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Background: The largest identified kindred worldwide with a single mutation causing autosomal-dominant Alzheimer's disease (ADAD) is a family from Antioquia, Colombia, carrying the Presenilin-1 (PSEN1) E280A (Paisa) mutation. The majority of mutation carriers develop dementia, typically commencing in their late 30 s, with a median onset age of 49 years. Cognitive decline is a hallmark feature. Objective: This review synthesizes the existing literature on neuropsychological assessments in PSEN1 E280A mutation carriers throughout their lifespan. We provide a comprehensive overview of cognitive outcomes in this unique population. Methods: We reviewed and integrated the published research, analyzing studies on neuropsychological assessments in PSEN1 E280A carriers. Our focus was on measures of verbal, semantic, episodic, and spatial memory, and encompassed other cognitive domains such as language, attention, visuospatial memory, and executive functioning. Results: Verbal, semantic, episodic, and spatial memory emerged as the most sensitive indicators of preclinical changes in PSEN1 E280A carriers. Inconsistencies were noted in findings from tests assessing language, attention, visuospatial memory, and executive functioning, suggesting potential limitations in detecting early cognitive changes in PSEN1 mutation carriers. Specific cognitive tasks developed for this population proved effective but underutilized. Conclusions: The review underscores the importance of continued test development tailored to detect early cognitive changes in PSEN1 E280A carriers, potentially enhancing ADAD screening. Furthermore, investigating ADAD mutations in children may identify early changes in AD and enhance our understanding of neuropsychological functioning across the lifespan. This synthesis provides valuable insights for researchers, clinicians, and policymakers engaged in the study and management of ADAD.

Asunto(s)

Enfermedad de Alzheimer , Mutación , Pruebas Neuropsicológicas , Presenilina-1 , Humanos , Presenilina-1/genética , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Colombia , Mutación/genética , Disfunción Cognitiva/genética , Cognición/fisiología

RESUMEN

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Asunto(s)

Enfermedad de Alzheimer , Apolipoproteína E3 , Presenilina-1 , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Edad de Inicio , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Apolipoproteína E3/genética , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Colombia , Familia , Genes Dominantes , Heterocigoto , Tomografía de Emisión de Positrones , Presenilina-1/genética , Estudios Retrospectivos

RESUMEN

BACKGROUND: Self-Compassion is crucial for assessing how people relate to their suffering in moments of personal difficulty. The objective of this study was to check the psychometric properties of the Self-Compassion Scale (SCS) in a Colombian sample. METHOD: The Spanish version of the SCS was adapted to the Colombian context via a content validity technique. This version was administered to 751 Colombians from the general community. Psychometric analysis was performed using R studio packages. RESULTS: 7 models were tested, the best fit was found for the bifactor ESEM model (χ2/df = 0.86, CFI = 1, TLI= 1, RMSEA= 0.00, SRMR= 0.01). This model produced optimal reliability indices (ωh = 0.83, FD= 0.93, H= 0.96). CONCLUSIONS: The study produced initial psychometric evidence of the structure of the SCS in Colombia, with evidence of a general factor in the bifactor ESEM model. More research is needed to justify the complete usage of the SCS in the country.

Asunto(s)

Empatía , Autocompasión , Humanos , Reproducibilidad de los Resultados , Colombia , Psicometría/métodos , Encuestas y Cuestionarios

RESUMEN

BACKGROUND: Cigarette smoking is a known risk factor for Alzheimer's disease (AD). However, the association between neurodegeneration and other substances has not been fully determined. It is of vital importance to evaluate this relationship in populations at high risk of dementia. Since substance use possibly modifies the progression rate of cognitive decline, we studied this association in a unique and well-phenotyped cohort from the University of Antioquia: carriers of the PSEN1-E280A genetic variant. OBJECTIVE: To determine the association between substance use and cognitive decline in carriers of the PSEN1-E280A genetic variant. METHODS: A retrospective cohort study was conducted with 94 carriers and 69 noncarriers recruited between January 2019 and April 2020. A psychiatrist interviewed the participants using the Consumption of Alcohol, Cigarettes and other Substances questionnaire. The participants were also submitted to cognitive evaluation. The relationship between cognitive decline and substance use was explored through a mixed effects regression model. RESULTS: There was an association between cigarettes and better performance on tasks related to perceptual organization, verbal fluency, and memory in carriers. Alcohol had a positive or negative effect on memory according to the type of alcoholic beverage. Results on marijuana use were no conclusive. Coffee was associated with progressive improvements in executive function and verbal fluency. CONCLUSION: Cigarette and alcohol were associated with an improvement of some cognitive assessments, possibly by a survival bias. In addition, coffee was related to improvements in executive function and language; therefore, its short-term neuroprotective potential should be studied.

Asunto(s)

Enfermedad de Alzheimer/genética , Disfunción Cognitiva/epidemiología , Presenilina-1/genética , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Fumar Cigarrillos/epidemiología , Colombia/epidemiología , Función Ejecutiva , Femenino , Heterocigoto , Humanos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Estudios Retrospectivos , Encuestas y Cuestionarios

RESUMEN

OBJECTIVE: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer's disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world's largest ADAD kindred and sex differences in the relationship between SCD and memory performance. METHODS: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. RESULTS: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. CONCLUSIONS: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

Asunto(s)

Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/complicaciones , Disfunción Cognitiva/psicología , Estudios de Cohortes , Colombia , Femenino , Heterocigoto , Humanos , Masculino , Pruebas Neuropsicológicas , Factores Sexuales

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PURPOSE: We carried out a randomized, clinical trial in adults of both sexes with metabolic syndrome (MS) to assess the efficacy of high-intensity, low-volume interval training (HIIT) compared to moderate-intensity continuous training (MICT) on insulin resistance (IR), muscle mass, muscle activation, and serum musclin. METHODS: Fasting glycemia, insulinemia, and glycated haemoglobin were determined by conventional methods, IR by Homeostatic model assessment (HOMA), lean mass by Dual-Energy X-ray Absorptiometry, muscle activation through carnosine by Proton Magnetic Resonance Spectroscopy, and musclin by Enzyme-Linked ImmunoSorbent Assay before and after a supervised, three-times/week, 12-week treadmill programme. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). MICT (n = 31) trained at 60% of VO2peak for 30 min. RESULTS: Patients had a mean age of 50.8 ± 6.0 years, body mass index of 30.6 ± 4.0 kg/m2, and VO2peak of 29.0 ± 6.3 mL.kg-1.min-1. Compared to MICT, HIIT was not superior at reducing Ln HOMA-IR (adjusted mean difference: 0.083 [95%CI - 0.092 to 0.257]), carnosine or musclin or at increasing thigh lean mass. HIIT increased carnosine by 0.66 mmol/kg.ww (95% CI 0.08-1.24) after intervention. Both interventions reduced IR, body fat percentage and increased total lean mass/height2 and VO2peak. Musclin showed a non-significant reduction with a small effect size after both interventions. CONCLUSION: Compared to MICT, HIIT is not superior at reducing IR, carnosine or musclin or at increasing skeletal muscle mass in adults with MS. Both training types improved IR, muscle mass and body composition. NCT03087721, March 22nd, 2017. TRIAL REGISTRATION NUMBER: NCT03087721. Registered March 22nd, 2017.

Asunto(s)

Entrenamiento de Intervalos de Alta Intensidad , Resistencia a la Insulina/fisiología , Síndrome Metabólico/prevención & control , Síndrome Metabólico/fisiopatología , Adulto , Biomarcadores/sangre , Carnosina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Musculares/sangre , Factores de Transcripción/sangre

RESUMEN

INTRODUCTION: Cortical thinning is a marker of neurodegeneration in Alzheimer's disease (AD). We investigated the age-related trajectory of cortical thickness across the lifespan (9-59 years) in a Colombian kindred with autosomal dominant AD (ADAD). METHODS: Two hundred eleven participants (105 presenilin-1 [PSEN1] E280A mutation carriers, 16 with cognitive impairment; 106 non-carriers) underwent magnetic resonance imaging. A piecewise linear regression identified change-points in the age-related trajectory of cortical thickness in carriers and non-carriers. RESULTS: Unimpaired carriers exhibited elevated cortical thickness compared to non-carriers, and thickness more negatively correlated with age and cognition in carriers relative to non-carriers. We found increased cortical thickness in child carriers, after which thickness steadied compared to non-carriers prior to a rapid reduction in the decade leading up to the expected age at cognitive impairment in carriers. DISCUSSION: Findings suggest that cortical thickness may fluctuate across the ADAD lifespan, from early-life increased thickness to atrophy proximal to clinical onset.

RESUMEN

Importance: We previously reported that children with the autosomal dominant Alzheimer disease (ADAD) presenilin 1 (PSEN1) E280A variant had early life plasma biomarker findings consistent with amyloid ß overproduction. However, the cognitive functioning of children with this variant has not been characterized vs those without the variant. Objective: To test whether cognitive functioning of children with and without the PSEN1 E280A variant in the same ADAD cohort differed by genetic status (ie, PSEN1 variant) and sex. Design, Setting, and Participants: This cohort study was conducted among 1354 children (including 265 children with the variant) aged 6 to 16 years recruited from the Alzheimer Prevention Initiative Colombia Registry. Participants from the city of Medellín and surrounding suburban areas traveled to the University of Antioquia to undergo all procedures. Participants were administered a Spanish version of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) to measure general cognitive functioning. Data were analyzed from July through November 2020. Main Outcomes and Measures: Univariate general linear models were used to characterize differences on WISC-IV cognitive performance by genetic status, sex, and the interaction of genetic status with sex. Urbanity, socioeconomic status, and education were entered as covariates. Results: Among 1354 children with ADAD (695 [51.3%] girls; mean [SD] age, 11.64 [2.64] years), there were 265 children with the variant (19.6%) and 1089 children without the variant (80.4%). Children with and without the variant did not differ by demographic variables or performance on WISC-IV indices. Irrespective of genetic status, boys had statistically significantly decreased mean scores on indices for working memory (90.27 [95% CI, 89.21-91.34] vs 92.99 [95% CI, 91.98-93.99]; mean difference = -2.72; P < .001), perceptual reasoning (91.56 [95% CI, 90.47-92.65] vs. 93.27 [95% CI, 91.23-94.30]; mean difference = -1.71; P = .03), and verbal comprehension (88.69 [95% CI, 87.54-89.84] vs. 90.81 [95% CI, 89.73-91.90]; mean difference = -2.12; P = .009) compared with girls. In the interaction between sex and genetic status, boys with the variant had worse mean working memory index performance (88.78 [95% CI, 86.86-90.70]) than girls with the variant (93.75 [95% CI, 91.95-95.55]; mean difference = -4.97; P = .001), as well as boys (91.77 [95% CI, 90.85-92.70]; mean difference = -2.99; P = .04) and girls (92.22 [95% CI, 91.32-93.13]; mean difference = -3.44; P = .009) without the variant. Conclusions and Relevance: This study found that boys with the PSEN1 variant had decreased working memory abilities compared with girls with the variant and boys and girls without the variant, suggesting a sex-specific genetic risk in early life cognitive performance among individuals with the PSEN1 variant. This increased risk of future cognitive difficulties among boys with the variant may have important downstream implications for learning and academic achievement and could be associated with sex differences seen in adulthood on episodic memory measures.

Asunto(s)

Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Trastornos del Conocimiento/genética , Predisposición Genética a la Enfermedad , Valor Predictivo de las Pruebas , Presenilinas/sangre , Presenilinas/genética , Adolescente , Adulto , Edad de Inicio , Biomarcadores/sangre , Niño , Trastornos del Conocimiento/sangre , Estudios de Cohortes , Colombia , Femenino , Voluntarios Sanos , Humanos , Masculino , Factores Sexuales

RESUMEN

OBJECTIVE: Validate the Self Stigma Of Seeking Help (SSOSH) scale in a population of students of a medical school for its use in Colombia. METHODS: We included 384 medical students from the city of Medellín. Initially, two direct translations were made, two back translation and one pilot test. The internal consistency, test-retest repeatability and structural, convergent, divergent and discriminative construct validity were then evaluated. RESULTS: A easy-to-understand and to fill out Spanish version was obtained. The internal consistency of the scale was adequate (Cronbach's alpha = .80; 95%CI, .77-.83) as well as the test-retest repeatability (CCI = .77; 95%CI, .63-.86). The Confirmatory Factor Analysis showed a good fit with the one-dimensional structure (RMSEA = .073; IC90%, .056-.089; CFI = .968; TLI = .977; WRMR = .844). The convergent validity was supported by the correlation with the Public Stigma scales (ρ = .39) and Attitudes towards Seeking Help (ρ = -0.50) and the divergent validity with the Social Desirability scale (ρ = -0,05). When examining the discriminative validity, differences were found between the scores of those who would be willing to seek professional help when having a mental health problem and those who probably would not (Difference of means = 4.9; 95%CI, 2.99-6.83). CONCLUSIONS: The Colombian version of the SSOSH is valid, reliable and useful for the measurement of the Self-stigma associated with seeking professional help in the university population of the Colombian health sector. Its psychometric properties must be investigated in populations of other programs and outside universities.

Asunto(s)

Estudiantes de Medicina , Colombia , Humanos , Psicometría , Estigma Social , Encuestas y Cuestionarios

RESUMEN

RESUMEN Objetivo: Validar la escala de Autoestigma por Búsqueda de Ayuda (ABA), conocida en inglés como Self-Stigma of Seeking Help (SSOSH), en una población de estudiantes de una facultad de Medicina para su uso en Colombia. Método: Se incluyó a 384 estudiantes de Medicina de la ciudad de Medellín. Se realizaron 2 traducciones directas, 2 en sentido inverso y 1 prueba piloto. Luego se evaluó la consistencia interna, la reproducibilidad prueba-reprueba y la validez del constructo estructural, convergente, divergente y discriminativa. Resultados: Se obtuvo una versión en español de fácil comprensión y diligenciamiento. La consistencia interna de la escala fue adecuada (alfa de Cronbach = 0,80; IC95%, 0,77-0,83) al igual que la reproducibilidad prueba-reprueba (CCI = 0,77; IC95%, 0,63-0,86). El análisis factorial confirmatorio mostró un buen ajuste con la estructura unidimensional (RMSEA = 0,073; IC90%, 0,056-0,089; CFI = 0,968; TLI = 0,977; WRMR = 0,844). La validez convergente se mantuvo con la correlación con las escalas de estigma público (p = 0,39) y de actitudes hacia la búsqueda de ayuda (p = -0,50) y la validez divergente con la escala de deseabilidad social (p = -0,05). Al examinar la validez discriminativa, se encontraron diferencias significativas entre las puntuaciones de quienes estarían dispuestos a buscar ayuda profesional en caso de tener un problema de salud mental y quienes probablemente no lo harían (diferencia de medias, 4,9; IC95%, 2,99-6,83). Conclusiones: La versión colombiana de la ABA es válida, confiable y útil para la medición del autoestigma asociado con la búsqueda de ayuda profesional en población universitaria del área de la salud de Colombia. Se debe investigar sus propiedades psicométricas en poblaciones de otros programas y no universitarias.

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ABSTRACT Objective: Validate the Self Stigma Of Seeking Help (SSOSH) scale in a population of students of a medical school for its use in Colombia. Methods: We included 384 medical students from the city of Medellín. Initially, two direct translations were made, two back translation and one pilot test. The internal consistency, test-retest repeatability and structural, convergent, divergent and discriminative construct validity were then evaluated. Results: A easy-to-understand and to fill out Spanish version was obtained. The internal consistency of the scale was adequate (Cronbach's alpha = .80; 95%CI, .77-.83) as well as the test-retest repeatability (CCI = .77; 95%CI, .63-.86). The Confirmatory Factor Analysis showed a good fit with the one-dimensional structure (RMSEA = .073; IC90%, .056-.089; CFI = .968; TLI = .977; WRMR= .844). The convergent validity was supported by the correlation with the Public Stigma scales (p=.39) and Attitudes towards Seeking Help (p= -0.50) and the divergent validity with the Social Desirability scale (p=-0,05). When examining the discriminative validity, differences were found between the scores of those who would be willing to seek professional help when having a mental health problem and those who probably would not (Difference of means = 4.9; 95%CI, 2.99-6.83). Conclusions: The Colombian version of the SSOSH is valid, reliable and useful for the measurement of the Self-stigma associated with seeking professional help in the university population of the Colombian health sector. Its psychometric properties must be investigated in populations of other programs and outside universities.

RESUMEN

OBJECTIVE: Validate the Self Stigma Of Seeking Help (SSOSH) scale in a population of students of a medical school for its use in Colombia. METHODS: We included 384 medical students from the city of Medellín. Initially, two direct translations were made, two back translation and one pilot test. The internal consistency, test-retest repeatability and structural, convergent, divergent and discriminative construct validity were then evaluated. RESULTS: A easy-to-understand and to fill out Spanish version was obtained. The internal consistency of the scale was adequate (Cronbach's alpha=.80; 95%CI, .77-.83) as well as the test-retest repeatability (CCI=.77; 95%CI, .63-.86). The Confirmatory Factor Analysis showed a good fit with the one-dimensional structure (RMSEA=.073; IC90%, .056-.089; CFI=.968; TLI=.977; WRMR=.844). The convergent validity was supported by the correlation with the Public Stigma scales (ρ=.39) and Attitudes towards Seeking Help (ρ= -0.50) and the divergent validity with the Social Desirability scale (ρ=-0,05). When examining the discriminative validity, differences were found between the scores of those who would be willing to seek professional help when having a mental health problem and those who probably would not (Difference of means=4.9; 95%CI, 2.99-6.83). CONCLUSIONS: The Colombian version of the SSOSH is valid, reliable and useful for the measurement of the Self-stigma associated with seeking professional help in the university population of the Colombian health sector. Its psychometric properties must be investigated in populations of other programs and outside universities.

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Neuropsychologists continue to face challenges when assessing Spanish-speaking individuals due to limited availability of normative data. We developed comprehensive normative data stratified by age and education for a Spanish neuropsychological test battery used by the Grupo de Neurociencias de Antioquia (Colombia) and the Colombian Alzheimer's Prevention Initiative Registry, which have followed large families at risk for autosomal-dominant Alzheimer's disease (ADAD) since the 1990s. Approximately 75% of these individuals are cognitively-unimpaired and are not genetically predisposed to develop ADAD. We conducted a retrospective study on neuropsychological evaluations from 2,673 cognitively unimpaired individuals (56% female), with ages ranging from 18 to 86 years and education from 1 to 25 years. Neuropsychological measures included the Consortium to Establish a Registry for Alzheimer's Disease-Colombia, and other multidomain Spanish tests. We examined associations between age, education, and sex with cognitive performance. Norms stratified by age and education are presented. Cognitive performance showed small associations with age and education and was unrelated to sex. We provided population-based norms for Spanish tests targeting multiple cognitive domains using a large Colombian sample. These normative data may be helpful for the neuropsychological characterization of Spanish speakers from Latin America in clinical and research settings.

Asunto(s)

Enfermedad de Alzheimer , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Colombia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valores de Referencia , Sistema de Registros , Estudios Retrospectivos , Adulto Joven

RESUMEN

BACKGROUND: Dementia of the Alzheimer's type (DAT) impacts Hispanics disproportionately, with almost a twofold elevated risk of developing DAT, as well as earlier onset of the disease, than in non-Hispanic Whites. However, the role of main risk factors for DAT, such as APOE-ɛ4 and blood pressure (BP) levels, remains uncertain among Hispanics. OBJECTIVE: To investigate the association of APOE-ɛ4 and BP levels, measures with 24-h ambulatory BP monitoring, with incidence of DAT in an elderly cohort of Hispanics. METHODS: 1,320 participants from the Maracaibo Aging Study, free of dementia at the baseline, and with ambulatory BP measurements and APOE genotype available were included. Adjusted Cox proportional models were performed to examine 1) the incidence of DAT and 2) the relationship between BP levels and DAT according to APOE genotypes. Models were adjusted by competing risk of death before the onset of DAT. Model performance was assessed by likelihood test. RESULTS: The average follow-up time was 5.3 years. DAT incidence was 5.8 per 1000 person-year. APOE-ɛ4 carriers had a higher risk of DAT. In unadjusted analyses, conventional, 24-h, and nighttime systolic BP levels were significantly higher in participants who developed DAT and of APOE-ɛ4 carriers (p < 0.05). After adjustment for competing risks, only higher nighttime systolic BP was associated with DAT incidence, but only among subjects carrying APOE-ɛ4. CONCLUSION: In this Hispanic population, both APOE-ɛ4 genotype and assessment of nocturnal systolic BP (rather than diurnal or office BP) were necessary to estimate DAT risk.

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Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Presión Sanguínea/genética , Ritmo Circadiano/genética , Demencia/genética , Genotipo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/etnología , Demencia/diagnóstico , Demencia/etnología , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Venezuela/etnología

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INTRODUCTION: The prevalence and incidence of amyotrophic lateral sclerosis (ALS) is not fully established, and this varies depending on the studied population. OBJECTIVE: To estimate the prevalence/incidence of ALS patients in Antioquia-Colombia. METHODOLOGY: Observational/descriptive study by reviewing clinical records from 2010 to 2014. Cases with possible, probable and definite ALS were included. To estimate the prevalence/incidence, capture-recapture method was used. RESULTS: Point prevalence in December 2014 was 4.9/100,000 (95% CI 2.0-7.8), and the incidence was 1.4/100,000/year (95% CI 0.5-2.2). The median survival was 4 years. Spinal-onset was observed in 62.4% of the included patients. CONCLUSION: Prevalence, incidence and clinical presentation of ALS in Antioquia are similar to most studies reported worldwide. However, prevalence in Antioquia seems to be slightly higher than in other studies from Latin -American countries. This may derive from the inclusion criteria and case detection methodology adopted, but sociodemographic and genetic factors should be considered.

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Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/epidemiología , Sistema de Registros/estadística & datos numéricos , Edad de Inicio , Anciano , Colombia/epidemiología , Diagnóstico Tardío/estadística & datos numéricos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos

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INTRODUCTION: A small percentage of Alzheimer's disease (AD) cases are caused by genetic mutations with autosomal dominant inheritance. We report a family with a novel variant in PSEN1. METHODS: We performed clinical and genetic evaluation of 93 related individuals from a Colombian admixed population. 31 individuals had whole-genome sequencing. RESULTS: Genetic analysis revealed a missense variant in PSEN1 (NM_000021.3: c.1247T>C p.Ile416Thr), which originated on an African haplotype and segregated with AD logarithm of the odds score of 6. Their clinical phenotype is similar to sporadic AD except for earlier age at onset: the mean age at onset for mild cognitive impairment was 47.6 years (standard deviation 5.83) and for dementia 51.6 years (standard deviation 5.03). DISCUSSION: Ile416Thr is a novel pathogenic variant that causes AD in the sixth decade of life. The history of the region that included slave importation and admixtures within a confined geographic locale represents a "mini-population bottleneck" and subsequent emergence of a rare dominant mutation.

Asunto(s)

Edad de Inicio , Enfermedad de Alzheimer/genética , Mutación Missense/genética , Presenilina-1/genética , Adulto , Colombia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Secuenciación Completa del Genoma

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BACKGROUND: There is minimal information available about acute hepatic porphyrias (AHPs) in developing countries. The aim of this study was to describe the demographics, clinical features, and mortality of AHPs in Colombia. PATIENTS AND METHODS: 121 patients with presumed diagnosis of AHPs were reported in Colombia between 1944 and 2018. A pooled analysis of 53 patients with confirmed diagnosis was performed to evaluate the demographics, clinical features, and mortality of AHPs in the country. Selected variables were compared by periods (1952-2000 and 2001-2018). RESULTS: Most attacks occurred in women (66%), with a women-to-man ratio of 39/14. 96% of the patients were diagnosed with AHPs between 15 and 40 years of age. Precipitants were identified in 71% of attacks and more than one precipitant in 41% of them. Drugs (85%) and infections (44%) were the most common precipitants. 11% of women had premenstrual attacks. Abdominal pain was the most common symptom (96%). Cortical blindness, posterior reversible encephalopathy syndrome, and rhabdomyolysis were described. 70% of attacks were confirmed by qualitative test only. 67% of attacks were treated with intravenous heme. The use of heme increased from 4 to 85% in the last two decades. Mortality decreased about twofold in relation to the increase in the use of heme. Severe motor neuropathy was associated with increased mortality. Gonadorelin analogues, heme prophylaxis, and orthotopic liver transplantation have been used to prevent recurrent attacks. CONCLUSIONS: Diagnosis and treatment of AHPs in Colombia have improved in recent decades. However, there are still important shortcomings to address.

RESUMEN

BACKGROUND: There is a need to find cognitive markers that can help identify individuals at risk for Alzheimer's disease (AD), and that can be used to reliably measure cognitive decline. OBJECTIVE: We tested whether a theoretically driven three-factor structure would characterize cognitive functioning in individuals who are genetically-determined to develop AD due to a mutation in Presenilin-1 (PSEN1) gene. We also examined whether these factors could distinguish cognitively unimpaired PSEN1 mutation carriers from age-matched non-carrier family members. METHODS: 1,395 cognitively unimpaired members of a Colombian kindred with the PSEN1 E280A mutation were included in the study. A confirmatory factor analysis examined the fit of the three-factor model comprising episodic memory (MMSE memory recall, CERAD-COL Word list recall, and Constructional praxis recall), executive function (Phonemic fluency and WCST perseverative errors), and psychomotor processing speed (TMT-A and WAIS-III Digit Symbol). RESULTS: The three-factor model provided an excellent fit for all participants (p = 0.24; RMSEA = 0.01). Further, the episodic memory (p = 0.0004, d = 0.25) and executive functioning (p = 0.001, d = 0.18) factors distinguished cognitively unimpaired carriers from non-carriers. The episodic memory factor provided the earliest indication of preclinical cognitive decline at 35 years of age, nine years before individuals' estimated age of clinical onset. CONCLUSIONS: The three theoretically derived cognitive factors provide a reliable measure of cognition and may be useful for the early detection of AD, as well as for measuring disease progression. However, longitudinal studies are needed to confirm that these factors can be used to track the progression of cognitive decline in preclinical AD.

Asunto(s)

Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/genética , Disfunción Cognitiva/etiología , Mutación/genética , Presenilina-1/genética , Adolescente , Adulto , Colombia , Función Ejecutiva/fisiología , Análisis Factorial , Femenino , Humanos , Masculino , Memoria Episódica , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Adulto Joven

RESUMEN

BACKGROUND: Evidence of the efficacy of high-intensity, low-volume interval training (HIIT-low volume) in treating insulin resistance (IR) in patients with metabolic disorders is contradictory. In addition, it is unknown whether this effect is mediated through muscle endocrine function, which in turn depends on muscle mass and fiber type composition. Our aims were to assess the efficacy of HIIT-low volume compared to continuous aerobic exercise (CAE) in treating IR in adults with metabolic syndrome (MS) and to establish whether musclin, apelin, muscle mass and muscle composition are mediators of the effect. METHODS: This is a controlled, randomized, clinical trial using the minimization method, with blinding of those who will evaluate the outcomes and two parallel groups for the purpose of showing superiority. Sixty patients with MS and IR with ages between 40 and 60 years will be included. A clinical evaluation will be carried out, along with laboratory tests to evaluate IR (homeostatic model assessment (HOMA)), muscle endocrine function (serum levels of musclin and apelin), thigh muscle mass (by dual energy x-ray absorptiometry (DXA) and thigh muscle composition (by carnosine measurement with proton magnetic resonance spectroscopy (1H-MRS)), before and after 12 weeks of a treadmill exercise program three times a week. Participants assigned to the intervention (n = 30) will receive HIIT-low volume in 22-min sessions that will include six intervals at a load of 90% of maximum oxygen consumption (VO2 max) for 1 min followed by 2 min at 50% of VO2 max. The control group (n = 30) will receive CAE at an intensity of 60% of VO2 max for 36 min. A theoretical model based on structural equations will be proposed to estimate the total, direct and indirect effects of training on IR and the proportion explained by the mediators. DISCUSSION: Compared with CAE, HIIT-low volume can be effective and efficient at improving physical capacity and decreasing cardiovascular risk factors, such as IR, in patients with metabolic disorders. Studies that evaluate mediating variables of the effect of HIIT-low volume on IR, such as endocrine function and skeletal muscle structure, are necessary to understand the role of skeletal muscle in the pathophysiology of MS and their regulation by exercise. TRIAL REGISTRATION: NCT03087721 . High-intensity Interval, Low Volume Training in Metabolic Syndrome (Intraining-MET). Registered on 22 March 2017, retrospectively registered.

Asunto(s)

Ejercicio Físico , Entrenamiento de Intervalos de Alta Intensidad/métodos , Resistencia a la Insulina , Síndrome Metabólico/terapia , Músculo Esquelético/fisiopatología , Absorciometría de Fotón , Adulto , Apelina/sangre , Biomarcadores/sangre , Glucemia/metabolismo , Composición Corporal , Colombia , Femenino , Entrenamiento de Intervalos de Alta Intensidad/efectos adversos , Humanos , Insulina/sangre , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Proteínas Musculares/sangre , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Factores de Transcripción/sangre , Resultado del Tratamiento

RESUMEN

IMPORTANCE: Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. OBJECTIVES: To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. MAIN OUTCOMES AND MEASURES: Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline. RESULTS: A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word list recall test and 2.13 (95% CI, -2.29 to -1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (-2.89 vs -2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset. CONCLUSIONS AND RELEVANCE: Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment.

Asunto(s)

Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/genética , Heterocigoto , Presenilina-1/genética , Adulto , Enfermedad de Alzheimer/diagnóstico , Trastornos del Conocimiento/diagnóstico , Estudios de Cohortes , Colombia/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia; the main risk factors are age and several recently identified genes. A major challenge for AD research is the early detection of subjects at risk. The aim of this study is to develop a predictive model using proton magnetic resonance spectroscopy (1H-MRS), a noninvasive technique that evaluates brain chemistry in vivo, for monitoring the clinical outcome of carriers of a fully penetrant mutation that causes AD. METHODS: We studied 75 subjects from the largest multigenerational pedigree in the world (∼5000 people) that segregates a unique form of early-onset Alzheimer's disease (EOAD) caused by a fully penetrant mutation in the Presenilin-1 gene (PSEN1 p.Glu280Ala [E280 A]). Forty-four subjects were carriers of the mutation, and 31 were noncarriers. Seventeen carriers had either mild cognitive impairment (MCI) or early-stage AD (collectively MCI-AD). In right and left parietal white mater and parasagittal parietal gray matter (RPPGM and LPPGM) of the posterior cingulate gyrus and precuneus, we measured levels of the brain metabolites N-acetylaspartate (NAA), inositol (Ins), choline (Cho), and glutamate-glutamine complex (Glx) relative to creatine (Cr) levels (NAA/Cr, Ins/Cr, Cho/Cr, and Glx/Cr, respectively) with two-dimensional 1H-MRS. Using advanced recursive partition analysis and random forest analysis, we built classificatory decision trees for both mutation carrier status and the presence of MCI-AD symptoms, fitting them to 1H-MRS data while controlling for age, educational level, and sex. RESULTS: We found that (1) the combination of LPPGM Cho/Cr<0.165 and RPPGM Glx/Cr>1.54 fully excluded carriers; (2) LPPGM Cho/Cr>0.165, RPPGM Glx/Cr<1.54, and left parietal white mater NAA/Cr>1.16 identified asymptomatic carriers with sensitivity of 97.7% and specificity of 77.4%; and (3) RPPGM NAA/Cr>1.05 defined asymptomatic subjects (independent of carrier status) with sensitivity of 100% and a specificity of 96.6%. CONCLUSIONS: Brain metabolites measured by 1H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation.

Asunto(s)

Enfermedad de Alzheimer/diagnóstico , Encéfalo/metabolismo , Heterocigoto , Mutación , Presenilina-1/genética , Espectroscopía de Protones por Resonancia Magnética/métodos , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Diagnóstico Precoz , Femenino , Humanos , Masculino , Modelos Neurológicos , Curva ROC , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador