have been independently associated with central nervous system changes and corresponding declines in neurocognitive functioning. Poorer semantic verbal fluency output is also common in both HIV infection and healthy older adults, although, the possible additive effects of these risk factors are unknown. The present study aimed to examine the combined effects of aging and HIV on semantic verbal fluency and its component processes (i.e., clustering and switching), the neurocognitive correlates of clustering and switching in older HIV-infected adults, and the associations between clustering and switching and everyday functioning. Participants included 257 individuals across 4 demographically matched groups: Younger (i.e., <40 years) Healthy (n=93), Younger HIV-infected (n=50), Older (i.e., [greater than or equal to]50 years) Healthy (n=51), and Older HIV-infected (n=63) individuals. Participants were administered a standard semantic fluency protocol scored according to established clustering and switching guidelines (Troyer et al., 1997) and a selfreported assessment of everyday functioning as part of a comprehensive neuropsychological, medical, and psychological evaluation. Jonckheere-Terpstra tests revealed a significant stepwise additive effect between the groups for overall semantic fluency output (p = 0.004) and a trend for declining switching performance (p = 0.056), but not cluster size (p = 0.826), with greatest deficits evident in the Older HIV-infected participants. Results were not better explained by confounding psychiatric, medical, or HIV disease characteristics. Within the older HIV-infected adults, poorer switching was associated with deficits in learning and executive functioning and selfreported declines in everyday functioning. Results suggest that HIV infection and aging may confer adverse additive effects on the executive components of semantic fluency (i.e., switching), which was associated with poorer everyday functioning outcomes and may be driven by the combined frontostriatal neuropathological burden of these two conditions. This research provides preliminary insight into the cognitive architecture of HIV-associated neurocognitive disorders among older adults, and may ultimately guide rehabilitation efforts aimed at improving overall quality of life for the growing population of older adults living with HIV infectio

Additive effects of aging and HIV infection on category verbal fluency : an analysis of component processes

Advances in the management of HIV infection have resulted in a growing population of older adults living with HIV. Both aging and HIV infection have been independently associated with central nervous system changes and corresponding declines in neurocognitive functioning. Poorer semantic verbal fluency output is also common in both HIV infection and healthy older adults, although, the possible additive effects of these risk factors are unknown. The present study aimed to examine the combined effects of aging and HIV on semantic verbal fluency and its component processes (i.e., clustering and switching), the neurocognitive correlates of clustering and switching in older HIV-infected adults, and the associations between clustering and switching and everyday functioning. Participants included 257 individuals across 4 demographically matched groups: Younger (i.e., <40 years) Healthy (n=93), Younger HIV-infected (n=50), Older (i.e., [greater than or equal to]50 years) Healthy (n=51), and Older HIV-infected (n=63) individuals. Participants were administered a standard semantic fluency protocol scored according to established clustering and switching guidelines (Troyer et al., 1997) and a selfreported assessment of everyday functioning as part of a comprehensive neuropsychological, medical, and psychological evaluation. Jonckheere-Terpstra tests revealed a significant stepwise additive effect between the groups for overall semantic fluency output (p = 0.004) and a trend for declining switching performance (p = 0.056), but not cluster size (p = 0.826), with greatest deficits evident in the Older HIV-infected participants. Results were not better explained by confounding psychiatric, medical, or HIV disease characteristics. Within the older HIV-infected adults, poorer switching was associated with deficits in learning and executive functioning and selfreported declines in everyday functioning. Results suggest that HIV infection and aging may confer adverse additive effects on the executive components of semantic fluency (i.e., switching), which was associated with poorer everyday functioning outcomes and may be driven by the combined frontostriatal neuropathological burden of these two conditions. This research provides preliminary insight into the cognitive architecture of HIV-associated neurocognitive disorders among older adults, and may ultimately guide rehabilitation efforts aimed at improving overall quality of life for the growing population of older adults living with HIV infectio

Soluble Biomarkers of Cognition and Depression in Adults with HIV Infection in the Combination Therapy Era.

Purpose of reviewCognitive impairment and depression continue to be common among people with HIV (PWH) in the combination antiretroviral therapy (ART) era. A better understanding of the biological mechanisms that may underpin these disorders is needed. The purpose of this review is to describe published findings on soluble biomarkers from blood and cerebrospinal fluid (CSF) that have been associated with either cognition or depression among PWH in the setting of ART.Recent findingsSeveral biomarkers, including those that reflect viral persistence, monocyte/macrophage activation, and other processes, are associated with cognition and depressive symptoms. Some but not all results have been consistent across multiple studies. More research has been published on biomarkers of cognition relative to biomarkers of depression (particularly from CSF). More studies are needed that investigate multiple biomarkers to understand the role of distinct but additive pathways in these disorders and to guide the development of new therapies

Frailty and HIV disease severity synergistically increase risk of HIV-associated Neurocognitive Disorders.

BACKGROUND:Frailty disproportionally affects people with HIV (PWH) and increased frailty in this already vulnerable population is associated with worse neurocognitive functioning. Whether frailty interacts with current and modifiable markers of HIV disease severity to synergistically increase risk for HIV-Associated Neurocognitive Disorders (HAND), however, is unknown and important for informing the clinical care of aging PWH. SETTING:UC San Diego's HIV Neurobehavioral Research Program METHODS:: Participants were 178 people with HIV (PWH) evaluated between 2014 and 2019. HIV disease severity was measured by current CD4 count and plasma HIV RNA. HAND diagnoses were made according to the Frascati criteria using a seven-domain neuropsychological battery and the Fried Phenotype criteria was used to assess frailty syndrome (0 to 5 symptoms). The independent and interactive effects of frailty and current HIV disease severity (i.e., CD4 count and plasma HIV RNA) on HAND were examined using multiple logistic regression. RESULTS:There was an interaction between CD4 count and frailty on HAND. Simple slopes showed that CD4 count and the likelihood of HAND were negatively associated at >1.25 symptoms of frailty, and conversely, that frailty and HAND were negatively associated at 642 or less cells/mm. There was no significant independent or interactive effects of plasma HIV RNA and frailty on the likelihood of HAND. CONCLUSIONS:In addition to monitoring CD4 count, assessing for frailty may be critical in older adults with HIV to potentially mitigate poor neurobehavioral outcomes. Longitudinal follow-up studies are needed to determine the directionality of these findings

Frailty and HIV disease severity synergistically increase risk of HIV-associated Neurocognitive Disorders.

BACKGROUND:Frailty disproportionally affects people with HIV (PWH) and increased frailty in this already vulnerable population is associated with worse neurocognitive functioning. Whether frailty interacts with current and modifiable markers of HIV disease severity to synergistically increase risk for HIV-Associated Neurocognitive Disorders (HAND), however, is unknown and important for informing the clinical care of aging PWH. SETTING:UC San Diego's HIV Neurobehavioral Research Program METHODS:: Participants were 178 people with HIV (PWH) evaluated between 2014 and 2019. HIV disease severity was measured by current CD4 count and plasma HIV RNA. HAND diagnoses were made according to the Frascati criteria using a seven-domain neuropsychological battery and the Fried Phenotype criteria was used to assess frailty syndrome (0 to 5 symptoms). The independent and interactive effects of frailty and current HIV disease severity (i.e., CD4 count and plasma HIV RNA) on HAND were examined using multiple logistic regression. RESULTS:There was an interaction between CD4 count and frailty on HAND. Simple slopes showed that CD4 count and the likelihood of HAND were negatively associated at >1.25 symptoms of frailty, and conversely, that frailty and HAND were negatively associated at 642 or less cells/mm. There was no significant independent or interactive effects of plasma HIV RNA and frailty on the likelihood of HAND. CONCLUSIONS:In addition to monitoring CD4 count, assessing for frailty may be critical in older adults with HIV to potentially mitigate poor neurobehavioral outcomes. Longitudinal follow-up studies are needed to determine the directionality of these findings