Apathy in persons living with HIV disease: A systematic narrative review.

BACKGROUND: Apathy was identified as a feature of HIV early in the epidemic; however, there are no systematic reviews of the diverse literature on the sociodemographic and clinical correlates of apathy in HIV disease. METHODS: The current study adopted a hybrid systematic-narrative review methodology in which we used PRISMA guidelines to identify, summarize, and critique peer-reviewed, empirical studies of apathy in HIV disease in the era of combination antiretroviral therapy. RESULTS: A total of 34 studies of apathy in persons living with HIV (PLWH) were identified. Findings across these studies showed that apathy was reliably related to the structure of grey and white matter pathways commonly implicated in apathy, poorer everyday functioning, education, and other neuropsychiatric symptoms (e.g., depression). Apathy was not reliably associated with age, sex, race/ethnicity, cognition, and clinical markers of HIV disease. LIMITATIONS: The current review does not provide rigorous quantitative estimates of clinical correlates of apathy, and the exclusion criteria of non-English and non-peer reviewed publications introduces risk of bias and Type I error. CONCLUSIONS: Apathy occurs at higher rates in PLWH and is linked to neuroanatomical differences, as well as negative outcomes for everyday functions, aspects of neurocognition, and neuropsychiatric symptoms. As such, apathy is an important component to consider in the clinical assessment, diagnosis, and management of neurocognitive disorders in PLWH. Future work is needed to replicate existing findings with larger sample sizes and longitudinal designs, examine apathy as a multi-dimensional construct, and develop evidence-based treatments for apathy in PLWH.

The Relationship Between Apathy and Cognitive Impairment Among Hispanic/Latin Americans: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses Systematic Review.

OBJECTIVES: The primary aim was to evaluate apathy assessment measures in relation to cognitive impairment among Hispanic/Latin Americans. METHODS: A systematic review on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and using APA PsycInfo, Embase, and PubMed databases. Inclusion criteria required (1) a sample of English or Spanish-speaking adults ages 18 years and older, (2) with measures of apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with at least 18.5% Hispanic/Latin American represented in the sample. RESULTS: Only 14 papers met criteria to be included in this review. Of the 12 cross-sectional studies, 9 demonstrated significant associations between increased apathy and cognitive impairment, 1 demonstrated a descriptive difference between apathy and cognitive status (ie, no hypothesis test conducted), while 2 demonstrated null effects. These cross-sectional studies consisted of community and clinic samples of participants across North and South America. Two longitudinal studies conducted in North America demonstrated non-significant associations of apathy with cognitive status. CONCLUSIONS: The Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) apathy subscales were the most used measures for apathy in this review (85.7% of included studies). However, validity evidence from a review of apathy measures has warranted caution against the use of the NPI outside the context of screening for apathy. This potential measurement bias with Hispanic/Latin Americans apathy research limits conclusions drawn from the present review.

Multiple Chronic Conditions and Disability among Vietnamese Older Adults: Results from the Vietnamese Aging and Care Survey (VACS).

Using data from Vietnamese-origin older immigrants/refugees in the Houston, Texas area, we assessed their overall health, chronic conditions, disability, depressive symptoms, and cognitive impairment, and examined the association between their chronic conditions and disability by comorbidity clusters. The mean age of the sample was 76 years old. The majority were married in fair/poor health with several chronic conditions and disabilities and lived with families in low-income households. Hypertension and arthritis were the most common health conditions, but cognitive impairment had the most significant impact on their disability. They experienced similar health conditions to other older Americans but had higher rates of depressive symptoms and cognitive impairment possibly due to cultural factors that may have delayed mental health treatment. Culturally and linguistically tailored services created by policymakers, healthcare professionals, and local social service agencies are recommended for the well-being of immigrants/refugees who migrated to the U.S. for a better life.

Evidence for the reliability and validity of a Spanish translation of the Medication Management Ability Assessment administered via tele-assessment.

We translated the Medication Management Ability Assessment (MMAA) from English to Spanish for use via tele-assessment and examined its reliability and validity. Following International Test Commission Guidelines for Translating and Adapting Tests, we used translation/back-translation and a small focus group (n = 6) to adapt a Spanish version of the MMAA. Eighty-six Spanish-speaking adults completed the adapted MMAA via tele-assessment at baseline and at a two-week follow-up visit. Participants also completed several self-report and performance-based cognitive and functional measures. The internal consistency of the MMAA was excellent (standardized Cronbach's α = 0.90). Performance-based functional assessments (PBFAs) and objective cognition were positively associated with the MMAA at small to medium effect sizes. Self-report measures of daily function and cognition, measures of health literacy, and estimates of premorbid intellectual functioning were not significantly associated with MMAA performance. The test-retest reliability of the MMAA was good (CCC = 0.73, 95% CI [0.62, 0.81]; rs = 0.37, p < 0.001) and demonstrated a small practice effect (Cohen's d = 0.36, p = 0.001). Preliminary evidence for the construct validity of a Spanish-language MMAA administered via tele-assessment further expands the potential clinical utility of PBFAs in culturally diverse, Spanish-speaking populations.

Self-report depression screening measures for older Hispanic/Latin American adults: A PRISMA systematic review.

BACKGROUND: Assessing depression symptoms in Hispanic/Latin American (H/Ls) older adults, a group at high risk for depression, is nuanced due to the influence of cultural characteristics in symptom expression and manifestation. Little is known about the psychometric properties of available measures when used with this population. METHODS: We conducted a two-stage systematic review of available depression assessment tools. We first identified self-report measures designed for use with adults. We then identified studies where at least one of such measures was used with older H/Ls that reported psychometric properties for the measure(s) used. RESULTS: Only 3 measures were identified for use with older H/Ls: the BDI, GDS, and CES-D. However, few data were found to support the validity of the BDI, and the CES-D was not consistently valid across cultural groups. The GDS was found appropriate, though its performance varied based on race/ethnicity, nationality, and cutoff scores. The CES-D and GDS also demonstrated varying psychometric properties based on study setting (research versus clinical) and target population (inpatient psychiatric patients versus community-dwelling individuals). LIMITATIONS: The number of articles that met criteria for inclusion in our review was small, and there was variation among samples of the few studies included. CONCLUSIONS: Currently available self-report depression screening measures have acceptable applicability among older H/Ls, but their utility may vary based on their intended use. Modified cutoff scores may be beneficial in maximizing the utility of these measures when given to diverse older adults.

Differential item functioning of the Beck Anxiety Inventory in a rural, multi-ethnic cohort.

BACKGROUND: Evaluating measurement bias is vital to ensure equivalent assessment across diverse groups. One approach for evaluating test bias, differential item functioning (DIF), assesses item-level bias across specified groups by comparing item-level responses between groups that have the same overall score. Previous DIF studies of the Beck Anxiety Inventory (BAI) have only assessed bias across age, sex, and disease duration in monolingual samples. We expand this literature through DIF analysis of the BAI across age, sex, education, ethnicity, cognitive status, and test language. METHODS: BAI data from a sample (n = 527, mean age=61.4 ± 12.7, mean education=10.9 ± 4.3, 69.3% female, 41.9% Hispanic/Latin American) from rural communities in West Texas, USA were analyzed. Item response theory (IRT) / logistic ordinal regression DIF was conducted across dichotomized demographic grouping factors. The Mann-Whitney U test and Hedge's g standardized mean differences were calculated before and after adjusting for the impact of DIF. RESULTS: Significant DIF was demonstrated in 10/21 items. An adverse impact of DIF was not identified when demographics were assessed individually. Adverse DIF was identified for only one participant (1/527, 0.2%) when all demographics were aggregated. LIMITATIONS: These results might not be generalizable to a sample with broader racial representation, more severe cognitive impairment, and higher levels of anxiety. CONCLUSIONS: Minimal item-level bias was identified across demographic factors considered. These results support prior evidence that the BAI is valid for assessing anxiety across age and sex while contributing new evidence of its clinical relevance across education, ethnicity, cognitive status, and English/Spanish test language.

Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure.

In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (H2S), and increased H2S activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent H2S synthesis augments vascular resistance in control rats. The goal of this study was to evaluate the contribution of IH-induced changes in CSE signaling to increased blood pressure and vascular resistance. We hypothesized that chronic IH exposure eliminates CSE regulation of blood pressure (BP) and vascular resistance. In rats instrumented with venous catheters, arterial telemeters, and flow probes on the main mesenteric artery, the CSE inhibitor dl-propargylglycine (PAG, 50 mg/kg/day i.v. for 5 days) increased BP in Sham rats but decreased BP in IH rats [in mmHg, Sham (n = 11): 114 ± 4 to 131 ± 6; IH (n = 8): 131 ± 8 to 115 ± 7 mmHg, P < 0.05]. PAG treatment increased mesenteric vascular resistance in Sham rats but decreased it in IH rats (day 5/day 1: Sham: 1.50 ± 0.07; IH: 0.85 ± 0.19, P < 0.05). Administration of the ganglionic blocker hexamethonium (to evaluate SNS activity) decreased mesenteric resistance in PAG-treated Sham rats more than in saline-treated Sham rats or PAG-treated IH rats. CSE immunoreactivity in IH carotid bodies compared with those from Sham rats. However, CSE staining in small mesenteric arteries was less in arteries from IH than in Sham rats but not different in larger arteries (inner diameter > 200 µm). These results suggest endogenous H2S regulates blood pressure and vascular resistance, but this control is lost after IH exposure with decreased CSE expression in resistance size arteries. IH exposure concurrently increases carotid body CSE expression and relative SNS control of blood pressure, suggesting both vascular and carotid body H2S generation contribute to blood pressure regulation.NEW & NOTEWORTHY These results suggest that CSE's protective role in the vasculature is impaired by simulated sleep apnea, which also upregulates CSE in the carotid body. Thus, this enzyme system can exert both pro- and antihypertensive effects and may contribute to elevated SNS outflow in sleep apnea.

Hydrogen sulfide regulation of renal and mesenteric blood flow.

Hydrogen sulfide (H2S) dilates isolated arteries, and knockout of the H2S-synthesizing enzyme cystathionine γ-lyase (CSE) increases blood pressure. However, the contributions of endogenously produced H2S to blood flow regulation in specific vascular beds are unknown. Published studies in isolated arteries show that CSE production of H2S influences vascular tone more in small mesenteric arteries than in renal arteries or the aorta. Therefore, the goal of this study was to evaluate H2S regulation of blood pressure, vascular resistance, and regional blood flows using chronically instrumented rats. We hypothesized that during whole animal CSE inhibition, vascular resistance would increase more in the mesenteric than the renal circulation. Under anesthesia, CSE inhibition [ß-cyanoalanine (BCA), 30 mg/kg bolus + 5 mg·kg-1·min-1 for 20 min iv) rapidly increased mean arterial pressure (MAP) more than saline administration (%Δ: saline -1.4 ± 0.75 vs. BCA 7.1 ± 1.69, P < 0.05) but did not change resistance (MAP/flow) in either the mesenteric or renal circulation. In conscious rats, BCA infusion similarly increased MAP (%Δ: saline -0.8 ± 1.18 vs. BCA 8.2 ± 2.6, P < 0.05, n = 7) and significantly increased mesenteric resistance (saline 0.9 ± 3.1 vs. BCA 15.6 ± 6.5, P < 0.05, n = 12). The H2S donor Na2S (50 mg/kg) decreased blood pressure and mesenteric resistance ,but the fall in resistance was not significant. Inhibiting CSE for multiple days with dl-proparglycine (PAG, 50 mg·kg-1·min-1 iv bolus for 5 days) significantly increased vascular resistance in both mesenteric (ratio of day 1: saline 0.86 ± 0.033 vs. PAG 1.79 ± 0.38) and renal circulations (ratio of day 1: saline 1.26 ± 0.22 vs. 1.98 ± 0.14 PAG). These results support our hypothesis that CSE-derived H2S is an important regulator of blood pressure and vascular resistance in both mesenteric and renal circulations. Furthermore, inhalation anesthesia diminishes the effect of CSE inhibition on vascular tone.NEW & NOTEWORTHY These results suggest that CSE-derived H2S has a prominent role in regulating blood pressure and blood flow under physiological conditions, which may have been underestimated in prior studies in anesthetized subjects. Therefore, enhancing substrate availability or enzyme activity or dosing with H2S donors could be a novel therapeutic approach to treat cardiovascular diseases.

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage.

Non-traumatic subarachnoid hemorrhage (SAH) affects an estimated 30,000 people each year in the United States, with an overall mortality of ~30%. Most cases of SAH result from a ruptured intracranial aneurysm, require long hospital stays, and result in significant disability and high fatality. Early brain injury (EBI) and delayed cerebral vasospasm (CV) have been implicated as leading causes of morbidity and mortality in these patients, necessitating intense focus on developing preclinical animal models that replicate clinical SAH complete with delayed CV. Despite the variety of animal models currently available, translation of findings from rodent models to clinical trials has proven especially difficult. While the explanation for this lack of translation is unclear, possibilities include the lack of standardized practices and poor replication of human pathophysiology, such as delayed cerebral vasospasm and ischemia, in rodent models of SAH. In this review, we summarize the different approaches to simulating SAH in rodents, in particular elucidating the key pathophysiology of the various methods and models. Ultimately, we suggest the development of standardized model of rodent SAH that better replicates human pathophysiology for moving forward with translational research.

Role of Interleukin-10 in Acute Brain Injuries.

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation.