Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches.

Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage human immunodeficiency virus (HIV) infection who have commenced antiretroviral treatments (ART). Virtually any opportunistic pathogen can provoke this type of immune restoration disorder. In this review, we focus on recent developments in the identification of risk factors for Cryptococcal IRIS and on advancements in our understanding of C-IRIS immunopathogenesis. We overview new findings in blood and cerebrospinal fluid which can potentially be useful in the prediction and diagnosis of cryptococcal meningitis IRIS (CM-IRIS). We assess current therapeutic regimens and novel treatment approaches to combat CM-IRIS. We discuss the utility of biomarkers for clinical monitoring and adjusting treatment modalities in acquired immunodeficiency syndrome (AIDS) patients co-infected with Cryptococcus who have initiated ART.

Correlation between CSF biomarkers of Alzheimer's disease and global cognition in a psychogeriatric clinic cohort

Objective: The relationship between biomarkers of amyloid-beta aggregation (Aβ1-42) and/or neurodegeneration (Tau protein) in cerebrospinal fluid (CSF) and cognitive decline is still unclear. We aimed to ascertain whether CSF biomarkers correlate with cognitive performance in healthy and cognitively impaired subjects, starting from clinical diagnoses. Methods: We tested for correlation between CSF biomarkers and Mini-Mental State Examination (MMSE) scores in 208 subjects: 54 healthy controls, 82 with mild cognitive impairment (MCI), 46 with Alzheimer's disease (AD), and 26 with other dementias (OD). Results: MMSE correlated weakly with all CSF biomarkers in the overall sample (r = 0.242, p < 0.0006). Aβ1-42 and MMSE correlated weakly in MCI (r = 0.247, p = 0.030), and moderately in OD (r = 0.440, p = 0.027). t-Tau showed a weak inverse correlation with MMSE in controls (r = -0.284, p = 0.043) and MCI (r = -0.241, p = 0.036), and a moderate/strong correlation in OD (r = 0.665), p = 0.0003). p-Tau correlated weakly with MMSE in AD (r = -0.343, p = 0.026) and moderately in OD (r = -0.540, p = 0.0005). The Aβ1-42/p-Tau ratio had a moderate/strong correlation with MMSE in OD (r = 0.597, p = 0.001). Conclusion: CSF biomarkers correlated best with cognitive performance in OD. t-Tau correlated weakly with cognition in controls and patients with MCI. In AD, only p-Tau levels correlated with cognitive performance. This pattern, which has been reported previously, seems to indicate that CSF biomarkers might not be reliable as indicators of disease severity.

Increased CSF levels of total Tau in patients with subcortical cerebrovascular pathology and cognitive impairment / Aumento dos níveis de CSF de Tau total em pacientes com patologia subcutânea cerebrovascular e comprometimento cognitivo

ABSTRACT. Cognitive impairment includes mild cognitive decline and dementia, such as Alzheimer's disease (AD) and cerebrovascular-related pathologies. Objective: To investigate the profile of AD-related CSF biomarkers in a sample of cognitively impaired and unimpaired older adults with concomitant subcortical cerebrovascular burden. Methods: Seventy-eight older adults attending an outpatient psychogeriatric clinic were enrolled. Diagnoses were based on clinical, neuropsychological, laboratory, and neuroimaging data. Participants were classified into: cognitively normal (controls, n = 30), mild cognitive impairment (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF analyses for determination of amyloid-beta (Aß1-42), total tau (t-tau), phosphorylated tau (p-tau) and Aß1-42/p-tau ratio according to the Luminex method. MRI was performed in all individuals, and was scored independently by two experts according to Fazekas scale. Statistical analyses were conducted with the aid of general linear model procedures, and the Chi-squared test. Results: T-tau levels were significantly associated with subcortical lesion pattern when Fazekas was considered as a group factor. CSF biomarkers were not associated with MCI, AD, or controls when considered separately. There was a tendency for reduction in CSF Aß1-42 together with increasing Fazekas scores, but without statistical significance. Comparisons of Aß1-42 and t-tau with each clinical group or with each neuroimaging pattern did not reach statistical differences. Likewise, Fazekas scores had no impact on CAMCOG scores. Conclusion: We found a significant association between t-tau levels and subcortical lesions when all Fazekas classifications were considered as a single group; comparisons of Fazekas subgroups and CSF biomarkers did not reach significance.

RESUMO. O comprometimento cognitivo inclui alterações leves da cognição e demência, como doença de Alzheimer (DA) e patologias vasculares associadas. Objetivo: Investigar o perfil de biomarcadores da DA no líquor e doença cerebrovascular concomitante em idosos com e sem alterações cognitivas. Métodos: Foram incluídos 78 sujeitos de um ambulatório de psicogeriatria. Efetuaram-se os diagnósticos com base em dados clínicos, neuropsicológicos, laboratoriais e neuroimagem. Os participantes foram classificados em: cognitivamente normais (controles, n = 30), comprometimento cognitivo leve (CCL, n = 34) e demência (DA, n = 14). Todos foram submetidos ao exame liquórico para determinação de ß-amiloide (Aß1-42), tau total (t-tau), tau fosforilada (p-tau) e razão Aß1-42/p-tau, segundo o método de Luminex. RM foi efetuada em todos os indivíduos. Dois especialistas independentes avaliaram as imagens segundo a escala de Fazekas. As análises estatísticas basearam-se em modelo linear geral e teste qui-quadrado. Resultados: T-tau foi significantemente associada ao padrão de lesão subcortical quando o grau de Fazekas foi considerado como fator grupal. Não houve associação entre biomarcadores e diagnóstico clínico de CCL, DA e grupo controle, considerados individualmente. Observou-se uma tendência de redução de Aß1-42 concomitante com elevação dos escores de Fazekas, sem correlação significante. Comparações entre Aß1-42 e tau e diagnóstico clínico ou neuroimagem não foram significantes. Os resultados de Fazekas não influenciaram os escores do CAMCOG. Conclusão: Como principal resultado, observou-se associação significante entre os níveis de t-tau e lesões subcorticais quando as classificações de Fazekas foram incluídas em um único grupo. As comparações dos subgrupos de Fazekas e biomarcadores liquóricos não foram significantes.

Increased CSF levels of total Tau in patients with subcortical cerebrovascular pathology and cognitive impairment.

Cognitive impairment includes mild cognitive decline and dementia, such as Alzheimer's disease (AD) and cerebrovascular-related pathologies. OBJECTIVE: To investigate the profile of AD-related CSF biomarkers in a sample of cognitively impaired and unimpaired older adults with concomitant subcortical cerebrovascular burden. METHODS: Seventy-eight older adults attending an outpatient psychogeriatric clinic were enrolled. Diagnoses were based on clinical, neuropsychological, laboratory, and neuroimaging data. Participants were classified into: cognitively normal (controls, n = 30), mild cognitive impairment (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF analyses for determination of amyloid-beta (Aß1-42), total tau (t-tau), phosphorylated tau (p-tau) and Aß1-42/p-tau ratio according to the Luminex method. MRI was performed in all individuals, and was scored independently by two experts according to Fazekas scale. Statistical analyses were conducted with the aid of general linear model procedures, and the Chi-squared test. RESULTS: T-tau levels were significantly associated with subcortical lesion pattern when Fazekas was considered as a group factor. CSF biomarkers were not associated with MCI, AD, or controls when considered separately. There was a tendency for reduction in CSF Aß1-42 together with increasing Fazekas scores, but without statistical significance. Comparisons of Aß1-42 and t-tau with each clinical group or with each neuroimaging pattern did not reach statistical differences. Likewise, Fazekas scores had no impact on CAMCOG scores. CONCLUSION: We found a significant association between t-tau levels and subcortical lesions when all Fazekas classifications were considered as a single group; comparisons of Fazekas subgroups and CSF biomarkers did not reach significance.

O comprometimento cognitivo inclui alterações leves da cognição e demência, como doença de Alzheimer (DA) e patologias vasculares associadas. OBJETIVO: Investigar o perfil de biomarcadores da DA no líquor e doença cerebrovascular concomitante em idosos com e sem alterações cognitivas. MÉTODOS: Foram incluídos 78 sujeitos de um ambulatório de psicogeriatria. Efetuaram-se os diagnósticos com base em dados clínicos, neuropsicológicos, laboratoriais e neuroimagem. Os participantes foram classificados em: cognitivamente normais (controles, n = 30), comprometimento cognitivo leve (CCL, n = 34) e demência (DA, n = 14). Todos foram submetidos ao exame liquórico para determinação de ß-amiloide (Aß1-42), tau total (t-tau), tau fosforilada (p-tau) e razão Aß1-42/p-tau, segundo o método de Luminex. RM foi efetuada em todos os indivíduos. Dois especialistas independentes avaliaram as imagens segundo a escala de Fazekas. As análises estatísticas basearam-se em modelo linear geral e teste qui-quadrado. RESULTADOS: T-tau foi significantemente associada ao padrão de lesão subcortical quando o grau de Fazekas foi considerado como fator grupal. Não houve associação entre biomarcadores e diagnóstico clínico de CCL, DA e grupo controle, considerados individualmente. Observou-se uma tendência de redução de Aß1-42 concomitante com elevação dos escores de Fazekas, sem correlação significante. Comparações entre Aß1-42 e tau e diagnóstico clínico ou neuroimagem não foram significantes. Os resultados de Fazekas não influenciaram os escores do CAMCOG. CONCLUSÃO: Como principal resultado, observou-se associação significante entre os níveis de t-tau e lesões subcorticais quando as classificações de Fazekas foram incluídas em um único grupo. As comparações dos subgrupos de Fazekas e biomarcadores liquóricos não foram significantes.