RESUMO
There is wide variation in the reported prevalence of cognitive impairment in people with HIV (PWH). Part of this variation may be attributable to different studies using different methods of combining neuropsychological test scores to classify participants as either cognitively impaired or unimpaired. Our aim was to determine, in a South African cohort of PWH (N = 148), (a) how much variation in reported rates was due to method used to define cognitive impairment and (b) which method correlated best with MRI biomarkers of HIV-related brain pathology. Participants completed detailed neuropsychological assessment and underwent 3 T structural MRI and diffusion tensor imaging (DTI). We used the neuropsychological data to investigate 20 different methods of determining HIV-associated cognitive impairment. We used the neuroimaging data to obtain volumes for cortical and subcortical grey matter and total white matter and DTI metrics for several white matter tracts. Applying each of the 20 methods to the cognitive dataset resulted in a wide variation (20-97%) in estimated rates of impairment. Logistic regression models showed no method was associated with HIV-related neuroimaging abnormalities as measured by structural volumes or DTI metrics. We conclude that for the population from which this sample was drawn, much of the variation in reported rates of cognitive impairment in PWH is due to the method of classification used, and that none of these methods accurately reflects biological effects of HIV in the brain. We suggest that defining HIV-associated cognitive impairment using neuropsychological test performance only is insufficient; pre-morbid functioning, co-morbidities, cognitive symptoms, and functional impairment should always be considered.
Assuntos
Complexo AIDS Demência/classificação , Complexo AIDS Demência/diagnóstico , Adulto , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Neuroimagem , África do SulRESUMO
Most studies that have examined neuropsychological impairments associated with human immunodeficiency virus (HIV) have focused on males, yet females represent one of the largest groups of newly infected patients. Further, few studies have examined neuropsychological performance and neuroimaging outcomes among females compared to males in the modern era of highly active anti-retroviral therapy (HAART). The present study investigated neuropsychological performance and brain volumetrics among HIV+ males (n = 93) and females (n = 44) on stable HAART compared to HIV seronegative (HIV-) males (n = 42) and females (n = 49). Results revealed a significant effect of HIV on neuropsychological performance and neuroimaging measures. An effect of gender, independent of HIV status, was also observed for neuroimaging measures but not neuropsychological performance. Additionally, no significant differences in neuropsychological performance or brain volumetrics were seen between HIV+ males and females. No significant interaction was observed between HIV and gender on either neuropsychological or neuroimaging indices. Our results suggest that both HIV+ males and females treated with HAART experience similar outcomes in terms of brain integrity.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Encéfalo/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Infecções por HIV/fisiopatologia , RNA Viral/sangue , Idoso , Terapia Antirretroviral de Alta Atividade , Encéfalo/virologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Estudos de Casos e Controles , Transtornos Cognitivos/complicações , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/virologia , Feminino , Neuroimagem Funcional , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , RNA Viral/antagonistas & inibidores , Carga Viral/efeitos dos fármacosRESUMO
INTRODUCTION: Following a nonfatal opioid overdose, patients are at high risk for repeat overdose. The objective of this study was to examine the association of MOUD after nonfatal opioid overdose with risk of repeat overdose in the following year. METHODS: This retrospective cohort study analyzed Missouri Medicaid claims from July 2012 to December 2021. The study identified opioid overdoses occurring between 2013 and 2020 using diagnosis codes for opioid poisoning in an inpatient or emergency department setting. The study implemented Cox models with a time-varying covariate for post-overdose receipt of MOUD. RESULTS: During the study period, MOUD receipt after overdose more than tripled, from 4.8 % to 18.9 %. Overall, only 12.1 % of patients received MOUD in the year after index. MOUD during follow-up was associated with significantly lower risk of repeat overdose (HR = 0.34, 95 % CI = 0.14-0.82). Out of 3017 individuals meeting inclusion criteria, 13.6 % had a repeat opioid overdose within 1 year. Repeat overdose risk was higher for those whose index overdose involved heroin or synthetic opioids (HR = 1.71, 95 % CI = 1.35-2.15), but MOUD was associated with significantly reduced risk in this group (HR = 0.34, 95 % CI = 0.13-0.92). CONCLUSIONS: MOUD receipt was associated with reduced risk of repeat overdose. Those whose index overdoses involved heroin or synthetic opioids were at greater risk of repeat overdose, but MOUD was associated with reduced risk in this group.
Assuntos
Overdose de Drogas , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Estados Unidos/epidemiologia , Humanos , Estudos de Coortes , Overdose de Opiáceos/epidemiologia , Medicaid , Heroína/uso terapêutico , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Analgésicos Opioides/efeitos adversos , Overdose de Drogas/epidemiologiaRESUMO
Importance: Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective: To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants: This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures: Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results: After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] ß = 16.66 [4.72] mm3 per 100 cells/mm3; P < .001) and thalamic (mean [SE] ß = 32.24 [8.96] mm3 per 100 cells/mm3; P < .001) volumes and larger ventricles (mean [SE] ß = -391.50 [122.58] mm3 per 100 cells/mm3; P = .001); in participants not taking cART, however, lower current CD4+ cell counts were associated with smaller putamen volumes (mean [SE] ß = 57.34 [18.78] mm3 per 100 cells/mm3; P = .003). A dVL was associated with smaller hippocampal volumes (d = -0.17; P = .005); in participants taking cART, dVL was also associated with smaller amygdala volumes (d = -0.23; P = .004). Conclusions and Relevance: In a large-scale international population of HIV-positive individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Our findings extend beyond the classically implicated regions of the basal ganglia and may represent a generalizable brain signature of HIV infection in the cART era.
Assuntos
Encéfalo/patologia , Contagem de Linfócito CD4 , Infecções por HIV , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Little is known about the contribution of white matter integrity to inhibitory cognitive control, particularly in healthy aging. The present study examines the correspondence between white matter fiber bundle length and behavioral inhibition in 37 community-dwelling older adults (aged 51-78 years). Participants underwent neuroimaging with 3 Tesla MRI, and completed a behavioral test of inhibition (i.e., Go/NoGo task). Quantitative tractography derived from diffusion tensor imaging (qtDTI) was used to measure white matter fiber bundle lengths (FBLs) in tracts known to innervate frontal brain regions, including the anterior corpus callosum (AntCC), the cingulate gyrus segment of the cingulum bundle (CING), uncinate fasciculus (UNC), and the superior longitudinal fasciculus (SLF). Performance on the Go/NoGo task was measured by the number of commission errors standardized to reaction time. Hierarchical regression models revealed that shorter FBLs in the CING (p < 0.05) and the bilateral UNC (p < 0.01) were associated with lower inhibitory performance after adjusting for multiple comparisons, supporting a disconnection model of response inhibition in older adults. Prospective longitudinal studies are needed to examine the evolution of inhibitory errors in older adult populations and potential for therapeutic intervention.
Assuntos
Envelhecimento Saudável , Inibição Psicológica , Fibras Nervosas Mielinizadas , Substância Branca , Idoso , Encéfalo/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais , Testes Neuropsicológicos , Tempo de Reação , Análise e Desempenho de Tarefas , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagemRESUMO
This study examines white matter microstructure using quantitative tractography diffusion magnetic resonance imaging (qtdMRI) in HIV+ individuals from South Africa who were naïve or early in the initiation of antiretroviral therapy. Fiber bundle length (FBL) metrics, generated from qtdMRI, for whole brain and six white matter tracts of interest (TOI) were assessed for 135 HIV+ and 21 HIV- individuals. The association between FBL metrics, measures of disease burden, and neuropsychological performance were also investigated. Results indicate significantly reduced sum of whole brain fiber bundle lengths (FBL, p < 0.001), but not average whole brain FBL in the HIV+ group compared to the HIV- controls. The HIV+ group exhibited significantly shorter sum of FBL in all six TOIs examined: the anterior thalamic radiation, cingulum bundle, inferior and superior longitudinal fasciculi, inferior frontal occipital fasciculus, and the uncinate fasciculus. Additionally, average FBLs were significantly shorter select TOIs including the inferior longitudinal fasciculus, cingulum bundle, and the anterior thalamic radiation. Shorter whole brain FBL sum metrics were associated with poorer neuropsychological performance, but were not associated with markers of disease burden. Taken together these findings suggest HIV affects white matter architecture primarily through reductions in white matter fiber numbers and, to a lesser degree, the shortening of fibers along a bundle path.
Assuntos
Imagem de Tensor de Difusão , Infecções por HIV/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Feminino , Infecções por HIV/patologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Tamanho do Órgão , África do Sul , Substância Branca/patologia , Adulto JovemRESUMO
Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV- controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T1-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV- controls (p < 0.05). GDSs and performance on learning/recall tasks were negatively correlated with the clustering coefficient (p < 0.05) in HIV+ participants. Results from this study indicate disruption to brain network integrity in treatment-limited HIV+ young adults with corresponding abnormalities in cognitive performance.
Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Infecções por HIV/patologia , Vias Neurais/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Análise de Variância , Linfócitos T CD4-Positivos/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/patologia , Vias Neurais/virologia , Testes Neuropsicológicos , Substância Branca/virologia , Adulto JovemRESUMO
Recent work using novel neuroimaging methods has revealed shorter white matter fiber bundle length (FBL) in older compared to younger adults. Shorter FBL also corresponds to poorer performance on cognitive measures sensitive to advanced age. However, it is unclear if individual factors such as cognitive reserve (CR) effectively moderate the relationship between FBL and cognitive performance. This study examined CR as a potential moderator of cognitive performance and brain integrity as defined by FBL. Sixty-three healthy adults underwent neuropsychological evaluation and 3T brain magnetic resonance imaging. Cognitive performance was measured using the Repeatable Battery of Assessment of Neuropsychological Status (RBANS). FBL was quantified from tractography tracings of white matter fiber bundles, derived from the diffusion tensor imaging. CR was determined by estimated premorbid IQ. Analyses revealed that lower scores on the RBANS were associated with shorter whole brain FBL (p = 0.04) and lower CR (p = 0.01) CR moderated the relationship between whole brain FBL and RBANS score (p < 0.01). Tract-specific analyses revealed that CR also moderated the association between FBL in the hippocampal segment of the cingulum and RBANS performance (p = 0.03). These results demonstrate that lower cognitive performance on the RBANS is more common with low CR and short FBL. On the contrary, when individuals have high CR, the relationship between FBL and cognitive performance is attenuated. Overall, CR protects older adults against lower cognitive performance despite age-associated reductions in FBL.
Assuntos
Encéfalo/patologia , Reserva Cognitiva , Envelhecimento Saudável/patologia , Envelhecimento Saudável/psicologia , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Inteligência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fibras Nervosas Mielinizadas/patologia , Testes Neuropsicológicos , Análise de Regressão , Fatores Sexuais , Substância Branca/diagnóstico por imagemRESUMO
The incidence of HIV-associated dementia has been greatly reduced in the era of highly active antiretroviral therapy (HAART); however milder forms of cognitive impairment persist. It remains uncertain whether HAART regimens with a high degree of central nervous system penetration effectiveness (CPE) exert beneficial neurological outcomes in HIV-infected (HIV+) individuals on stable treatment. Sixty-four HIV-infected adults on HAART were assigned a CPE score using a published ranking system and divided into high (≥7; n = 35) and low (<7; n = 29) CPE groups. All participants completed neuropsychological testing in addition to structural neuroimaging. Neuropsychological tests included measures known to be sensitive to HIV with values converted into standardized scores (NPZ-4) based on published normative scores. A semi-automated methodology was utilized to assess brain volumetrics within cortical (grey and white matter) and subcortical (thalamus, caudate, putamen) regions of interest. Analyses assessed NPZ-4 and brain volumetric differences between HIV+ individuals with high and low CPE scores. No significant differences in brain integrity were observed between the two groups. Long-term HAART regimens with a high degree of CPE were not associated with significantly improved neuropsychological or neuroimaging outcomes in HIV+ adults. Results suggest that alternate mechanisms may potentially contribute to better neurological outcomes in the era of HAART.