Single-domain antibodies reveal unique borrelicidal epitopes on the Lyme disease vaccine antigen, outer surface protein A (OspA).

Camelid-derived, single-domain antibodies (VHHs) have proven to be extremely powerful tools in defining the antigenic landscape of immunologically heterogeneous surface proteins. In this report, we generated a phage-displayed VHH library directed against the candidate Lyme disease vaccine antigen, outer surface protein A (OspA). Two alpacas were immunized with recombinant OspA serotype 1 from Borrelia burgdorferi sensu stricto strain B31, in combination with the canine vaccine RECOMBITEK Lyme containing lipidated OspA. The phage library was subjected to two rounds of affinity enrichment ("panning") against recombinant OspA, yielding 21 unique VHHs within two epitope bins, as determined through competition enzyme linked immunosorbent assays (ELISAs) with a panel of OspA-specific human monoclonal antibodies. Epitope refinement was conducted by hydrogen exchange-mass spectrometry. Six of the monovalent VHHs were expressed as human IgG1-Fc fusion proteins and shown to have functional properties associated with protective human monoclonal antibodies, including B. burgdorferi agglutination, outer membrane damage, and complement-dependent borreliacidal activity. The VHHs displayed unique reactivity profiles with the seven OspA serotypes associated with B. burgdorferi genospecies in the United States and Europe consistent with there being unique epitopes across OspA serotypes that should be considered when designing and evaluating multivalent Lyme disease vaccines.

A Systematic Review and Meta-Analysis of Social Cognition Among People Living with HIV: Implications for Non-Social Cognition and Social Everyday Functioning.

Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% experience cognitive impairment; likewise, social cognitive deficits in theory of mind, prosody, empathy, and emotional face recognition/perception are gradually being recognized. This systematic review and meta-analysis aim to summarize the current knowledge of social cognitive ability among PLHIV, identified by 14 studies focused on social cognition among PLHIV, and provides an objective consensus of the findings. In general, the literature suggests that PLHIV may be at-risk of developing subtle social cognitive deficits that may impact their everyday social functioning and quality of life. The causes of such social cognitive deficits remain unclear, but perhaps develop due to (1) HIV-related sequelae that are damaging the same neurological systems in which social cognition and non-social cognition are processed; (2) stress related to coping with HIV disease itself that overwhelms one's social cognitive resources; or (3) may have been present pre-morbidly, possibly contributing to an HIV infection. From this, a theoretical framework is proposed highlighting the relationships between social cognition, non-social cognition, and social everyday functioning.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

"As I Grew Older, My Life Got Better": Conceptions of Successful Aging among Older Women Living with or at Risk of HIV.

Successful aging (SA) is an important target for HIV care. However, we have insufficient understanding of how older women living with HIV (OWLH) in the US define SA. We explored conceptions of SA by OWLH and older women at risk of HIV and examined whether SA conceptions differed by (1) HIV serostatus, and (2) participation in the Women's Interagency HIV Study (WIHS). These analyses were part of a larger mixed-methods study with a sequential design. Participants were recruited at two clinical WIHS sites. We enrolled both WIHS participants and non-WIHS clinic patients. Our sample was 84% Black and included 29 OWLH and 15 older women at risk of HIV. We conducted 21 semi-structured interviews and four focus groups. The dataset was analyzed using descriptive, comparative, and relational analysis. We found four interlinked themes: life course perspective, accepting and celebrating aging, taking care of yourself, and looking good. The life course perspective was a core theme: participants assessed their aging in comparison to their earlier life hardships. These themes were similarly present among OWLH and older women at risk of HIV, although OWLH emphasized taking care of HIV. SA conceptualizations by OWLH did not differ whether or not they participated in the WIHS. Women living with or at risk of HIV may experience severe hardships throughout their lives. Overcoming these hardships may be linked to SA. Assessing the needs and connecting women to resources and programs are critical for SA promotion.

A 2-Year Longitudinal Randomized Control Trial of Speed of Processing Cognitive Training in Aging Adults with HIV-Associated Neurocognitive Disorder: Results of the Think Fast Study.

Nearly 40% of people with HIV (PWH) experience HIV-associated Neurocognitive Disorder (HAND). In this 3-group efficacy study, 216 PWH 40 + years with HAND or borderline HAND were randomized to either: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73), or (3) 10 h of Internet navigation training (n = 73; contact control group). Participants were administered a measure of SOP [i.e., the Useful Field of View Test (UFOV®)] at baseline, at posttest immediately after training, and at year 1 and year 2 follow up. Intent-to-treat linear mixed-effect models with subject-specific intercept and slope were fitted to estimate between-group mean differences at the follow-up time-points. At the post-intervention time-point, small beneficial SOP training effects were observed for the 10-h group in UFOV® total (d = 0.28, p = 0.002). Effects were of larger magnitude for the 20-h group in these same outcomes [UFOV® total (d = 0.43, p < 0.001)]. These results indicated better benefit with more training. No intervention effect was observed at year 1. At year 2, beneficial effects of small magnitude were observed again in the 10-h group [UFOV® total (d = 0.22, p = 0.253)] with larger small-to-moderate magnitude in the 20-h group [UFOV® total (d = 0.32, p = 0.104)]. This study suggests that SOP training can improve a key indicator of this cognitive performance and that treatment gains are small-to-moderate over a two-year period. Prior literature suggests slower SOP is predictive of impairment in everyday functioning in older PWH; such an approach could potentially improve everyday functioning in PWH.

Cerca del 40% de las personas viviendo con VIH (PVV) experimentan Trastorno Neurocognitivo Asociado al VIH (HAND, por sus siglas en inglés). En este estudio de eficacia de 3 grupos, se aleatorizó a 216 PVV mayores de 40 años de edad con HAND o HAND límite a: (1) 10 horas de entrenamiento en velocidad de procesamiento (SOP, por sus siglas en inglés) (n = 70); (2) 20 horas de entrenamiento SOP (n = 73), o (3) 10 horas de entrenamiento en navegación por Internet (n = 73; grupo control de contacto). Se administró una medida de SOP a los participantes [la Prueba de Campo de Visión Útil (UFOV®)] al inicio, inmediatamente después del entrenamiento, y en el seguimiento de año 1 y año 2. Los datos se analizaron bajo el principio de intención de tratar, utilizando modelos lineales de efectos mixtos para estimar las diferencias promedio entre grupos en los puntos de seguimiento. En el punto de tiempo de post- entrenamiento, se observaron pequeños efectos beneficiosos del entrenamiento SOP para el grupo de 10 horas en el puntaje total de UFOV® (d = 0.28, p = 0.002). Para esta misma medida, los efectos fueron de mayor magnitud en el grupo de 20 horas [UFOV® total (d = 0.43, p < 0.001)]. Estos resultados indicaron un mayor beneficio con más entrenamiento. No se observó ningún efecto de intervención en el año 1. En el año 2, se observaron efectos beneficiosos de pequeña magnitud nuevamente en el grupo de 10 horas [UFOV® total (d = 0.22, p = 0.253)] y en el grupo de 20 horas [UFOV® total (d = 0.32, p = 0.104)] con una magnitud pequeña a moderada). Este estudio confirma que el entrenamiento SOP puede mejorar un indicador clave de este rendimiento cognitivo y que las ganancias del tratamiento son pequeñas a moderadas durante un período de dos años. La literatura previa sugiere que una SOP más lenta es predictiva de deterioro en el funcionamiento diario en PVV mayores; tal enfoque podría mejorar potencialmente el funcionamiento diario en PVV.

Cognitive prescriptions for reducing dementia risk factors among Black/African Americans: feasibility, acceptability, and preliminary efficacy.

OBJECTIVES: Black/African Americans (B/AAs) have double the risk of Alzheimer's disease and related dementia than Whites, which is largely driven by health behaviors. This study examined the feasibility, acceptability, and preliminary efficacy of a pilot randomized clinical trial of an individualized multidomain health behavior intervention among middle-aged and older B/AAs (dubbed Cognitive Prescriptions [CogRx]). DESIGN: Thirty-nine community-dwelling B/AA participants aged 45-65 without significant cognitive impairment were randomized to one of three groups: CogRx, Psychoeducation, or no-contact control. The Psychoeducation and CogRx groups received material on dementia prevalence, prognosis, and risk factors, while the CogRx group additionally received information on their risk factor profile across the five CogRx domains (physical, cognitive, and social activity, diet, sleep). This information was used for developing tailored 3-month goals in their suboptimal areas. RESULTS: The CogRx program had high retention (all 13 CogRx participants completed the 3-month program and 97% of the full sample completed at least 1 follow-up) and was well-received as exhibited by qualitative and quantitative feedback. Themes identified in the positive feedback provided by participants on the program included: increased knowledge, goal-setting, personalization, and motivation. The COVID-19 pandemic was a consistent theme that emerged regarding barriers of adherence to the program. All three groups improved on dementia knowledge, with the largest effects observed in CogRx and Psychoeducation groups. Increases in cognitive, physical, and overall leisure activities favored the CogRx group, whereas improvements in sleep outcomes favored Psychoeducation and CogRx groups as compared to the control group. CONCLUSION: The CogRx program demonstrated feasibility, acceptability, and preliminary efficacy in increasing dementia knowledge and targeted health behaviors. Further refinement and testing of the implementation and effectiveness of similar person-centered dementia prevention approaches are needed on a larger scale in diverse populations. Such findings may have implications for clinical and public health recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03864536.

Chronic Pain Resilience Across Clinical Populations: A Concept Analysis.

BACKGROUND: Chronic pain resilience is a concept that is frequently used in research but lacks theoretical clarity. Understanding chronic pain resilience is germane to developing interventions to improve it and the overall quality of life among individuals with chronic pain. AIMS: To uncover and clarify the unique characteristics of the concept of chronic pain resilience. DESIGN: A concept analysis using Rodgers' evolutionary method. METHODS: Full-text articles published after 2000 in English were used to inform the concept analysis. Scopus, PubMed, PsychINFO, Embase, and CINAHL Plus with Full Text were utilized for literature searches. Rodgers' evolutionary approach was used to clarify the attributes, antecedents, and consequences. RESULTS: The search yielded 31 articles that were used in the analysis. The key attributes of chronic pain resilience included engagement in meaningful activities despite pain, maintaining positive psychological homeostasis, buffering against negative mental outcomes, seeking support, and self-empowerment. After considering surrogate terms, antecedents, attributes, and consequences, chronic pain resilience may be defined as the development of the capacity to successfully adapt to chronic pain. This adaptation results in a move toward optimal social, physical, mental, and behavioral functioning by balancing negative and positive psychosocial factors, despite the additional challenges brought about by living with chronic pain.

Self-Esteem Among U.S. African American and Latinx Adolescents With Depressive Symptoms and Overweight and/or Obesity.

PURPOSE: To examine the concept of self-esteem among African American and Latinx adolescents with overweight and/or obesity and depressive symptoms in the United States. METHOD: Using key terms in CINAHL, PubMed, and PsycINFO databases, an initial search yielded 371 articles; after examining title, abstract, and full text, 33 articles remained. The concept of adolescent self-esteem was analyzed using Rodger's evolutionary method. RESULTS: Several antecedents of self-esteem in this context were identified, including bullying, negative portrayal in the media, stressors and hassles, low socioeconomic status, dieting, and family dietary influences. Attributes identified were body image and misperception, body image dissatisfaction, diminished social status, and isolation. Consequences included stigma, somatic complaints, decreased earnings over a lifetime, decreased quality of life, lower educational attainment over a lifetime, and increased substance use. Increased self-esteem, increased number of friends, and in-depth friendships were associated with a lower risk of being overweight or obese. CONCLUSION: Adolescent self-esteem varied based on gender, racial and ethnic group, and changed over time in the African American population but remained static in the Latinx population. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

Structural Basis of Antibody-Mediated Inhibition of Ricin Toxin Attachment to Host Cells.

Monoclonal antibodies, JB4 and SylH3, neutralize ricin toxin (RT) by inhibiting the galactose-specific lectin activity of the B subunit of the toxin (RTB), which is required for cell attachment and entry. It is not immediately apparent how the antibodies accomplish this feat, considering that RTB consists of two globular domains (D1, D2) each divided into three homologous subdomains (α, ß, γ) with the two functional galactosyl-specific carbohydrate recognition domains (CRDs) situated on opposite poles (subdomains 1α and 2γ). Here, we report the X-ray crystal structures of JB4 and SylH3 Fab fragments bound to RTB in the context of RT. The structures revealed that neither Fab obstructed nor induced detectable conformational alterations in subdomains 1α or 2γ. Rather, JB4 and SylH3 Fabs recognize nearly identical epitopes within an ancillary carbohydrate recognition pocket located in subdomain 1ß. Despite limited amino acid sequence similarity between SylH3 and JB4 Fabs, each paratope inserts a Phe side chain from the heavy (H) chain complementarity determining region (CDR3) into the 1ß CRD pocket, resulting in local aromatic stacking interactions that potentially mimic a ligand interaction. Reconciling the fact that stoichiometric amounts of SylH3 and JB4 are sufficient to disarm RTB's lectin activity without evidence of allostery, we propose that subdomain 1ß functions as a "coreceptor" required to stabilize glycan interactions principally mediated by subdomains 1α and 2γ. Further investigation into subdomain 1ß will yield fundamental insights into the large family of R-type lectins and open novel avenues for countermeasures aimed at preventing toxin uptake into vulnerable tissues and cells.

Single-domain antibodies neutralize ricin toxin intracellularly by blocking access to ribosomal P-stalk proteins.

During ricin intoxication in mammalian cells, ricin's enzymatic (RTA) and binding (RTB) subunits disassociate in the endoplasmic reticulum. RTA is then translocated into the cytoplasm where, by virtue of its ability to depurinate a conserved residue within the sarcin-ricin loop (SRL) of 28S rRNA, it functions as a ribosome-inactivating protein. It has been proposed that recruitment of RTA to the SRL is facilitated by ribosomal P-stalk proteins, whose C-terminal domains interact with a cavity on RTA normally masked by RTB; however, evidence that this interaction is critical for RTA activity within cells is lacking. Here, we characterized a collection of single-domain antibodies (VHHs) whose epitopes overlap with the P-stalk binding pocket on RTA. The crystal structures of three such VHHs (V9E1, V9F9, and V9B2) in complex with RTA revealed not only occlusion of the ribosomal P-stalk binding pocket but also structural mimicry of C-terminal domain peptides by complementarity-determining region 3. In vitro assays confirmed that these VHHs block RTA-P-stalk peptide interactions and protect ribosomes from depurination. Moreover, when expressed as "intrabodies," these VHHs rendered cells resistant to ricin intoxication. One VHH (V9F6), whose epitope was structurally determined to be immediately adjacent to the P-stalk binding pocket, was unable to neutralize ricin within cells or protect ribosomes from RTA in vitro. These findings are consistent with the recruitment of RTA to the SRL by ribosomal P-stalk proteins as a requisite event in ricin-induced ribosome inactivation.

Structure of a transmission blocking antibody in complex with Outer surface protein A from the Lyme disease spirochete, Borreliella burgdorferi.

319-44 is a human monoclonal antibody capable of passively protecting mice against tick-mediated infection with Borreliella burgdorferi, the bacterial genospecies responsible for Lyme disease in North America. In vitro, 319-44 has complement-dependent borreliacidal activity and spirochete agglutinating properties. Here, we report the 2.2 Å-resolution crystal structure of 319-44 Fab fragments in complex with Outer surface protein A (OspA), the ~30 kDa lipoprotein that was the basis of the first-generation Lyme disease vaccine approved in the United States. The 319-44 epitope is focused on OspA ß-strands 19, 20, and 21, and the loops between ß-strands 16-17, 18-19, and 20-21. Contact with loop 20-21 explains competition with LA-2, the murine monoclonal antibody used to estimate serum borreliacidal activities in the first-generation Lyme disease vaccine clinical trials. A high-resolution B-cell epitope map of OspA will accelerate structure-based design of second generation OspA-based vaccines.

Tools for Screening and Measuring Anxiety Among Women Living with HIV of Reproductive Age: A Scoping Review.

Emerging evidence suggests that women living with HIV (WLWH) may experience higher rates of anxiety than men living with HIV and women living without HIV. To date, relatively little knowledge exists on valid anxiety screening and diagnostic tools and how they are used among WLWH, specifically WLWH of reproductive age. Thus, the purpose of this scoping review was to describe what is known in the published literature about anxiety among WLWH and the tools used to measure and screen for anxiety in clinical and research contexts. The Arksey and O'Malley methodological framework was used to guide a scoping review of published articles in PsycINFO, Scopus, Sociological Abstracts, and PubMed databases. Twenty-one measures of anxiety were used across the 52 articles identified in the search. Most measures used were self-report. Inconsistencies in standardized screening tools and cutoff scores were observed across studies. Further, measures to assess anxiety varied among studies focused on WLWH. Based on the results from this review, there is a need for consistent, valid measures of anxiety to advance research and clinical practice to support the well-being of WLWH.

The Association Between Objectively-Measured Physical Activity and Cognitive Functioning in Middle-Aged and Older People Living with HIV.

Middle-aged and older people living with HIV (PWH) are at higher risk for cognitive impairment and engage in lower levels of physical activity (PA) than seronegative counterparts. Research examining the association between objectively-measured PA and cognitive function in this population is scarce. This cross-sectional study examined the association between accelerometry-measured PA and cognitive functioning among 75 PWH (mean age 55.63). Light PA was the PA variable with the most consistent associations with cognition, with more minutes per week of light PA (performed in bouts of ≥ 10 min) being associated with better executive function, working memory/attention, and speed of processing performance, adjusted for age and current CD4 count. Findings suggest that although middle-aged and older PWH engage in more light than moderate-to-vigorous PA, light PA may be beneficial to cognition. Longitudinal studies are needed to understand PA dose-response associations with cognitive trajectories, cognitive domain specificity of PA effects, and underlying neural mechanisms of PA.

Resilience in the context of dementia family caregiver mental health: A concept analysis.

Resilience has been identified as a key concept for dementia family caregiver mental health; however, the concept is not well defined. A concept analysis examining dementia caregiver resilience was conducted using Rodger's Evolutionary Method. The aim of this concept analysis was to describe the historical perspective, attributes, antecedents, and consequences of resilience as it relates to dementia caregiver mental health. Key attributes of dementia caregiver resilience were acceptance, coping strategies, social support, self-appraisal, and spirituality. The results from this concept analysis provide the foundation for the development of resilience-based interventions to support the well-being of dementia family caregivers.

Neutralization of Typhoid Toxin by Alpaca-Derived, Single-Domain Antibodies Targeting the PltB and CdtB Subunits.

Typhoid toxin is secreted by the typhoid fever-causing bacterial pathogen Salmonella enterica serovar Typhi and has tropism for immune cells and brain endothelial cells. Here, we generated a camelid single-domain antibody (VHH) library from typhoid toxoid-immunized alpacas and identified 41 VHHs selected on the glycan receptor-binding PltB and nuclease CdtB. VHHs exhibiting potent in vitro neutralizing activities from each sequence-based family were epitope binned via competition enzyme-linked immunosorbent assays (ELISAs), leading to 6 distinct VHHs, 2 anti-PltBs (T2E7 and T2G9), and 4 anti-CdtB VHHs (T4C4, T4C12, T4E5, and T4E8), whose in vivo neutralizing activities and associated toxin-neutralizing mechanisms were investigated. We found that T2E7, T2G9, and T4E5 effectively neutralized typhoid toxin in vivo, as demonstrated by 100% survival of mice administered a lethal dose of typhoid toxin and with little to no typhoid toxin-mediated upper motor function defect. Cumulatively, these results highlight the potential of the compact antibodies to neutralize typhoid toxin by targeting the glycan-binding and/or nuclease subunits.

Cognitive Intra-individual Variability in HIV: an Integrative Review.

Nearly 30-50% of people living with HIV experience HIV-Associated Neurocognitive Disorder (HAND). HAND indicates performance at least one standard deviation below the normative mean on any two cognitive domains. This method for diagnosing or classifying cognitive impairment has utility, however, cognitive intraindividual variability provides a different way to understand cognitive impairment. Cognitive intraindividual variability refers to the scatter in cognitive performance within repeated measures of the same cognitive test (i.e., inconsistency) or across different cognitive tests (i.e., dispersion). Cognitive intraindividual variability is associated with cognitive impairment and cognitive decline in various clinical populations. This integrative review of 13 articles examined two types of cognitive intraindividual variability in people living with HIV, inconsistency and dispersion. Cognitive intraindividual variability appears to be a promising approach to detect subtle cognitive impairments that are not captured by traditional mean-based neuropsychological testing. Greater intraindividual variability in people living with HIV has been associated with: 1) poorer cognitive performance and cognitive decline, 2) cortical atrophy, both gray and white matter volume, 3) poorer everyday functioning (i.e., driving simulation performance), specifically medication adherence, and 4) even mortality. This inspires future directions for research. First, greater cognitive intraindividual variability may reflect a greater task demand on executive control to harness and regulate cognitive control over time. By improving executive functioning through cognitive training, it may reduce cognitive intraindividual variability which could slow down cognitive decline. Second, cognitive intraindividual variability may be reconsidered in prior cognitive intervention studies in which only mean-based cognitive outcomes were used. It is possible that such cognitive interventions may actually improve cognitive intraindividual variability, which could have clinical relevance.

Transportation Barriers and Health-Related Quality of Life in a Sample of Middle-Aged and Older Adults Living with HIV in the Deep South.

Access to reliable transportation is a social determinant of health imperative for disease management for those aging with HIV/AIDS. To what degree transportation barriers are associated with health-related quality of life (HRQOL) in middle-aged and older people living with HIV (PWH) in the Deep South region of the United States is presently unknown. PWH (n = 261, age range = 39 to 73 years old, 80.1% African American, 64.4% male) were recruited from an academic medical center in the Deep South. Variables included sociodemographics, HIV characteristics, depressive symptoms, HRQOL, and perceived transportation barriers. Spearman rho correlations and linear regressions accounting for covariates were conducted. After accounting for covariates, greater perceived transportation barriers were associated with worse health perceptions, pain, social functioning, health distress, and health transitions. Access to reliable transportation is a key factor in improving health for PWH. Considerations for healthcare and traffic safety are discussed.

Emerging directions of cognitive aging with HIV: practice and policy implications for social work.

Cognitive impairments have been endemic to the HIV epidemic since its beginning and persist to this day. These impairments are attributed to HIV-induced neuroinflammation, the long-term effects of combination antiretroviral therapy, lifestyle factors (e.g., sedentary behavior, substance use), neuro-comorbidities (e.g., depression), age-associated comorbidities (e.g., heart disease, hypertension), and others causes. Normal aging and lifestyle also contribute to the development of cognitive impairment. Regardless of the etiology, such cognitive impairments interfere with HIV care (e.g., medication adherence) and everyday functioning (e.g., driving safely, financial management). With more than half of people with HIV (PWH) 50 years and older, and ~45% of all PWH meeting the criteria for HIV-Associated Neurocognitive Disorder (HAND), those aging PWH are more vulnerable for developing cognitive impairment. This article provides an update to a social work model to identify and monitor PWH for cognitive impairment. Within this update, the state of the science on protecting brain health and cognitive reserve within the context of neuroHIV is also presented. From this, implications for practice and policy to promote successful cognitive functioning in older PWH are provided.

Psychosocial Mechanisms of Self-rated Successful Aging with HIV: A Structural Equation Model.

This study tested a conceptual psychosocial model of self-rated successful aging (SRSA) with HIV. Our sample (n = 356) included older women living with HIV (OWLH): average age 56.5 years, 73% Black. SRSA was assessed using a research-based 10-point scale (higher scores = better outcomes). We conducted adjusted structural equation modeling. The global model included two latent variables-protective attributes (composite of positive psychosocial factors: resilience, personal mastery, optimism, spirituality) and psychological distress (composite of negative psychosocial factors: anxiety, depression, loneliness, internalized HIV-related stigma). The model showed good fit (χ2(58) = 76, p = 0.06; RMSEA = 0.03; CFI = 0.99). Increased protective attributes were associated with improved SRSA both directly and mediated by improved coping with stress. While psychological distress did not have a direct effect on SRSA, it was indirectly associated with worsened SRSA via diminished protective attributes and via decreased coping with stress. Findings suggest the need for interventions enhancing positive and mitigating negative psychosocial factors in OWLH.

Can Individualized-Targeted Computerized Cognitive Training Benefit Adults with HIV-Associated Neurocognitive Disorder? The Training on Purpose Study (TOPS).

Half of people with HIV (PWH) have HIV-associated neurocognitive disorder (HAND). This study examined whether cognition can be improved using a framework targeting impaired individual cognitive domains in PWH with HAND. In this two-group pre-post experimental design study, 88 adults with HAND were randomized to either: (1) a no-contact control group (n = 40) or (2) the Individualized-Targeted Cognitive Training group (n = 48). Baseline cognitive performance was assessed on eight cognitive domains. A theoretical framework was used to determine the two cognitive domains selected for training. With priority on speed of processing (SOP) and attention impairments, participants received SOP and/or attention training if such impairments were detected; if not, participants were assigned to cognitive training in one/two of the least impaired cognitive domains contributing to their HAND diagnosis. Global cognitive score was slightly improved following training (p = 0.256; d = - 0.21), but it was not significant. Significant improvements were observed on SOP following training in that domain (SOP; d = - 0.88; p = 0.011). SOP training also improved functioning in other cognitive domains. This individualized cognitive intervention did not change HAND status, but it did result in improved SOP, in turn yielding improvement in other cognitive domains.