RESUMO
The expression of cognitive symptoms associated with HIV varies over time and across individuals. This pattern may reflect transient contextual factors, including the degree of effort exerted by individuals undergoing cognitive testing. The present study examined whether effort corresponds to the expression of persistent HIV-related cognitive impairment among individuals receiving combination antiretroviral therapy (cART). HIV+ individuals (n = 111) averaged 48.2 (14.9) years of age and 13.0 (2.7) years of education and HIV- individuals (n = 92) averaged 34.9 (17.2) years of age and 13.5 (1.9) years of education. Participants completed a neuropsychological battery and a clinically validated measure of effort (Test of Memory Malingering, trial 1). Results revealed that the vast majority of HIV+ (85%) and HIV- (89%) individuals performed above published guidelines for adequate effort. Furthermore, the expression of cognitive impairment in HIV was not related to effort performance. The results were unchanged when examining HIV+ individuals with and without viral suppression. Finally, disability and disability-seeking status, and a proxy measure of apathy did not correspond to effort levels in HIV+ individuals. These findings suggest that variability in the expression of cognitive impairment in the cART era is unlikely to represent overt effort failures or other confounds unrelated to the disease. Persistent cognitive impairment in HIV likely represents historical and/or ongoing disease mechanisms despite otherwise successful treatment.
Assuntos
Complexo AIDS Demência/diagnóstico , Simulação de Doença/psicologia , Motivação , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/psicologia , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.
Assuntos
Substituição de Aminoácidos , Imagem de Tensor de Difusão/métodos , Infecções por HIV/diagnóstico por imagem , HIV/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/patologia , Núcleo Caudado/virologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Corpo Caloso/virologia , Imagem de Tensor de Difusão/instrumentação , Feminino , Expressão Gênica , Variação Genética , Genótipo , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/virologia , HIV/patogenicidade , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Putamen/diagnóstico por imagem , Putamen/patologia , Putamen/virologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Tálamo/virologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/virologiaRESUMO
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
Variations of the cholesteryl ester transfer protein polymorphism (CETP I405V/rs5882) have been associated with an increased risk for neurodegeneration, particularly when examined in conjunction with the epsilon 4 isoform of apolipoprotein E (ApoE4). Despite these identified relationships, the impact of I405V on gray matter microstructure remains unknown. The present study examined the impact of the CETP I405V polymorphism on gray matter integrity among 52 healthy adults between ages 51 and 85. Gray matter was measured bilaterally using diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Participants were grouped according to a dominant statistical model (II genotype vs. IV/VV genotypes) and secondary analyses were completed to examine the interactive effects of CETP and ApoE4 on DTI metrics. Compared to individuals with the IV/VV genotypes, II homozygotes demonstrated significantly higher MD in bilateral temporal, parietal, and occipital gray matter. Secondary analyses revealed higher FA and AD in the left temporal lobe of IV/VV genotypes with an ApoE4 allele. Our results provide preliminary evidence that CETP II homozygosity is a predisposing risk factor for gray matter abnormalities in posterior brain regions in healthy older adults, independent of an ApoE4 allele.
Assuntos
Transporte Biológico/genética , Encéfalo/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/genética , Colesterol/metabolismo , Substância Cinzenta/metabolismo , Polimorfismo Genético , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Apolipoproteínas E/genética , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Genótipo , Técnicas de Genotipagem , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Modelos EstatísticosRESUMO
Prior research has suggested benefits of aerobic physical activity (PA) on cognition and brain volumes in HIV uninfected (HIV-) individuals, however, few studies have explored the relationships between PA and brain integrity (cognition and structural brain volumes) in HIV-infected (HIV+) individuals. Seventy HIV+ individuals underwent neuropsychological testing, structural neuroimaging, laboratory tests, and completed a PA questionnaire, recalling participation in walking, running, and jogging activities over the last year. A PA engagement score of weekly metabolic equivalent (MET) hr of activity was calculated using a compendium of PAs. HIV+ individuals were classified as physically active (any energy expended above resting expenditure, n=22) or sedentary (n=48). Comparisons of neuropsychological performance, grouped by executive and motor domains, and brain volumes were completed between groups. Physically active and sedentary HIV+ individuals had similar demographic and laboratory values, but the active group had higher education (14.0 vs. 12.6 years, p=.034). Physically active HIV+ individuals performed better on executive (p=.040, unadjusted; p=.043, adjusted) but not motor function (p=.17). In addition, among the physically active group the amount of physical activity (METs) positively correlated with executive (Pearson's r=0.45, p=0.035) but not motor (r=0.21; p=.35) performance. In adjusted analyses the physically active HIV+ individuals had larger putamen volumes (p=.019). A positive relationship exists between PA and brain integrity in HIV+ individuals. Results from the present study emphasize the importance to conduct longitudinal interventional investigation to determine if PA improves brain integrity in HIV+ individuals.
Assuntos
Encéfalo/patologia , Infecções por HIV/patologia , Infecções por HIV/fisiopatologia , Atividade Motora/fisiologia , Adulto , Encéfalo/virologia , Função Executiva , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Análise de Regressão , Autorrelato , Transtornos Relacionados ao Uso de Substâncias/patologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologiaRESUMO
Previous studies have identified cognitive impairments due to human immunodeficiency virus (HIV) in adults. However, few studies have examined the impact of HIV on cognition in young adults (18-24 years old). Yet, this group is one of the largest populations of individuals with new HIV infection. Young adulthood is also an important developmental window because the brain has not fully matured and individuals are prone to engage in risky behavior. The purpose of the present study was to examine the impact of HIV on neurocognition and risky behaviors. We hypothesized that HIV+ young adults (n = 23) would exhibit greater cognitive impairment and risky behaviors compared to seronegative controls (n = 21). In addition, we predicted that self-reported risky behavior as assessed by the Risk Assessment Battery (RAB) would covary with cognitive performances. Results revealed poorer executive function in HIV+ young adults compared to seronegative (HIV-) controls. HIV+ young adults exhibited significantly greater risk scores on the RAB (p < 0.01) compared to HIV- young adults. However, there were no relationships between risky behavior and cognitive performance. Overall, our results suggest that HIV is associated with poorer cognition and increased risky behaviors in young adults.
Assuntos
Transtornos Cognitivos/virologia , Infecções por HIV/psicologia , Assunção de Riscos , Adolescente , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Adulto JovemRESUMO
Previous animal studies have identified a C31S residue substitution in the C30C31 dicysteine motif of the Tat protein that is associated with reduced neurovirulence in clade C human immunodeficiency virus (HIV). However, clinical studies of patients infected with clade C HIV have reported significant levels of cognitive impairment. To date, no study has specifically examined cognitive function in clade C-infected patients as a function of the presence or absence of the Tat C31 substitution. The present study investigated the impact of the Tat C30C31S genetic substitution among individuals residing in South Africa infected with clade C HIV that either exhibited the C30C31 motif (n = 128) or the C31S motif (n = 46). A control group of seronegative individuals was included to examine the overall impact of HIV on cognitive performance. All individuals completed a comprehensive neuropsychological battery consisting of tests sensitive to HIV. Results revealed that clade C-infected individuals performed significantly worse across cognitive tests compared to seronegative controls. However, there were no significant differences in cognitive performances between individuals with the C31S motif versus those without the C31S substitution. Proximal CD4 cell count and plasma viral load were unrelated to cognitive performances for either group. Results confirm that the C31S dicysteine motif substitution of the Tat protein does not appreciably moderate neuropsychological outcomes in clade C. Further, these findings highlight the importance of clinical management of cognitive symptoms among individuals infected with this viral clade worldwide.
Assuntos
Substituição de Aminoácidos , Cognição , Genótipo , Infecções por HIV/fisiopatologia , HIV-1/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Adolescente , Adulto , Animais , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Função Executiva , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Masculino , Testes Neuropsicológicos , Tempo de Reação , África do Sul , Carga ViralRESUMO
The biallelic serotonin transporter polymorphism (5-hydroxytryptamine transporter linked polymorphic region (5-HTTLPR)) is a common genetic sequence associated with serotonin transporter (5-hydroxytryptamine transporter (5-HTT)) expression, which is further modulated by a triallelic single-nucleotide polymorphism (rs25531). Recent studies using the biallelic 5-HTTLPR have identified a beneficial role of low 5-HTT expression on cognitive performance, although no studies have examined the impact of the triallelic 5-HTTLPR/rs25531 marker on cognitive performance among healthy older adults. In the present study, we addressed this issue in 84 healthy older adults genotyped for biallelic and triallelic variants of 5-HTT. Groups were created based on low, medium and high levels of expression, as indicated by the triallelic marker. Results indicated that individuals with low 5-HTT expression performed significantly better on a test of memory compared with individuals with medium 5-HTT expression. This suggests that possession of low-expressing genetic variants of 5-HTT is modestly associated with enhanced cognitive performance among healthy older adults.
Assuntos
Cognição/fisiologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polimorfismo Genético/genética , Desempenho Psicomotor/fisiologiaRESUMO
This study examined the neurocognitive and electrophysiological effects of a citicoline-caffeine-based beverage in 60 healthy adult participants enrolled in a randomized, double-blind, placebo-controlled trial. Measures of electrical brain activity using electroencephalogram (EEG) and neuropsychological measures examining attention, concentration and reaction time were administered. Compared to placebo, participants receiving the citicoline-caffeine beverage exhibited significantly faster maze learning times and reaction times on a continuous performance test, fewer errors in a go/no-go task and better accuracy on a measure of information processing speed. EEG results examining P450 event-related potentials revealed that participants receiving the citicoline-caffeine beverage exhibited higher P450 amplitudes than controls, suggesting an increase in sustained attention. Overall, these findings suggest that the beverage significantly improved sustained attention, cognitive effort and reaction times in healthy adults. Evidence of improved P450 amplitude indicates a general improvement in the ability to accommodate new and relevant information within working memory and overall enhanced brain activation.
Assuntos
Atenção/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cafeína/farmacologia , Cognição/efeitos dos fármacos , Citidina Difosfato Colina/farmacologia , Memória de Curto Prazo/efeitos dos fármacos , Nootrópicos/farmacologia , Adulto , Bebidas , Método Duplo-Cego , Eletroencefalografia , Feminino , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Adulto JovemRESUMO
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
This paper reviews basic methods and recent applications of length-based fiber bundle analysis of cerebral white matter using diffusion magnetic resonance imaging (dMRI). Diffusion weighted imaging (DWI) is a dMRI technique that uses the random motion of water to probe tissue microstructure in the brain. Diffusion tensor imaging (DTI) is an extension of DWI that measures the magnitude and direction of water diffusion in cerebral white matter, using either voxel-based scalar metrics or tractography-based analyses. More recently, quantitative tractography based on diffusion tensor imaging (qtDTI) technology has been developed to help quantify aggregate structural anatomical properties of white matter fiber bundles, including both scalar metrics of bundle diffusion and more complex morphometric properties, such as fiber bundle length (FBL). Unlike traditional scalar diffusion metrics, FBL reflects the direction and curvature of white matter pathways coursing through the brain and is sensitive to changes within the entire tractography model. In this paper, we discuss applications of this approach to date that have provided new insights into brain organization and function. We also discuss opportunities for improving the methodology through more complex anatomical models and potential areas of new application for qtDTI.
RESUMO
Aging is associated with microstructural changes in brain tissue that can be visualized using diffusion tensor imaging (DTI). While previous studies have established age-related changes in white matter (WM) diffusion using DTI, the impact of age on gray matter (GM) diffusion remains unclear. The present study utilized DTI metrics of mean diffusivity (MD) to identify age differences in GM/WM microstructure in a sample of healthy older adults (N = 60). A secondary aim was to determine the functional significance of whole-brain GM/WM MD on global cognitive function using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Participants were divided into three age brackets (ages 50-59, 60-69, and 70+) to examine differences in MD and cognition by decade. MD was examined bilaterally in the frontal, temporal, parietal, and occipital lobes for the primary analyses and an aggregate measure of whole-brain MD was used to test relationships with cognition. Significantly higher MD was observed in bilateral GM of the temporal and parietal lobes, and in right hemisphere WM of the frontal and temporal lobes of older individuals. The most robust differences in MD were between the 50-59 and 70+ age groups. Higher whole-brain GM MD was associated with poorer RBANS performance in the 60-69 age group. Results suggest that aging has a significant and differential impact on GM/WM diffusion in healthy older adults, which may explain a modest degree of cognitive variability at specific time points during older adulthood.
Assuntos
Envelhecimento/patologia , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Idoso , Envelhecimento/psicologia , Encéfalo/patologia , Cognição , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes PsicológicosRESUMO
The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n=27, ThrThr n=27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.
Assuntos
Angiotensinogênio/genética , Atenção/fisiologia , Cognição/fisiologia , Idioma , Desempenho Psicomotor/fisiologia , Substância Branca/anatomia & histologia , Idoso , Biomarcadores , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/anatomia & histologia , Vias Neurais/patologia , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Treonina , Substância Branca/patologiaRESUMO
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.
Assuntos
Antirretrovirais/farmacocinética , Terapia Antirretroviral de Alta Atividade , Encéfalo , Sistema Nervoso Central/efeitos dos fármacos , Transtornos Cognitivos/diagnóstico , Infecções por HIV/tratamento farmacológico , Adulto , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Transtornos Cognitivos/etiologia , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Testes NeuropsicológicosRESUMO
OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a brief screening measure commonly used to determine cognitive status among older adults. Despite the popularity of the MoCA, there has been little research into how performance on the MoCA changes over time in healthy older adults. METHODS: The present study examined a sample of older adults (n = 53) recruited for a longitudinal study of healthy aging. Change in total MoCA score at three time points (baseline, 12 months, and 48 months) and scores from the Repeatable Battery for the Assessment of Neuropsychological Status at five time points (RBANS; baseline 12 months, 24 months, 36 months, and 48 months) were assessed using repeated measures analyses. RESULTS: Total MoCA score significantly increased across time, particularly between the first and second administrations. Scores did not significantly differ between the second (12 month) and third (48 month) administrations. When grouped by baseline performance, individuals who scored low at baseline significantly improved performance at 12-month testing, but had little change between 12- and 48-month testing. Conversely, individuals who scored high at baseline did not significantly change between baseline and 12-month testing, but improved between 12- and 48-month testing. RBANS scores did not significantly change over time. CONCLUSIONS: These results suggest that the MoCA may be susceptible to practice effects, particularly between the first and second administrations. These practice effects should be taken into consideration when repeatedly employing the MoCA to screen for cognitive status in healthy older adults.
Assuntos
Cognição/fisiologia , Testes Neuropsicológicos/normas , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos de PesquisaRESUMO
OBJECTIVE: Much of the mild cognitive impairment (MCI) neuroimaging literature has exclusively focused on regions associated with Alzheimer's disease. Little research has examined white matter abnormalities of other brain regions, including those associated with visual processing, despite evidence that other brain abnormalities appear in these regions in early disease stages. METHOD: Diffusion tensor imaging (DTI) was utilized to examine participants (n = 44) that completed baseline imaging as part of a longitudinal healthy aging study. Participants were divided into two groups based on scores from the Montreal Cognitive Assessment (MoCA), a brief screening tool for MCI. Participants who scored <26 were defined as "probable MCI" while those who scored ≥26 were labeled cognitively healthy. Two DTI indices were analyzed including fractional anisotropy (FA) and mean diffusivity (MD). DTI values for white matter in the lingual gyrus, cuneus, pericalcarine, fusiform gyrus, and all four lobes were compared using multivariate analysis of variance (MANOVA). Regression analyses examined the relationship between DTI indices and total MoCA score. RESULTS: RESULTS revealed significantly lower FA in the probable MCI group in the cuneus, fusiform, pericalcarine, and occipital lobe, and significantly higher MD in the temporal lobe. Fusiform FA and temporal lobe MD were significantly related to total MoCA score after accounting for age and education. CONCLUSIONS: RESULTS indicate that there are posterior white matter microstructural changes in individuals with probable MCI. These differences demonstrate that white matter abnormalities are evident among individuals with probable MCI in regions beyond those commonly associated with Alzheimer's disease and anterior brain aging patterns.
Assuntos
Encéfalo/patologia , Disfunção Cognitiva/patologia , Substância Branca/patologia , Idoso , Anisotropia , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Análise de RegressãoRESUMO
Obesity, commonly measured with body mass index (BMI), is associated with numerous deleterious health conditions including alterations in brain integrity related to advanced age. Prior research has suggested that white matter integrity observed using diffusion tensor imaging (DTI) is altered in relation to high BMI, but the integrity of specific white matter tracts remains poorly understood. Additionally, no studies have examined white matter tract integrity in conjunction with neuropsychological evaluation associated with BMI among older adults. The present study examined white matter tract integrity using DTI and cognitive performance associated with BMI in 62 healthy older adults (20 males, 42 females) aged 51-81. Results revealed that elevated BMI was associated with lower fractional anisotropy (FA) in the uncinate fasciculus, though there was no evidence of an age by BMI interaction relating to FA in this tract. No relationships were observed between BMI and other white matter tracts or cognition after controlling for demographic variables. Findings suggest that elevated BMI is associated with lower structural integrity in a brain region connecting frontal and temporal lobes and this alteration precedes cognitive dysfunction. Future studies should examine biological mechanisms that mediate the relationships between BMI and white matter tract integrity, as well as the evolution of these abnormalities utilizing longitudinal designs.
Assuntos
Índice de Massa Corporal , Encéfalo/anatomia & histologia , Cognição/fisiologia , Idoso , Idoso de 80 Anos ou mais , Imagem de Tensor de Difusão , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Memória/fisiologia , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estatística como AssuntoRESUMO
Executive function (EF) and cognitive processing speed (CPS) are two cognitive performance domains that decline with advanced age. Reduced EF and CPS are known to correlate with age-related frontal-lobe volume loss. However, it remains unclear whether white matter microstructure in these regions is associated with age-related decline in EF and/or CPS. We utilized quantitative tractography metrics derived from diffusion-tensor MRI to investigate the relationship between the mean fiber bundle lengths (FBLs) projecting to different lobes, and EF/CPS performance in 73 healthy aging adults. We measured aspects of EF and CPS with the Trail Making Test (TMT), Color-Word Interference Test, Letter-Number Sequencing (L-N Seq), and Symbol Coding. Results revealed that parietal and occipital FBLs explained a significant portion of variance in EF. Frontal, temporal, and occipital FBLs explained a significant portion of variance in CPS. Shorter occipital FBLs were associated with poorer performance on the EF tests TMT-B and CWIT 3. Shorter frontal, parietal, and occipital FBLs were associated with poorer performance on L-N Seq and Symbol Coding. Shorter frontal and temporal FBLs were associated with lower performance on CPS tests TMT-A and CWIT 1. Shorter FBLs were also associated with increased age. Results suggest an age-related FBL shortening in specific brain regions related to poorer EF and CPS performance among older adults. Overall, results support both the frontal aging hypothesis and processing speed theory, suggesting that each mechanism is contributing to age-related cognitive decline.