Publicación Oficial de la Sociedad Ecuatoriana de Neurología, de la Liga Ecuatoriana Contra la Epilepsia y de la Sociedad Iberoamericana de Enfermedad Cerebrovascular

estudio poblacional

 

Limited value of blood pressure levels in predicting white matter hyperintensities progression among community dwelling older adults living in a rural setting. Utilidad limitada de los niveles de presión arterial como predictor de progresión de hiperintensidades de sustancia blanca en adultos mayores que viven en un entorno rural

Introduction: This study aims to assess the impact of blood pressure (BP) on progression of white matter hyperintensities (WMH) of presumed vascular origin in community-dwelling older adults living in rural Ecuador.

Methods: Atahualpa residents aged ≥60 years receiving baseline and follow-up brain MRIs after a median of 6.5 years were included. Multilevel logistic regression models, which accounted for WMH severity at baseline, were fitted to assess the risk of WMH progression according to BP levels and other covariates.

Results: Analysis included 263 participants. WMH progression increased 3.45 times (95% C.I.: 1.94 – 4.96) among non-hypertensive individuals but 6.15 times (95% C.I.: 3.18 – 9.12) among those with arterial hypertension. However, overlapping of confidence intervals make such difference non-significant. Likewise, no differences in WMH progression were noticed when steady and pulsatile components of BP were used as independent variables.

Conclusions: High BP is not an independent predictor of WMH progression in the study population. 

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The association between pineal gland calcification and intracranial atherosclerotic disease in older adults. Asociación entre calcificaciones de la glándula pineal y enfermedad aterosclerótica intracraneal en adultos mayores

Background: This study assesses whether pineal gland calcification (PGC) – a surrogate for reduced endogenous melatonin production – is associated with significant stenosis of large intracranial arteries – a biomarker of intracranial atherosclerotic disease (ICAD). 

Methods: Individuals aged ≥60 years enrolled in the Three Villages Study received head CT to assess PGC and MRA to estimate stenosis of large intracranial arteries. Multivariate logistic regression models were fitted to assess the association between PGC and ICAD, after adjusting for relevant confounders. Inverse probability of exposure weighting was used to estimate the effect of PGC on ICAD. 

Results: A total of 581 individuals were enrolled. PGC and ICAD were associated in a fully-adjusted logistic regression model (p=0.032). Inverse probability of exposure weighting showed an estimate for the proportion of ICAD among those without PGC of 3.7% and the adjusted-effect coefficient was 5.7% higher among those with PGC (p=0.031). 

Conclusions: PGC is associated with ICAD. Study results provide grounds for evaluating the role of melatonin deficiency in ICAD progression. 

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Arterial Stiffness Is Not Independently Associated With Nighttime Sleep Duration In Community-Dwelling Older Adults. Results From The Atahualpa Project. La Rigidez Arterial no se Encuentra Asociada con la Duración del Sueño Nocturno en Adultos Añosos Que Viven en la Comunidad. Resultados del Proyecto Atahualpa.

Objectives: We aimed to assess the association between arterial stiffness and nighttime sleep duration in community-dwelling older adults living in rural Ecuador.

Methods: Aortic pulse wave velocity (PWV) determinations were used to assess arterial stiffness. Nighttime sleep duration was assessed by a single question. A generalized linear model—adjusted for demographics, cardiovascular risk factors and psychological distress—was fitted to assess the independent association between the aortic PWV and nighttime sleep duration (dependent variable).

Results: A total of 303 individuals were enrolled. Univariate analysis showed a significant association between the aortic PWV and long sleep duration (p=0.034), which vanished in a multivariate linear model (p=0.524). The single covariable remaining significant was anxiety (p=0.013).

Conclusion: Lack of independent association between arterial stiffness and nighttime sleep duration might be more likely related to lack of reliability of evaluation of sleep duration by means of a single question.

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

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 communitydwelling 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.

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El Posicionamiento Elevado de Cabeza y Cuerpo Podrían Afectar la Autorregulación Cerebral Dinámica en Pacientes con Enfermedad Silente de Pequeño Vaso Cerebral. Protocolo y Definiciones Operacionales. Head-Up And Body Positioning Might Impair Dynamic Cerebral Autoregulation In Patients With Silent Cerebral Small Vessel Disease. Protocol And Operational Definitions.

Background: Cerebral autoregulation (CA) is the ability of intracranial vessels to maintain a constant cerebral blood flow (CBF) during changes of cerebral perfusion pressure (CPP) related to fluctuations in blood pressure, postural changes or increased metabolic demands. It has been suggested that individuals with silent cerebral small vessel disease (SVD) may have impaired CA, but information is inconclusive. We describe the protocol of a study aimed to assess the association between white matter hyperintensities (WMH) of presumed vascular origin and poor dynamic CA, and to determine the effects of head-up and body positioning in patients with this condition. Methods: Using a case-control study design, we will assess the relationship between severity of WMH and dynamic CA, measured by continuous transcranial Doppler assessment of CBF velocities in the middle cerebral arteries (MCAs) combined with beat-to-beat blood pressure monitoring. Dynamic CA will be analyzed by calculating the mean flow index as the ratio of median arterial pressure and mean flow velocities of the MCAs. Participants will be categorized as case-patients if the MRI shows moderate-to-severe WMH. For every case-patient, an age- and sex-matched healthy individual with no neuroimaging evidence of SVD will be selected as a control. Comment: This study will assess whether head-up and body positioning impairs dynamic CA in the setting of diffuse subcortical damage related to SVD, providing further evidence on the importance of CPP in maintaining the CBF. If positive, the study will provide evidence favoring the stop of aggressive hypertensive therapy or interventions promoting orthostatic hypotension to reduce the risk of further ischemic brain damage in these cases.

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Atahualpa, Una Población Rural Ideal Para la Práctica de Estudios Epidemiológicos. Atahualpa, An Optimal Rural Setting For The Practice Of Epidemiological Studies

Atahualpa is a rural village located in coastal Ecuador that achieve 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.

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El Proyecto Atahualpa, Protocolo, Definiciones Operacionales y Diseño Inicial. The Atahualpa Project: Protocol, Operational Definitions, And Initial Study Design

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.

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Salud Cardiovascular en Habitantes de Atahualpa: Características y Correlatos. Cardiovascular Health Status In Atahualpa Residents: Characteristics And Correlates

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.

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Sub-estudio de Neuroimagen del Proyecto Atahualpa. Neuroimaging Substudy Of The Atahualpa Project

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.

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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

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.

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Trastornos de Sueño en Residentes de Atahualpa. Sleep Disorders In Atahualpa Residents.

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.

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Alcohol: Consumo, Consecuencias y Complicaciones Neurológicas. Resultados del Proyecto Atahualpa. Alcohol: Intake, Consequences and Neurological Complications. Results From The Atahualpa Project.

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.

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Enfermedad Cerebrovascular en Atahualpa: Prevalencia e Incidencia. Cerebrovascular Disease In Atahualpa: Prevalence And Incidence

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.

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Deterioro Cognitivo: Prevalencia y Correlatos en una Comunidad Rural Ecuatoriana. Lecciones del Proyecto Atahualpa. Cognitive Decline: Prevalence And Correlates In A Rural Ecuadorian Community. Lessons From The Atahualpa Project.

Assessment of cognitive impairment in rural areas of developing countries is complicated by illiteracy and cross-cultural factors. The Montreal Cognitive Assessment (MoCA) was used to estimate cognitive performance in individuals enrolled in the Atahualpa Project. Some problems were noticed with the use of this test, including issues related to naming animals, as well as the need to adjust a different cutoff for diagnosing mild cognitive decline than that used in highly educated individuals living in developed countries. After correlating MoCA scores with neuroimaging signatures of cortical and subcortical atrophy, a cutoff of 19-20 points would better define cognitive impaired individuals in rural areas. We also noticed that severe edentulism as well as psychological distress were associated with poor cognitive performance in older adults living in Atahualpa. In contrast, our study showed a linear, and dose-dependent, direct relationship between dietary oily fish intake and cognitive performance. We also aimed to assess the independent contribution and the interaction of age, the stroke itself and diffuse subcortical damage in the poor cognitive performance observed in patients with stroke, and noticed that interaction of age and diffuse subcortical damage are major determinants for poor cognitive performance among stroke patients. The total cerebral small vessel disease score can be used as a reliable predictor of poor cognitive performance, although its predictive power is not better than that of isolated neuroimaging signatures of cerebral small vessel disease. Finally, we noticed an inverse relationship between calcium content in the carotid siphon – used as a surrogate of intracranial atherosclerosis – and cognitive performance in our population.

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Estudio Poblacional de Prevalencia de Cisticercosis Porcina en Atahualpa, Ecuador. Metodología y Definiciones Operacionales. Population-Based Study Of Porcine Cysticercosis Prevalence In Atahualpa, Ecuador. Methodology And Operational Definitions.

Objective: To assess sero-prevalence of porcine cysticercosis in Atahualpa, a rural Ecuadorian village endemic for human neurocysticercosis.

Design: We aim to collect at least 600 blood samples of local pigs, to quantify the number of positive bands in the EITB, and to estimate crude prevalence rates of porcine cysticercosis in the village. Sampling will only include pigs older than 2 months of age. Only healthy pigs will be sampled, to avoid risks inherent to manipulation of sick animals. There will be no risk for pigs as the result of the procedure. According to the estimated endemicity of human cysticercosis, we expect to find about 25% of infected pigs in this study. In the event of prevalence rates above or below the expected percentage, we will attempt to assess the causes of such discrepancies. All pig positive to 3 bands of more in the EITB will receive treatment with oxfendazole at a single dose of 30 mg/kg.

Comment: The importance of defining the prevalence of porcine cysticercosis in a village endemic for human neurocysticercosis is to confirm the existence of active transmission. If this is true, treatment of infected pigs will help to interrupt the life cycle of Taenia solium, thus reducing the prevalence of this disease in humans.

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Prevalencia de Enfermedades Neurológicas no Transmisibles en una Población Rural del Estado de Chiapas, México: Protocolo y Resultados Basales. Estudio Pro-Mas (Proyecto Comunitario La Soledad)

Objective: We aimed to assess cardiovascular health and neurological status of community-dwelling adults living in “La Soledad,” Chiapas, México, to calculate prevalence and incidence of cerebrovascular diseases, epilepsy and cognitive decline. Among others, these conditions are currently considered as the new epidemics in rural.
Design: Following a protocol similar to that used for the Atahualpa Project, we conducted a two-phase epidemiological study. During phase I, La Soledad residents were interviewed with validated field instruments to assess cardiovascular health status and well as to detect suspected stroke, epilepsy and cognitive impairment patients. During phase II, trained physicians examined suspected individuals as well as a random sample of non-suspected individuals to assess prevalence of diseases of interest.
Comment: Public health strategies must be based on the study of region-specific risk factors. Studies such the Atahualpa Project were proven to be effective for the assessment of public health problems in a rural Ecuadorian village. PROMAS will likely be cost effective to increase current knowledge on these conditions in Mexican rural villages and to promote a better cardiovascular health status among their inhabitants.

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