Differential Methylation in APOE (Chr19; Exon Four; from 44,909,188 to 44,909,373/hg38) and Increased Apolipoprotein E Plasma Levels in Subjects with Mild Cognitive Impairment

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: In total, 100 participants were included (71% women; average age, 70 years; range, 43–91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and APOE methylation. Results: MCI was diagnosed in 41 subjects (average age, 66.5 ± 9.6 years) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (p \u3c 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = −0.665; p = 0.008). Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI

Analysis of cognitive performance and polymorphisms of SORL1, PVRL2, CR1, TOMM40, APOE, PICALM, GWAS_14q, CLU, and BIN1 in patients with mild cognitive impairment and cognitively healthy controls

Introduction: Alzheimer disease risk polymorphisms have been studied in patients with dementia, but have not yet been explored in mild cognitive impairment (MCI) in our population; nor have they been addressed in relation to cognitive variables, which can be predictive biomarkers of disease. Objective: To evaluate cognitive performance and presence of polymorphisms of the genes SORL1(rs11218304), PVRL2(rs6859), CR1(rs6656401), TOMM40(rs2075650), APOE (isoforms ε2, ε3, ε4), PICALM(rs3851179), GWAS_14q(rs11622883), BIN1(rs744373), and CLU(rs227959 and rs11136000) in patients with MCI and healthy individuals. Methodology: We performed a cross-sectional, exploratory, descriptive study of a prospective cohort of participants selected by non-probabilistic sampling, evaluated with neurological, neuropsychological, and genetic testing, and classified as cognitively healthy individuals and patients with MCI. Cognition was evaluated with the Neuronorma battery and analysed in relation to the polymorphic variants by means of measures of central tendency, confidence intervals, and nonparametric statistics. Results: We found differences in performance in language and memory tasks between carriers and non-carriers of BIN1, CLU, and CR1 variants and a trend towards poor cognitive performance for PICALM, GWAS_14q, SORL1, and PVRL2 variants; the APOE and TOMM40 variants were not associated with poor cognitive performance. Discussion: Differences in cognitive performance associated with these polymorphic variants may suggest that the mechanisms regulating these genes could have an effect on cognition in the absence of dementia; however, this study was exploratory and hypotheses based on these results must be explored in larger samples. Resumen: Introducción: Los polimorfismos de riesgo para el desarrollo de enfermedad de Alzheimer se han estudiado en pacientes con demencia, pero aún no se han explorado en trastorno neurocognitivo leve (TNL) en nuestra población, ni se han considerado en relación con variables cognitivas, las cuales pueden ser biomarcadores predictivos de enfermedad. Objetivo: Evaluar los desempeños cognitivos y los polimorfismos en los genes SORL1(rs11218304), PVRL2(rs6859), CR1(rs6656401), TOMM40(rs2075650), APOE(isoformas ε2, ε3, ε4), PICALM(rs3851179), GWAS_14q(rs11622883), BIN(rs744373), CLU (rs227959 y rs11136000) en pacientes con TNL y en sujetos sanos. Metodología: Estudio descriptivo, exploratorio y transversal, en una cohorte prospectiva de participantes seleccionados mediante muestreo no probabilístico, evaluados por neurología, neuropsicología y genética, y clasificados como cognitivamente sanos y pacientes con TNL, según criterios. La cognición se evaluó por medio de la batería Neuronorma y se analizó en relación con las variantes polimórficas por medio de medidas de tendencia, intervalos de confianza y estadísticos no paramétricos. Resultados: Se identificaron diferencias en los desempeños en tareas de lenguaje y memoria en relación con las variantes de BIN1, CLU y CR1, junto con tendencias en las variantes de PICALM, GWArs, SORL y PVRL2, mientras que en APOE y TOMM40 no se encontraron tendencias. Discusión: Las tendencias en los desempeños cognitivos en relación con variantes polimórficas podrían indicar que, en ausencia de demencia, los mecanismos que regulan estos genes podrían tener un efecto sobre la cognición; sin embargo, esta aproximación tiene un carácter exploratorio y sus resultados permiten generar hipótesis que requieren ser exploradas en muestras de mayor tamaño

Funcionalidad y desempeño cognitivo en adultos mayores de 50 años cognitivamente sanos y pacientes con trastorno neurocognitivo leve

Introducción: Las fallas en funcionalidad como criterio en el Trastorno neurocognitivo Leve (TNL) han sido ampliamente estudiadas en la actualidad debido a la poca información que hay frente al tipo y grado de este declive y a la falta de herramientas para su evaluación en la clínica. Los resultados de los estudios son variables, lo que no permite claridad en cuanto a este fenómeno en los pacientes. Se ha encontrado que presentar fallas en funcionalidad en etapas tempranas de declive cognitivo, podría predecir el desarrollo de enfermedades neurodegenerativas. Objetivo: Medir la funcionalidad en un grupo control y en pacientes con TNL a través de la escala Bayer-actividades de la vida diaria, analizando diferencias entre los de las variables sociodemográficas, clínicas y ambientales, y su relación con la cognición, medida con la batería Neuronorma.Co. Metodología: Se seleccionó una muestra de 32 controles y 32 TNL, pareados por edad y escolaridad. Se realizaron pruebas no paramétricas para diferencias de grupo y correlaciones entre las variables. Resultados: No hay diferencias significativas entre los grupos control y TNL para el reporte de la escala Bayer-AVD y así mismo, ésta sólo revela relación significativa con la edad y no muestra relación significativa con las demás variables del estudio. Discusión: Se requieren herramientas sensibles a la detección de cambios tempranos en funcionalidad, ya reportados en TNL. Su estudio debe darse en la evaluación de las tareas paso a paso y no solo su resultado final, para evidenciar los leves cambios en este dominio.Abstract: Introduction: Failures in functionality as a criterion in Mild Neurocognitive Disorder (TNL) have been extensively studied at present, due to the lack of information opposite the type and extent of this decline and the lack of tools for evaluation in the clinic. The results are variable, which does not allow clarity regarding this phenomenon in patients. It has been found that failure to function in early stages of cognitive decline could predict the development of neurodegenerative diseases. Objective: To measure the functionality in a control group and patients with TNL, through the Bayer-activities scale of daily life, analyzing differences between the sociodemographic, clinical and environmental variables, and its relationship with cognition, as measured by the Neuronorma.Co Battery. Methodology: A sample of 32 controls and 32 TNL was selected, matched by age and schooling. Nonparametric tests were performed for group differences and correlations between the variables. Results: There are no significant differences between the control and TNL groups for the report of the Bayer-AVD scale and likewise, this only reveals a significant relationship with age and does not show a significant relationship with the other variables of the study. Discussion: Sensitive tools are required to detect early changes in functionality, already reported in TNL. Your study should be done in the evaluation of the tasks step by step and not only final results, to highlight the slight changes in this domain.Maestrí

Confiability and sensibility of pedsql 4.0™ instrument (pediatric quality of life inventory) in Colombia

Introduction. The aim of this study was to adapt and to assess the reliability of the PedsQL 4.0™ instrument, for measuring pediatric health-related quality of life (HRQoL) in Colombian children. Method. Validation study of measurement instruments. the PedsQL 4.0™ was applied to 375 pairs comprises of children and adolescents between 5 and 17 years old and their parents-caregivers, as well as 125 parents-caregivers of children between 2 and 4 years old in five cities of Colombia (Bogota, Medellin, Cali, Barranquilla and Bucaramanga). Internal consistency, reproducibility and sensitivity to change of the scale were evaluatedDepartamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias1101-569-33208n

Beyond prosody: Foreign accent syndrome in a Spanish-speaking patient. Case report

Introduction: Foreign accent syndrome (FAS) is a rare speech disorder. It is becoming increasingly common to find reports of cases about alterations different from the suprasegmental aspects of speech, although these reports are not frequent in Spanish-speaking patients. Case presentation: 48-year-old female patient from Colombia diagnosed with FAS, segmental and suprasegmental speech alterations, and changes in cognitive domains (executive functions and language). The woman also presented with motor and affective changes. Brain imaging studies ruled out structural involvement and follow-up at one year did not show significant changes in speech. Discussion: This case presents the neurological, neuropsychological and speech features of a Spanish-speaking patient with FAS. Greater alteration in vowels than in consonants, alteration in pronunciation time, variation in rhythm and intonation of words and phrases, decrease of time between syllables, and insertion of vowels are common elements between this patient and other cases of FAS in non-Spanish speaking subjects. Conclusions: FAS is essentially a speech alteration; however, it can be accompanied by other physical and psychological signs. This case report allows recognizing the essential components for the definition, diagnosis and intervention of this syndrome

Cognitive Assessment Test: Validation of a Short Cognitive Test for the Detection of Mild Cognitive Disorder

Introduction. Cognitive disorders are a clinical and research challenge; in particular, the mild cognitive disorder (MiCD) requires diagnostic suspicion and tools with adequate performance for its detection. The objective of this study was the validation of a short cognitive test (CATest) for the detection of MiCD in population of 50 years or more. Methods. A diagnostic accuracy study was assembled and performed in a prospective cohort. A consecutive sample of 200 Colombian subjects who represented the whole spectrum of the condition of interest allowed us to reach the objective. Validity was determined by concurrent criteria. The cut points were determined by the ROC curves considering the best overall performance and accuracy of the test. Results. CATest was validated to detection of MiCD at a cut-off point of 18. As a result, scores lower than 18 classified the participants as MiCD. At this cut-off point, CATest showed sensitivity of 84.3% (CI 76 to 90.16), specificity of 71.4% (CI 95% 61.8 to 79.43), positive predictive value of 75% ( 95% CI 66.79 to 82.42), and area under curve AUC 0.8518 (standard error SE 0.0265). Discussion. CATest has an adequate performance as a short cognitive test for the detection of MiCD. Its performance is superior to MiniMental and similar to Montreal Cognitive test (MoCA) according to the data reported in the literature. The advantages over other tests are the evaluation of all cognitive domains, time of application, and easy interpretation of results. CATest is a free use alternative for MiCD detection

Differential Methylation in <i>APOE</i> (Chr19; Exon Four; from 44,909,188 to 44,909,373/hg38) and Increased Apolipoprotein E Plasma Levels in Subjects with Mild Cognitive Impairment

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: In total, 100 participants were included (71% women; average age, 70 years; range, 43&#8211;91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and APOE methylation. Results: MCI was diagnosed in 41 subjects (average age, 66.5 &#177; 9.6 years) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (p &lt; 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = &#8722;0.665; p = 0.008). Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI

Acute effect of three different exercise training modalities on executive function in overweight inactive men: A secondary analysis of the BrainFit study

7 páginasThere is currently a consensus about the positive effects of physical exercise on cognition. However, the exercise intensity-dependent effect on executive function remains unclear. Thus, the aim of this study was to compare the acute effects of high-intensity aerobic interval training (HIIT), progressive resistance training (PRT), or combined training (PRT + HIIT) on executive function indicators in overweight inactive adult men (aged 18–30 years old). The participants were screened and excluded for medical conditions known to impact cognitive functioning, which was measured with the Montreal Cognitive Assessment (MoCA) screening cognitive test. A randomised, parallel-group clinical trial was conducted among 36 adults who were randomly assigned to a HIIT (n = 12), PRT (n = 7), PRT + HIIT (n = 7), or control group (n = 10) until the energy expenditure of 400–500 kcal. Cognitive inhibition and attention capacity were examined using the Stroop test and d2 test of attention, respectively, and were obtained pre-exercise for baseline measurement and 1 min post-exercise for each exercise training modality. Cognitive inhibition measured by the Stroop test was improved after the HIIT protocol for the domains of reading by +5.89 (η2 = 0.33), colour naming +9.0 (η2 = 0.60), interference +10.1 (η2 = 0.39), and index interference +6.0 (η2 = 0.20). Additionally, the PRT + HIIT group had an increase for the reading condition of +7.1 (η2 = 0.40), colour naming +7.5 (η2 = 0.80), and interference +5.8 (η2 = 0.39). In regard to attentional capacity, the HIIT group elicited small to medium improvements in the concentration level domain of +21.7 (η2 = 0.44), total performance domain +56.6 (η2 = 0.50), and consistency domain −3.0 (η2 = 0.27). These results were similar in the PRT and PRT + HIIT groups in the concentration level and items-processed domains (P < 0.05). In conclusion, acute HIIT and PRT + HIIT sessions reported important effect sizes than PRT alone for cognitive inhibition and attention capacity. Taken together, the results suggest that even short-term exercise interventions can enhance overweight adults' executive functions