HLA alleles and haplotypes in Iran Tabriz Azeris population: genes and languages do not correlate.

Azeri people are at present day mainly living in an area which comprises North (Azerbaijan) and South (Azeri Iran provinces) parts, living the biggest population in Azeri Iran provinces with about 17-20 million people. They were studied HLA-A, -B, -DRB1 and -DQB1 allele and extended haplotype frequencies in unrelated Iranian Tabriz Azeris from a rural area close to Tabriz City. The HLA extended haplotypes with highest frequencies are: 1) HLA- A*24:02-B*35:01-DRB1*11:01-DQB1*03:01, shared with Mediterraneans and southern Russians (Chuvash, which also show Mediterranean characters); and 2) HLA-A*01:02-B*08:01-DRB1*03:01-DQB1*02:01, found also in Chuvash and other Azeri samples from Tabriz. Neí's DA HLA-DRB1 genetic distances, HLA-DRB1 Neighbour-Joining dendrogram and Vista analyses show that population with closest distance is Kurdish, followed by Iranian Gorgan and Southern Russia/ North Caucasus Chuvash; probably these latter groups and Azeris were populating North Mesopotamia/ Caucasus Mts. since prehistoric times. Kurds (in Iraq and Iran) do not speak Turk while Azeris do: they are both genetically close, but they are not genetically close to present day Anatolia (Turkey) Turks who also speak Turk language and show a typical Mediterranean HLA profile. In summary, Azeri population studies show examples that genes and languages do not correlate, contradicting the postulate asserted by others.

Assessment of Neck Grasp as a Screening Tool for Identifying Obstructive Sleep Apnea in Community-Dwelling Older Adults.

BACKGROUND: Inability to encircle the neck by hands (neck grasp) has been proposed as an indicator of obstructive sleep apnea (OSA) that would be useful for recognition of candidates for polysomnography (PSG). We assessed the value of neck grasp for predicting OSA in community-dwelling older adults of Amerindian ancestry. METHODS: Neck grasp was evaluated in individuals aged ≥60 years undergoing PSG. The association between neck grasp and OSA was assessed by logistic regression models adjusted for relevant covariates. Mediation analysis was used to establish the proportion of the effect of the association between neck grasp and OSA, which is mediated by the neck circumference (a well-known OSA biomarker). Receiver operator characteristics curve analysis was used to estimate diagnostic accuracy of neck grasp for predicting OSA. RESULTS: Of 201 individuals undergoing PSG, 167 (83%) had the neck grasp test. The remaining 34 could not perform the test because of different factors. Neck grasp was positive in 127 (76%) cases, and 114 (68%) individuals had OSA (apnea-hypopnea index ≥5). Multivariate logistic regression models disclosed a significant association between neck grasp and OSA. The neck circumference was the single covariate remaining independently significant in these models. Neck grasp was not efficient at predicting OSA (sensitivity: 83.3%, specificity: 39.6%, positive predictive value: 0.75 and negative predictive value: 0.53). The area under the curve disclosed only a moderate predictive capability (61.5%) of neck grasp. CONCLUSION: Results do not support the use of neck grasp as an independent predictor of OSA in the study population.

The association between pineal gland calcification and white matter hyperintensities of presumed vascular origin in older adults. A population-based study.

Pineal gland calcification (PGC) has been associated with low melatonin production, a hormone with anti-oxidant, anti-inflammatory, and neuro-protective effects. Therefore, melatonin deficiency may play a role in the development of cerebral small vessel disease (cSVD), a condition that is partly related to upregulation of oxidative and inflammatory mechanisms leading to endothelial dysfunction, breakdown of the blood-brain barrier, and impaired interstitial fluid drainage. In this study, the association between PGC (a surrogate for melatonin deficiency) and white matter hyperintensities (WMHs) of presumed vascular origin (a biomarker of cSVD) was assessed in Atahualpa cohort individuals aged ≥60 years undergoing head CT and brain MRI. PGC was rated as none-to-mild and moderate-to-severe. WMHs were classified according to the modified Fazekas scale. A logistic regression model was fitted to assess the independent association between moderate-to-severe PGC and WMHs. Inverse probability of exposure weighting was used to estimate the effect of PGC on WMH. Of 373 individuals, 96 (26%) had moderate-to-severe PGC and 86 (23%) had moderate-to-severe WMHs. Moderate-to-severe PGC and WMH were independently associated in a fully-adjusted logistic regression model (OR: 2.21; 95% C.I.: 1.19-4.11; p = 0.012). Inverse probability of exposure weighting showed an estimate for the proportion of moderate-to-severe WMH among those with none-to-mild PGC of 20.5%, and the exposure-effect was 13.2% higher among those with moderate-to-severe PGC (ß: 0.132; 95% C.I: 0.036-0.229; p = 0.007). The association found in this study provides grounds for further evaluation of the role of melatonin deficiency in cSVD development.

Sleep quality correlates with the carotid intima-media thickness in stroke-free community-dwelling adults living in rural Ecuador. The Atahualpa Project.

BACKGROUND/OBJECTIVES: Evidence of an association between sleep disorders and extracranial atherosclerosis is limited and has not been studied in remote rural settings, where living conditions and cardiovascular risk factors are different than in urban centers. We assessed the relationship between the carotid intima-media thickness (cIMT) and sleep quality in stroke-free individuals aged ≥40 years living in rural Ecuador. METHODS: Applying a population-based study design, participants underwent face-to-face interviews using the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality, and sonographic examinations for measurement of the carotid intima-media thickness (cIMT). The association between the cIMT and sleep quality (as the dependent variable) was assessed by means of generalized linear models, adjusted for relevant confounders. RESULTS: The mean age of 561 participants was 60.4 ± 12.6 years (58% women). The mean PSQI was 4.6 ± 2.2 points. Of those, 79 (14%) individuals had an increased cIMT (>1 mm). A model adjusted for demographics showed a significant association between increased cIMT and the PSQI score (ß: 0.602; 95% C.I.: 0.027-1.177; p = 0.040). This relationship was reduced when cardiovascular risk factors were added to the model (ß: 0.514; 95% C.I.: -0.072 - 1.101; p = 0.086). When the model was adjusted for demographics and psychological distress, the association between increased cIMT and the PSQI score became significant (ß: 0.573; 95% C.I.: 0.013-1.133; p = 0.045). In addition, both symptoms of depression (p = 0.032) and anxiety (p < 0.001) remained independently significant. CONCLUSIONS: This study shows an association between increased cIMT and the PSQI score, which is, at least, partly mediated by manifestations of psychological distress.

Intracranial Atherosclerosis And The Earlobe Crease (Frank's Sign). A Population Study / Aterosclerosis Intracraneal Y Pliegue Auricular (Signo De Frank). Estudio Poblacional

ABSTRACT Background: The earlobe crease (ELC) has been linked to coronary artery disease and other vascular conditions, but there is no information on its association with intracranial atherosclerosis. Objective: This study aimed to assess the association between high calcium content in the carotid siphons (as a surrogate of intracranial atherosclerosis) and ELC in community-dwelling adults living in rural Ecuador. Methods: Atahualpa residents aged ≥40 years underwent head CT to estimate calcium content in the carotid siphons, and visual inspection of both earlobes to evaluate the presence of ELC. The association between both variables was assessed by logistic regression models, after adjusting for demographics and cardiovascular risk factors. Results: Of 651 enrolled individuals (mean age: 59.7±12.8 years; 54% women), 225 (35%) had ELC, and 143 (22%) had high calcium content in the carotid siphons. Univariate logistic regression showed a borderline (non-significant) association between high calcium content in the carotid siphons and ELC presence (OR: 1.44; 95% C.I.: 0.99 - 2.12; p=0.057), which disappeared when age (OR: 0.98; 95% C.I.: 0.65 - 1.48; p=0.923) and other covariables (OR: 0.97; 95% C.I.: 0.63 - 1.49; p=0.890) were added to the model. Conclusion: This population study shows no association between high calcium content in the carotid siphons and ELC presence.

RESUMEN Antecedentes: El pliegue auricular se ha relacionado con enfermedad coronaria y otras patologías vasculares, pero no hay información sobre su asociación con aterosclerosis intracraneal. Objetivo: Este estudio tuvo como objetivo evaluar la asociación entre el contenido de calcio en los sifones carotideos (como un sustituto de aterosclerosis intracraneal) y el pliegue auricular en adultos viven en zonas rurales de Ecuador. Métodos: Los residentes de Atahualpa de 40 años o más fueron sometidos a TC de cerebro para estimar el contenido de calcio en los sifones carotideos. Además, ambas orejas fueron examinadas para detectar la presencia de pliegues auriculares. La asociación entre ambas variables se evaluó mediante modelos de regresión logística, ajustados por factores demográficos y de riesgo cardiovascular. Resultados: De 651 individuos enrolados (edad media: 59,7±12,8 años, 54% mujeres), 225 (35%) tuvieron pliegues auriculares y 143 (22%) tuvieron alto contenido de calcio en los sifones carotideos. La regresión logística univariada mostró una asociación limítrofe (no significativa) entre el contenido de calcio en los sifones carotideos y la presencia de pliegue auricular (OR: 1.44, 95%IC: 0.99 - 2.12, p=0.057), que desapareció cuando la edad (OR: 0.98; 95% I.C.: 0,65 - 1,48; p=0,923) y otras covariables (OR: 0,97; 95% I.C.: 0,63 - 1,49; p=0,890) fueron agregadas al modelo estadístico. Conclusión: El presente estudio no mostró asociación entre el contenido de calcio en los sifones carotídeos y la presencia de pliegue auricular.

The association between earlobe crease (Frank's sign) and cognitive performance is related to age. Results from the Atahualpa Project.

BACKGROUND: Earlobe crease (ELC) has been linked to cardiovascular diseases, but information on its association with cognitive decline is limited. We aimed to assess the association between ELC and cognitive performance in community-dwelling adults living in rural Ecuador. METHODS: Of 863 individuals aged ≥40 years enrolled in the Atahualpa Project, 629 (73%) were included. ELC were visually identified by two independent raters, and cognitive performance was measured by the Montreal Cognitive Assessment (MoCA). Using generalized linear and interaction models, adjusted for demographics, cardiovascular risk factors and edentulism, we assessed the association between ELC and cognitive performance, as well as the influence of age in this association. RESULTS: ELC was present in 246 (39%) individuals, and the mean MoCA score in the entire population was 21.9 ± 4.7 points. A generalized linear model showed no relationship between ELC presence and the MoCA score (p = 0.449). In this model, covariates remaining significant were age (p < 0.001), physical activity (p = 0.014) and edentulism (p < 0.001). When participants were stratified according of quartiles of age, the MoCA score did not differ according to the presence or absence of ELC. Weighted exposure-effect models - using ELC and the MoCA score as the exposure and outcome (respectively) - revealed no association between both variables. CONCLUSIONS: The association between ELC and the MoCA score is mainly related to age. These findings might be explained by the high prevalence of ELC and cognitive decline in older adults.

Arterial Stiffness is Independently Associated with Severity of Carotid Siphon Calcifications in Community-Dwelling Older Adults: The Atahualpa Project.

BACKGROUND: Knowledge on the association between arterial stiffness and intracranial atherosclerosis is limited. Here, we aimed to assess whether the aortic pulse wave velocity (PWV)-used as a surrogate of arterial stiffness-might independently predict severity of carotid siphon calcifications (CSCs), used as a marker of atherosclerosis. METHODS: Of 437 Atahualpa residents aged 60 years or older, 300 (69%) underwent head computed tomography (CT) (for CSC assessment), brain magnetic resonance imaging (for identification of neuroimaging signatures of cerebral small vessel disease [SVD]), and aortic PWV determinations (for arterial stiffness estimation). Ordinal logistic regression models were constructed to predict severity of CSC (as the dependent variable) according to levels of aortic PWV after adjusting for demographics, cardiovascular risk factors, and neuroimaging signatures of SVD. RESULTS: Grade 1 CSC were noticed in 120 (40%) subjects, grade 2 in 84 (28%), grade 3 in 73 (24%), and grade 4 in 23 (8%). The mean PWV was 10.4 ± 1.8 m/s, which increased from 9.8 ± 1.3 to 11.1 ± 2.1 m/s in individuals with grades 1 and 4 CSC, respectively (P <.001). The most parsimonious ordinal logistic regression model adjusted for relevant confounders showed a significant association between aortic PWV and severity of CSC. In this model, a change of 1 unit of aortic PWV increased the odds of CSC severity by 1.22 (95% confidence interval 1.07-1.39; P = .004). CONCLUSIONS: The monotonically increased odds of aortic PWV among subjects with different grades of CSC, suggest that aortic PWV may be a marker for identifying candidates for CT screening in the search of CSC.

Enlarged Basal Ganglia Perivascular Spaces are Associated with Pulsatile Components of Blood Pressure.

BACKGROUND/AIMS: Pathogenetic mechanisms involved in enlargement of basal ganglia perivascular spaces (BG-PVSs) are controversial. Here, we assessed whether pulsatile or steady components of blood pressure (BP) are associated with enlarged BG-PVS. METHODS: We evaluated the association between BG-PVS and pulsatile and steady components of BP in Atahualpa residents aged ≥60 years, by the use of regression models and receiver operator characteristics (ROC) curve analysis, after taking into account the effect of demographics, cardiovascular risk factors, and other signatures of cerebral small vessel disease (SVD). RESULTS: Of 437 candidates, 363 (83%) were included. MRI showed >10 enlarged BG-PVS in 103 (28%) subjects. In univariate analysis, the association between enlarged BG-PVS and systolic pressure (SP) and pulse pressure (PP) were highly significant, while the association with diastolic pressure (DP) was not. ROC curve analysis showed a higher area under the curve for PP than for DP (p < 0.05). The area under the curve for SP was also higher than that of DP, but not significantly better due to overlapping 95% CI. CONCLUSION: Enlarged BG-PVS are associated with pulsatile components of BP, although some of the effect is taken away by the strong interaction between BG-PVS and other signatures of SVD.

Symptoms of Neurotoxicity among Carpenters Living in Rural Ecuador: A Population-based Study (The Atahualpa Project).

BACKGROUND: There is no information on the prevalence of symptoms related to neurotoxicity among carpenters working in underserved populations. To assess the magnitude of the problem, we conducted a population-based study in Atahualpa, a rural Ecuadorian village, where most men work as carpenters under poor safety conditions. METHODS: All men aged 40-75 years living in Atahualpa were identified during a door-to-door survey and evaluated with a general demographic questionnaire, the Q16 questionnaire, the depression axis of the Depression Anxiety Stress Scale-21, and the Montreal Cognitive Assessment (MoCA). RESULTS: Among 230 participants, 63% were carpenters. Seventy participants (30%) had a positive Q16 questionnaire (≥6 points), which suggested neurotoxicity. In a logistic regression model adjusted for age, education, alcohol intake, symptoms of depression, and MoCA score, the proportion of Q16 positive persons was 39.1% for carpenters and 15.9% for noncarpenters (odds ratio: 3.53, 95% confidence interval: 1.75-7.15, P < 0.0001). In a generalized linear model, adjusted mean scores in the Q16 questionnaire were 4.9 for carpenters and 3.6 for noncarpenters (ß: 1.285, standard error: 0.347, P < 0.0001). There was no correlation between scores in the Q16 questionnaire and the MoCA (Pearson correlation coefficient = -0.02), and the only significant covariate in the multivariate linear model was age, with every 10 years of age difference contributing 0.64 points in the Q16 questionnaire. CONCLUSION: This study shows a high prevalence of symptoms associated with neurotoxicity among carpenters after adjusting for a number of confounders. Long-term exposure to toxic solvents is the most likely explanation to this finding.

The Role of Brachial Pulse Pressure as an Indicator of Intracranial Atherosclerosis: The Atahualpa Project.

INTRODUCTION: Carotid siphon calcifications (CSC) are an important imaging marker of systemic atherosclerosis. Routine assessment of asymptomatic CSC may allow the implementation of intervention strategies before catastrophic cerebrovascular events occur. AIM: To assess whether brachial PP determinations might independently predicts the presence and severity of CSC in community-dwelling adults. METHODS: All Atahualpa residents aged ≥40 years were invited for the practice of a non-enhanced CT scan of the head, and those who signed the informed consent and had no contraindications for this exam were enrolled. The brachial PP was calculated by subtracting the mean diastolic pressure from the mean systolic pressure obtained from three different readings with individuals in the sitting position. RESULTS: Of 830 eligible candidates, 663 (80%) were included. The mean brachial PP was 56.4 ± 19.9 mmHg; 182 persons (27.4%) had PP levels >65 mmHg. CT revealed Grade 1 CSC in 356 (54%), Grade 2 in 141 (21%), Grade 3 in 128 (19%), and Grade 4 in 38 (6%) subjects. Predictive margins of PP (delta method) were significantly lower in individuals with Grade 1 CSC than in the other groups. In the best adjusted linear model, PP levels increased up to 11.7 mmHg as the severity of CSC increased (ß 11.71; 95% C.I. 5.36-18.08: p < 0.001). CONCLUSION: This study provides evidence on the relationship between brachial PP levels and intracranial atherosclerosis. Calculation of the PP may be used for detecting candidates for CT screening, reducing costs during population-based surveys, particularly in remote areas.

Atahualpa, una población rural ideal para la práctica de estudios epidemiológicos / Atahualpa, an optimal rural setting for the practice of epidemiological studies

RESUMEN Atahualpa es una población rural situada en el litoral Ecuatoriano, que cumple una serie de requisitos como para ser considerada ideal para la práctica de estudios epidemiológicos. Entre estos destacan el hecho de ser una población aislada, con muy bajos índices de migración y bastante homogénea en lo que respecta a raza, costumbres, estilos de vida y alimentación, la cual es rica en pescado oleoso. Los habitantes son nativos Ecuatorianos con escasa evidencia de mestizaje. La mayoría de los hombres son carpinteros y las mujeres cumplen quehaceres del hogar. Estas coincidencias reducen el riesgo de factores confusores que pueden comprometer la veracidad de los datos al momento del análisis. Sin embargo, esta homogeneidad podría condicionar que los datos obtenidos en este pueblo no sean extrapolables a otras comunidades de la región. Es necesario hacer réplicas del Proyecto Atahualpa en poblados vecinos (utilizando protocolos similares), con la finalidad de valorar la generalización de los datos obtenidos en esta población.

ABSTRACT Atahualpa is a rural village located in coastal Ecuador that achieves a number of requisites to be considered as an optimal setting for the practice of epidemiological studies. Atahualpa is an isolated village with a very low index of migration rate. Inhabitants are fairly homogeneous regarding race, lifestyles and diet, which is rich in oily fish. From the racial point of view, inhabitants are Ecuadorian natives with little evidence of cross-breading. Most men are artisan carpenters and most women are homemakers. These coincidences reduce the risk of the presence of unexpected confounders at the time of data analyses. However, this may also cause that data obtained might not be extrapolated to other regions. The practice of studies in neighboring villages, using similar protocols, is needed to validate generality of data obtained in Atahualpa.

El Proyecto Atahualpa: protocolo, definiciones operacionales y diseño inicial / The Atahualpa Project: protocol, operational definitions, and initial study design

RESUMEN Las enfermedades no transmisibles constituyen las nuevas epidemias de salud de países en vías de desarrollo. Esto se debe, en gran parte, al aumento en la expectativa de vida y a los cambios en estilo de vida y hábitos dietéticos de sus habitantes. El Proyecto Atahualpa fue diseñado como un estudio de múltiples etapas, de corte longitudinal, dirigido a reducir el aumento de la carga de estas estas enfermedades en zonas rurales del Ecuador. La primera etapa consistió en un estudio de 3 fases, dirigido a conocer información sobre los aspectos demográficos y los factores de riesgo cardiovasculares en los residentes de Atahualpa ≥40 años, así como estimar tasas de prevalencia de enfermedad cerebrovascular y cardiopatía isquémica. Durante la Fase I, los participantes fueron encuestados con cuestionarios estandarizados dirigidos a evaluar la salud cardiovascular y a determinar la presencia de individuos sospechosos de tener una enfermedad cerebrovascular o cardiopatía isquémica. En la Fase II, neurólogos y cardiólogos examinaron individuos sospechosos y una muestra aleatoria de individuos no-sospechosos, para determinar la prevalencia de dichas enfermedades. En la Fase III, los pacientes confirmados fueron sometidos a exámenes complementarios dirigidos a establecer diagnóstico etiológico. La implementación de estrategias de salud pública dirigidas a mejorar el estado de salud cardiovascular en una población, debe ser basada en información regional. Los estudios epidemiológicos, tales como el Proyecto Atahualpa, son costo-efectivos para mejorar el estado de salud cardiovascular de poblaciones rurales de América Latina, al incrementar el conocimiento de las necesidades particulares de cada población.

ABSTRACT Non-communicable diseases are the new health epidemics in developing countries due to increased life expectancy, and changes in lifestyle and dietary habits of the population. The Atahualpa Project was designed as a multi-step population-based cohort study designed to reduce the increasing burden of these conditions in rural Ecuador. The first step of the study followed a 3-Phase design, aimed to get information on demographics and cardiovascular risk factors of Atahualpa residents aged ≥40 years, as well as to assess the prevalence of stroke and ischemic heart disease. During Phase I, participants were screened with standardized questionnaires to evaluate their cardiovascular health and to identify those with suspected stroke or ischemic heart disease. In Phase II, neurologists and cardiologists examined suspected cases of stroke or ischemic heart disease, as well as a random sample of matched negative individuals, to assess prevalence of these conditions. In Phase III, patients with diagnosis of stroke and ischemic heart disease underwent complementary tests for achieving more specific diagnosis. Implementation of public health strategies directed to improve the cardiovascular health status of a given population must be based on studies evaluating specific risk factors at regional levels. Epidemiologic surveys such as the Atahualpa Project may prove cost-effective for improving the cardiovascular health status of people living in Latin American rural villages by increasing the knowledge on the particular needs of these populations.

Salud cardiovascular en habitantes de Atahualpa: características y correlatos / Cardiovascular health status in Atahualpa residents: characteristics and correlates

RESUMEN Las enfermedades vasculares son consideradas como las nuevas epidemias de salud en América Latina debido al aumento en la expectativa de vida y a cambios en el estilo de vida de sus habitantes. El conocimiento del estado de salud cardiovascular (SCV) de estas poblaciones es mandatorio para implementar estrategias costo-efectivas dirigidas a reducir la prevalencia de estas enfermedades en la región. En el Proyecto Atahualpa se ha valorado el estado de SCV de los participantes, utilizando los marcadores de salud propuestos por la Asociación Americana del Corazón. El estudio basal incluyó 616 sujetos libres de enfermedad cerebrovascular y cardiopatía isquémica, con edad ≥40 años. De estos, el 2.1% tuvieron un estado de salud ideal, el 28.1% intermedio y el 69.8% pobre. Los peores marcadores incluyeron presión arterial, glucosa en ayunas e índice de masa corporal. La posibilidad de tener un estado de SCV pobre estuvo aumentada en sujetos ≥60 años y en aquellos con escolaridad primaria. Luego, comparamos el estado de SCV de nuestra población con la de hispanos enrolados en el NOMAS, y encontramos que los residentes de Atahualpa tuvieron mejores marcadores de salud, con excepción de los niveles de glucosa en ayunas. La posibilidad de tener 5-7 marcadores en rango ideal fue más elevada en los residentes de Atahualpa, independientemente de la edad. También realizamos un estudio para valorar la SCV dependiendo del aislamiento social y encontramos que el vivir solo se asoció con un peor estado de SCV. Otros estudios mostraron relación entre ciertas patologías del sueño y un peor estado de SCV. Finalmente, hemos empezado el programa "conoce tus números", el cual sumado a charlas comunitarias, se encuentra dirigido a mejorar la SCV de los residentes de Atahualpa y reducir la incidencia de eventos vasculares en la región.

ABSTRACT Stroke and cardiovascular diseases will be the next epidemics in Latin America due to changes in lifestyle and increased life expectancy. Knowledge of cardiovascular health (CVH) status of the population is mandatory to implement cost-effective strategies directed to reduce the burden of vascular diseases in the region. In the Atahualpa Project, we assessed the CVH status of participants using the metrics proposed by the American Heart Association. The basal study included 616 subjects free of stroke and ischemic heart disease aged ≥40 years. Of these, 2.1% had ideal, 28.1% had intermediate and 69.8% had poor CVH status. Poorest metrics were blood pressure, fasting glucose, and BMI. The odds for having a poor CVH status were increased in persons aged ≥ 60 years and in those with only primary school education. Then, we compared our results with the Hispanic population of the Northern Manhattan Stroke Study (NOMAS), and found that Atahualpa residents had significantly better metrics than those enrolled in the NOMAS, with the exception of fasting glucose levels. Likewise, the odds for having 5 to 7 ideal metrics were also better in Atahualpa residents, irrespective of age. We also conducted a case-control study to assess the CVH status of Atahualpa residents according to their living arrangements, and found that social isolation was associated with a worse CVH status in this population. A couple of studies showed correlation between some sleep related disorders and poor CVH status. We have also started an ongoing program called "known your numbers", which, together with community talks, is directed to improve the CVH status and to reduce the burden of vascular diseases in the region.

Sub-estudio de neuroimagen del Proyecto Atahualpa / Neuroimaging substudy of the Atahualpa Project

RESUMEN Como parte del Proyecto Atahualpa se diseñó el sub-estudio de neuroimagen, el cual incluye la práctica de IRM y angio-resonancias a toda la población ≥60 años, así como a participantes con padecimientos que ameriten estos exámenes. De igual manera, toda la población de ≥20 años ha sido invitada para la práctica de TC de cerebro. Las IRMs y angio-resonancias han sido realizadas en un equipo marca Philips, modelo Intera, de 1.5 Tesla, y las TC en un equipo helicoidal marca Philips, modelo Brilliance 64, siguiendo protocolos de investigación internacionalmente establecidos. Todos los exámenes han sido interpretados de manera independiente por un neurólogo y un neuroradiólogo. Hasta el momento, la mayoría de lecturas han tenido coeficientes de correlación (kappa) satisfactorio (excelente o muy bueno) y las discrepancias se han solucionado por consenso. Los estudios de IRM se han enfocado en estimación de atrofia cortical global, atrofia parietal posterior, atrofia de núcleo caudado, índice de Evans, atrofia de hipocampo, marcadores de enfermedad de pequeño vaso cerebral, y en la búsqueda de lesiones compatibles con infartos y hemorragias cerebrales. Utilizando angio-resonancia hemos valorado la presencia de estenosis de arterias intracraneales, dolicoectasia basilar y configuración del polígono de Willis. En TC, nos hemos enfocado en el diagnóstico de calcificaciones cisticercosas, en la presencia y severidad de las calcificaciones de la glándula pineal, en las variaciones en grosor, heterogeneidad de los huesos del diploe, en la atrofia de cerebelo, y en la estimación del grado de calcificación de los sifones carotideos. En el presente artículos se describen los protocolos básicos utilizados para la valoración de cada una de las lesiones of interés mencionadas previamente.

ABSTRACT The Atahualpa Project includes a Neuroimaging sub-study, which consists in the practice of MRIs and MRAs to all participants aged ≥60 years, as well as those presenting with specific neurological complains. Likewise, all participants aged ≥20 years have been invited for the practice of a head CT. MRIs and MRAs have been performed with the use of a Philips Intera 1.5T MRI machine, and TCs with the use of a Philips Brilliance 64 CT scanner, following established protocols. All exams have been independently reviewed by a neurologist and a neuroradiologist, with adequate kappa coefficients for inter-rater agreement. MRIs studies have been focused on the evaluation of global cortical atrophy, posterior parietal atrophy, bicaudate index, Evans index, hippocampal atrophy, signatures of cerebral small vessel disease, and lesions consistent with ischemic or hemorrhagic strokes. By the use of MRI, we have assessed the prevalence of intracranial artery stenosis, intracranial dolichoectasia and variations in the configuration of the circle of Willis. Using CT, we have focused on the diagnosis of neurocysticercosis, pineal gland calcifications, as well as in variations and characteristics of skull bones, cerebellar atrophy, and severity of carotid siphon calcifications. In the present study, we focused on the description of basic protocols used for assessment of previously mentioned lesions of interest.

Búsqueda de substitutos para estudios de neuroimagen con propósitos de investigación: Experiencia del Proyecto Atahualpa / The search of surrogates for neuroimaging studies for research purposes: The Atahualpa Project Experience

RESUMEN El diagnóstico de muchas de las enfermedades neurológicas no transmisibles requiere de la práctica de una resonancia magnética, la cual no se encuentra disponible en regiones rurales o remotas. Es importante realizar esfuerzos destinados a encontrar pruebas diagnósticas portátiles que sirvan como tamizaje para la identificación de personas que necesitan ser sometidas a una IRM. Como parte del Proyecto Atahualpa, hemos invitado a todos los participantes ≥60 años para la práctica de una IRM de cerebro y aproximadamente el 80% de las personas han aceptado el procedimiento. Por lo tanto, tenemos la oportunidad única de probar la validez de pruebas no-invasivas que puedan ser utilizadas como substitutos de resonancia para identificar candidatos a hacerse dicho examen. Hasta la fecha, hemos estudiado el valor del índice tobillo-brazo, la confiabilidad de la relación neutrófilos-linfocitos, la exactitud de la presencia de retinopatía hipertensiva y el valor del Doppler transcraneal para la detección de personas con enfermedad de pequeño vaso cerebral. Los individuos con índice tobillo-brazo anormal tiene 4 veces más riesgo de tener un infarto lacunar silente que aquellos con índice normal. Una relación neutrófilos-linfocitos elevada es pobremente sensitiva pero altamente específica para detectar personas con por lo menos un marcador de imagen de enfermedad de pequeño vaso. Los individuos con retinopatía hipertensiva Grados 2-3 tienen casi 4 veces más riesgo de tener hiperintensidades de sustancia blanca que aquellos con retinopatía Grado 1 o sin retinopatía. Finalmente, la correlación del índice de pulsatilidad de las arterias intracraneales para detectar marcadores de enfermedad de pequeño vaso es pobre. Seguimos en la búsqueda de una prueba económica y confiable que permita la identificación de sujetos aparentemente sanos, con riesgo de desarrollar eventos cerebrovasculares catastróficos.

ABSTRACT Diagnosis of many non-communicable neurological diseases require the use of MRI, which is not readily available in remote rural populations. Efforts should be directed to find portable screening diagnostic tools that may help identify candidates for MRI screening. In the Atahualpa Project, all participants aged ≥60 years have been invited for the practice of MRI, and about 80% of them have underwent the procedure. Therefore, we have the unique opportunity to test the accuracy of non-invasive exams to be used as surrogates to MRI for identifying candidates for the practice of this exam. To date, we have assessed the value of the ankle-brachial index ABI), the reliability of the neutrophil-to-lymphocyte ratio (NLR), the accuracy of hypertensive retinopathy, and the value of transcranial Doppler (TCD) to detect individuals with cerebral small vessel disease. Individuals with an abnormal ABI have 4 times de odds of having a silent lacunar infarct than those with a normal ABI. A high NLR has a poor sensitivity but is highly specific for detecting persons with at least one imaging signature of small vessel disease. Individuals with hypertensive retinopathy Grades 2-3 are almost four times more likely to have moderate-to-severe white matter hyperintensities than those with no- or only Grade 1 retinopathy. Finally, the correlation between the pulsatility indexes of major cerebral arteries with imaging markers of small vessel disease, as assessed by TCD, was poor. We are still in the search of some non-expensive and readily available biomarker that allow the identification of apparently healthy persons at risk of suffering a catastrophic cerebrovascular event.

Trastornos de sueño en residentes de Atahualpa / Sleep disorders in Atahualpa residents

RESUMEN Es probable que los problemas de salud relacionados con los trastornos del sueño se encuentren en aumento en las zonas rurales de América Latina, en parte relacionados con los cambios en el estilo de vida, el trabajo con turnos nocturnos y otros factores. Sin embargo, poco se sabe sobre la prevalencia de estas condiciones en lugares rurales remotos. En el Proyecto Atahualpa, hemos investigado los trastornos del sueño utilizando instrumentos de campo estandarizados asociados con tecnología sofisticada como la polisomnografía. Una mala calidad del sueño se ha asociado con fragilidad y con la presencia de marcadores de neuroimagen de enfermedad de vasos cerebrales y atrofia cortical global. Por el contrario, la ingesta dietética de pescado oleoso se asoció con una mejor calidad del sueño. También se ha investigado la prevalencia y algunos correlatos del síndrome de las piernas inquietas (enfermedad de Willis-Ekbom) y se encontró una prevalencia relativamente superior a la descrita en la mayoría de las regiones tropicales, así como la asociación de esta afección con el estrés psicológico. Finalmente, un informe preliminar muestra una elevada prevalencia de apnea obstructiva moderada a severa en los residentes de Atahualpa de ≥60 años (27%) y su correlación con daño subcortical difuso de origen vascular. Se necesitan más estudios para comprender mejor las consecuencias de los síntomas relacionados con el sueño en dichas poblaciones.

ABSTRACT Health problems related to sleep disorders are likely on the rise in rural areas of Latin America, partly related to changes in life style, shift work, and other factors. However, little is known on the burden of these conditions in remote rural settings. In the Atahualpa Project, we have investigated sleep disorders using standardized field instruments associated with sophisticated technology such as polysomnography. A poor sleep quality has been associated with frailty and with the presence of neuroimaging markers of cerebral small vessel disease and global cortical atrophy. On the contrary, dietary intake of oily fish was associated with a better sleep quality. We have also investigated the prevalence and some correlates of the restless legs syndrome (Willis-Ekbom disease), and found a prevalence relatively higher than that described in most other tropical regions, as well as the association of this condition with psychological stress. Finally, a preliminary report shows a high prevalence of moderate-to-severe obstructive sleep apnea in Atahualpa residents aged ≥60 years (27%) and its correlation with diffuse subcortical damage of vascular origin. Further studies are needed to better understand consequences of sleep-related symptoms in underserved populations.

Alcohol: consumo, consecuencias y complicaciones neurológicas. Resultados del Proyecto Atahualpa / Alcohol: intake, consequences and neurological complications. Results from the Atahualpa Project

RESUMEN La información sobre la prevalencia y consecuencias de la ingesta de alcohol en las comunidades rurales de América Latina es escasa. Este estudio tiene como objetivo evaluar la magnitud de la ingesta de alcohol en Atahualpa, así como sus consecuencias y la prevalencia de complicaciones neurológicas. Se entrevistó a los residentes de sexo masculino mayores de 40 años (n=277) con un cuestionario estructurado diseñado para evaluar la prevalencia, los patrones de consumo y las consecuencias de la ingesta crónica de alcohol. La mayoría eran bebedores actuales y el 40% empezaron a beber por debajo de la edad legal (18 años). El consumo semanal de alcohol fue admitido por el 81% de las personas, el 58% refirió consecuencias físicas relacionadas con la ingesta de alcohol, el 59% tuvo consecuencias sociales y el 51% reconoció la ingesta de alcohol como una carga económica. Las personas que comenzaron a beber por debajo de la edad legal estuvieron más a menudo involucradas en el consumo excesivo y consumieron más alcohol que aquellos que comenzaron a tomar después de los 18 años. La relación entre ingesta de alcohol y degeneración alcohólica cerebelosa se evaluó mediante el uso de la escala BARS, con el 14,6% de individuos con degeneración alcohólica cerebelosa clínicamente relevante. Los modelos predictivos mostraron relaciones significativas entre los márgenes de puntuación de BARS y los años de consumo y la cantidad de ingesta de alcohol. Nuestro estudio también proporcionó pruebas sólidas que favorecen un efecto independiente y sinérgico de la edad y los años de consumo de alcohol en la relación entre degeneración alcohólica cerebelosa y deterioro cognitivo. Este estudio muestra una alta prevalencia de consumo crónico de alcohol en los hombres que habitan en la comunidad de Atahualpa.

ABSTRACT Information about the burden and consequences of alcohol intake in rural communities of Latin America is scarce. This study aims to assess the magnitude of alcohol intake in Atahualpa as well as its consequences and prevalence of neurological complications. Male residents aged ≥40 years (n=277) were interviewed with a structured questionnaire designed to evaluate prevalence, drinking patterns and consequences of chronic alcohol intake. Most of them were current drinkers and 40% started drinking below the legal age (18 years). Weekly binge drinking were admitted by 81% individuals, 58% referred physical consequences related to alcohol intake, 59% had social consequences, and 51% recognized alcohol intake as a major economic burden. Individuals who started drinking below the legal age were more often involved in binge drinking and consumed more alcohol than those aged ≥18 years at first regular drink. The relationship between alcohol intake and alcoholic cerebellar degeneration was evaluated by the use of the BARS scale, with 14.6% of individuals having clinically relevant alcoholic cerebellar degeneration. Predictive models showed significant relationships between BARS score margins and years of drinking and the amount of alcohol intake. Our study also provided robust evidence favoring an independent and synergistic effect of age and years of drinking in the relationship between ACD and cognitive decline. This study shows a high prevalence of chronic alcohol intake in community-dwelling men living in Atahualpa.

Enfermedad cerebrovascular en Atahualpa: prevalencia e incidencia / Cerebrovascular disease in Atahualpa: prevalence and incidence

RESUMEN El impacto de la enfermedad cerebrovascular (ECV) está en aumento en las regiones rurales de América del Sur. Evaluamos la prevalencia, subtipos y mecanismos patogénicos de la ECV en Atahualpa. En un estudio de tres fases, los casos sospechosos fueron detectados por una encuesta puerta-a-puerta. Luego, los neurólogos evaluaron casos sospechosos y seleccionaron al azar personas negativas, y los pacientes confirmados se sometieron a exámenes. Se encontraron 20 pacientes con ECV entre 642 personas ≥40 años. La prevalencia fue 31,15‰ y aumentó con la edad. La arteriolopatía hipertensiva fue el mecanismo más probable de los ECV (55% de los pacientes). En ningún caso se encontraron lesiones ateroscleróticas extracraneales o fuentes cardíacas de embolia. La comparación de nuestros hallazgos con una encuesta anterior realizada en Atahualpa mostró un aumento alarmante en la prevalencia de ECV (14,08‰ en 2003 a 31,15‰ en 2012, p=0,03). Posteriormente, se realizó un estudio de incidencia. Para ello, todos los eventos nuevos ocurridos a lo largo de cuatro años se identificaron. De 807 individuos sin ECV ingresados prospectivamente en el Proyecto Atahualpa, el seguimiento se logró en 718 (89%), contribuyendo con 2.499 años de seguimiento (promedio de 3,48 ± 0,95 años). La incidencia de ECV fue de 2,97 por 100 años-persona de seguimiento (95% C.I.: 1,73-4,2), que aumentó a 4,77 (95% C.I.: 1,61-14,1) cuando se consideraron las personas mayores de 57 años. Los modelos de regresión de Poisson, ajustados para los factores de confusión relevantes, mostraron que la presión arterial alta (IRR: 5,24; 95% C.I.: 2,55-7,93) y el edentulismo (IRR: 5,06; 95% C.I.: 2,28-7,85). La incidencia de ECV en Atahualpa es comparable a la reportada en el mundo desarrollado. Además de la edad y la presión arterial alta, el edentulismo es un factor importante que predice independientemente los ECV.

ABSTRACT Stroke burden is on the rise in rural regions of South America. We evaluated prevalence, pattern of subtypes and pathogenetic mechanisms underlying stroke in Atahualpa. In a three-phase epidemiologic study, suspected cases were detected by a door-to-door survey. Then, neurologists evaluated suspected cases and randomly selected negative persons, and confirmed patients underwent complementary exams. We found 20 stroke patients among 642 persons aged ≥ 40 years. Stroke prevalence was 31.15‰ that increased with age. Hypertensive arteriolopathy was the most likely mechanism underlying strokes (55% patients). Extracranial atherosclerotic lesions or cardiac sources of emboli were not found in any case. Comparison of our findings with a previous survey performed in the same village showed an alarming increase in stroke prevalence (from 14.08‰ in 2003 to 31.15‰ in 2012, p=0.03). Thereafter, we conducted an incidence study. For this, first-ever strokes occurring over four years were identified from yearly door-to-door surveys and other overlapping sources. Of 807 stroke-free individuals prospectively enrolled in the Atahualpa Project, follow-up was achieved in 718 (89%), contributing 2,499 years of follow-up (average 3.48±0.95 years). Stroke incidence rate was 2.97 per 100 person-years of follow-up (95% C.I.: 1.73-4.2), which increased to 4.77 (95% C.I.: 1.61-14.1) when only persons aged ≥57 years were considered. Poisson regression models, adjusted for relevant confounders, showed that high blood pressure (IRR: 5.24; 95% C.I.: 2.55-7.93) and severe edentulism (IRR: 5.06; 95% C.I.: 2.28-7.85) were the factors independently increasing stroke incidence. Stroke incidence in Atahualpa is comparable to that reported from the developed world. Besides age and high blood pressure, severe edentulism is a major factor independently predicting incident strokes.