We used Bonferroni corrections for multiple comparisons with alpha set at 0.008 for each comparison of two TES components. We used continuous and not dichotomous versions of our trauma, SES, and stress variables in post-hoc analyses to more precisely examine the contribution of each variable by utilizing the full range of variability in each of the scores. We also examined how the individual components of TES related to the cognitive and functional outcomes in PLWH using Cohen’s d for dichotomous variables , Pearson’s correlations forcontinuous variables approximating a normal distribution , and Spearman’s rho correlations for non-normally distributed continuous variables . To adjust for multiple comparisons, alpha was set based on the number of outcomes for each TES component: 0.013 . In PLWH, elevated composite TES scores related to worse executive function, learning, and working memory performance, as well as worse daily functional abilities. The impact of these common traumatic and stressful experiences in PLWH may help to explain the high rates of mild neurocognitive and functional impairment observed in this population. When individual components of TES were examined, food insecurity and stress were closely related to ADL declines,best way to dry cannabis while TES components had overall small and non-significant relationships with cognitive domains of executive function, learning, and working memory.
While mechanisms underlying the associations among TES and cognitive and everyday functioning are unclear, one possibility for the relation with lower cognitive and everyday functioning among PLWH is the combined effects of multiple adverse experiences and HIV on chronic immune dysregulation and inflammation. Based on our findings, we cannot definitively state that the TES-cognition relationship differs between the HIV+ and HIV- groups because we only observed additive main effects of HIV and TES and not an interaction on global cognition in our whole sample model. However, our HIV-stratified results suggest an interaction given that we saw a significant relationship between TES and domain-specific cognitive performance in the HIV+ group but not in the HIV- group. Given the lower rates of trauma, food insecurity, stress, and less low SES in the HIV- group, we have a limited ability to assess the relation between these adverse experiences and cognitive and functional outcomes in those without HIV. Our findings suggest that TES is especially deleterious for cognitive and everyday functioning among PLWH given that TES remained a significant predictor even when controlling for demographic, educational, substance use, psychiatric, and HIV disease characteristics. Our post-hoc analyses revealed that, among PLWH, the individual components of our TES composite had small correlations with each other, indicating that trauma, economic hardship, and stress captured distinct but overlapping experiences.
Furthermore, our post-hoc analyses showed that the correlations between the individual components of our TES composite and our outcome variables ranged broadly from small to moderate, suggesting that our findings are driven by the combination of these variables acting cumulatively to negatively impact everyday cognition and functional independence. Our results, which found that elevated TES composite scores are related to difficulties in executive functioning, learning, and working memory, are consistent with previous research that identified executive functioning and learning/memory domains as predominant areas of cognitive deficit in HIV . Given these findings, it is possible that trauma, economic hardship, and stress contribute to the worse neurocognitive functioning and the presence of mild neurocognitive impairment in HIV, which is prevalent in about 45% of PLWH. In addition, our study confirms and extends previous research, which found a relationship between stressful life events and neuropsychological performance in men living with HIV, but not in men without HIV . Not only did we confirm this relationship, but we found that other socioenvironmental factors, such as economic hardship, significantly influence this relationship in a sample of men and women living with HIV. These findings have clear clinical utility for PLWH’s overall healthcare. Specifically, these findings point toward screenings for adverse experiences. These screenings may allow for directed, comprehensive, services and resources, provided with cultural humility, that address social and structural factors. Such screenings and services may help to break the cycle of exposure to chronically stressful and traumatic contexts that may play a role in cognitive and functional impairment.
Adversity assessments may also help to identify those who require additional screening for HIV-associated cognitive impairment. Our sample of participants without HIV reported a limited amount of trauma, economic hardship, and stress, which contributed to a restricted TES composite range. This restricted range may have contributed to the lack of relationship observed between our predictors and outcomes in this group. Thus, we have limited evidence to claim that trauma, economic hardship, and stress are unrelated to cognition and everyday functioning in individuals without HIV. There were a number of strengths in our study. First, we were able to identify significant effects of trauma, economic hardship, and stress on three cognitive domains and everyday functioning in a medium-sized sample of PLWH and compare these effects to those seen in a HIV- group. Second, our study utilized a comprehensive neuropsychological battery to assess cognitive functioning, which used multiple tests to tap seven domains of cognition. Finally, our study controlled for many more traditional predictors of cognitive and functional outcomes in PLWH than previous studies. Even when controlling for these covariates, results remained significant, demonstrating a unique and important contribution of adversity to these outcomes in PLWH. Our study also had several limitations. By nature, the cross-sectional design precludes detection of casual inference from the observed relationship of trauma, economic hardship, and stress with neurocognitive and everyday functioning in HIV. We also cannot rule out the possibility of causality in the opposite direction, such that worse neurocognitive and everyday function contribute to risk for trauma, economic hardship, and stress. Longitudinal studies, which are planned, are necessary to expand our understanding and explore the direction of effects between these factors. Our measures of trauma, stress, and economic hardship, were temporally limited to assessment of recent traumatic events , recent perceived stress , SES , and food insecurity , and did not capture cumulative stressors over the lifetime. With these time-frame constraints, our study lacked indicators of early life stress such as childhood trauma, which has been shown to have an interactive effect with HIV on neuropsychological functioning and structural morphology of the brain . Our trauma scale consisted of five items from the WHI Life Events Scale and has not been psychometrically validated as a measure of traumatic events. To better capture trauma, the 10-item Brief Trauma Questionnaire , which assesses type and severity of traumatic event and the 20-item PTSD Checklist for DSM-5 , which captures severity of PTSD symptoms, should be employed in future studies. Moreover, our study did not assess experiences of stigma and discrimination, a form of adversity that can act as a psychosocial stressor . Many PLWH experience discrimination due to their HIV or AIDS status, and/or the intersection of other identities such as sexual orientation, race/ethnicity, gender identity, and/or socioeconomic position,how to cure cannabis and these common experiences relate to worse health outcomes To the best of our knowledge this is the first study to examine the combined relationship of adverse social, structural, and psychological factors such as trauma, economic hardship, and stress concurrently with HIV on neurocognitive and everyday functioning outcomes. Given that there are high rates of sexual and physical abuse, trauma, and poverty among those living with HIV, the impact of these acute and chronic experiences should be a research priority with high clinical relevance, particularly in a population that often experiences compromised neurocognitive and immunological functioning.
Clinically, assessing and addressing traumatic, stressful, and other adverse events in holistic and culturally-informed ways should be a part of standard HIV care. Future research should investigate the impact of trauma, economic hardship, and stress on the confluence of inflammation, immune dysregulation, and associated neural alterations in PLWH. In particular, examination of biomarkers of stress and trauma in PLWH may help to understand mechanisms underlying the associations between TES and neurocognitive and everyday function observed in this study. Efforts to reduce trauma, poverty, and other stressful contexts and developing resources to help people manage and cope with past and current adverse circumstances could be relevant to decreasing neurocognitive impairment, particularly the high rates of mild neurocognitive disorder, in PLWH. The Human Immunodeficiency Virus enters the central nervous system within days of initial infection , in many cases leading to neurological, cognitive, and behavioral complications. Cognitive deficits are a common feature of HIV/AIDS. While the incidence of HIV-associated dementia has considerably decreased in the era of modern ART suppressing viral replication, mild cognitive deficits with no change in everyday function persist in 24% [95% confidence interval = 20.3–26.8] of people with HIV and mild cognitive deficits with mildly decreased everyday function persist in about 13.3% of PWH . Although executive function and memory deficits are most common in PWH in the post-ART era, the characterization of cognitive impairment in HIV is highly variable with deficits observed in a range of cognitive domains . Previous studies using statistical clustering techniques have identified differing profiles of cognitive function among PWH with some profiles resembling global impairment across domains while other profiles resemble more domain-specific impairment, particularly in the domains of episodic memory and executive function . Similarly, there is also substantial variability in the risk factors associated with cognitive deficits among PWH that range from biological , demographic to psychosocial factors . The persistence of cognitive impairment in the era of modern ART among PWH and the variability in the profiles and risk factors associated with cognitive impairment suggests that non-HIV factors associated with aging, comorbid conditions and psychosocial risk factors likely contribute to cognitive impairment given the high prevalence of these factors among PWH . With this in mind, we propose looking beyond the construct of HIV-associated neurocognitive disorders to identify the underlying pathophysiology linked to cognitive impairment as HAND requires other comorbidities to be ruled out as primary contributing factors. Biological sex is an important determinant of cognitive impairment among PWH. In a recent literature review of sex differences in cognitive impairment among PWH , seven cross-sectional and one longitudinal analysis identified sex differences on global measures of cognitive impairment among PWH. Additionally, six cross-sectional and one longitudinal analysis also reported sex differences in domain-specific cognitive performance. The strongest available evidence of adequately-powered studies indicates that WWH show greater deficits than MWH in the domains of learning and memory followed by speed of information processing and motor functioning, with inconsistent findings in executive functioning . The greater vulnerability of WWH to cognitive impairment may reflect sociodemographic differences between men and women with HIV. WWH tend to have a higher prevalence of psychosocial risk factors including poverty, low literacy levels, low educational attainment, substance abuse, poor mental health, and barriers to health care services as compared to MWH. These psychosocial risk factors may have biological effects on the brain that lead to reduced cognitive reserve among WWH as evidenced by findings of greater susceptibility of cognitive function to the effects of mental health factors among WWH vs. MWH . Additionally, biological factors such as sex steroid hormones and female-specific hormonal milieus may contribute to sex differences in cognitive test performance in PWH. However, it remains unclear how MWH and WWH may differ in the patterns of cognitive impairment and risk factors associated with these patterns of cognitive impairment. Previous reports of impairment profiles among PWH have identified them in combined samples of men and women , masking possible sex-specific patterns of cognitive impairment among PWH. Furthermore, although a number of studies reported sex differences in the presence and pattern of cognitive impairment and greater cognitive decline compared to MWH , only one study was adequately powered to address meaningful sex difference in global cognitive function . A well-powered examination of the patterns and determinants of cognitive impairment by sex, that also controls for other demographic differences between WWH and MWH , can help to clarify the contribution of sex to heterogeneity in cognitive impairment among PWH. Such an examination could also clarify the related psychosocial vs. biological factors and, thereby, optimize risk assessments and intervention strategies in both sexes.