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Background and Purpose Recent studies have suggested an association between dysfunction of the choroid plexus and the glymphatic system. However, information is inconclusive. Following a population-based study design, we aimed to assess the association between choroid plexus calcifications (CPCs)—as a surrogate of choroid plexus dysfunction—and severity and progression of putative markers of glymphatic dysfunction, including white matter hyperintensities (WMH) of presumed vascular origin and abnormally enlarged basal ganglia perivascular spaces (BG-PVS).Methods This study recruited community-dwellers aged ≥40 years living in neighboring Ecuadorian villages. Participants who had baseline head CTs and brain MRIs were included in cross-sectional analyses and those who additional had follow-up MRIs (after a mean of 6.4 ± 1.5 years) were included in longitudinal analyses. Logistic and Poisson regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess associations between CPCs and WMH and enlarged BG-PVS severity and progression.Results A total of 590 individuals were included in the cross-sectional component of the study, and 215 in the longitudinal component. At baseline, 25% of participants had moderate-to-severe WMH and 27% had abnormally enlarged BG-PVS. At follow-up, 36% and 20% of participants had WMH and enlarged BG-PVS progression, respectively. Logistic regression models showed no significant differences between CPCs volumes stratified in quartiles and severity of WMH and enlarged BG-PVS. Poisson regression models showed no association between the exposure and WMH and enlarged BG-PVS progression. Baseline age remained significant in these models.Conclusions Choroid plexus calcifications are not associated with putative markers of glymphatic system dysfunction.

To assess the association between sleep quality and all-cause mortality in community-dwelling adults living in rural Ecuador.

Background and Purpose Prospective studies on cerebral microbleeds (CMB) have departed from individuals who already have CMB at baseline. Therefore, main outcomes have usually been the composite of new lesions appearing on the follow-up among patients who already had CMB together with those who de novo developed CMB. Using the Atahualpa Project Cohort, we aimed to assess correlates of incident CMB in community-dwelling older adults free of CMB at baseline.Methods Atahualpa residents aged ≥ 60 years received baseline clinical interviews and a brain MRI. Those who were free of CMB at baseline and received follow-up brain MRI at the end of the study were included. Multivariate logistic and Poisson regression models were fitted to assess the association and the incidence rate ratio (IRR) of incident CMB according to clinical and neuroimaging variables.Results The mean age of 241 study participants was 65.6 ± 6.1 years (57% women). After 6.5 years of follow-up, 25 subjects (10.4%) developed incident CMB. A total of 37 CMB were noticed in these 25 patients. A parsimonious logistic regression model demonstrated an association between the Edmonton Frail Scale (EFS) and incident CMB (p= .043). Multivariate logistic regression models showed an association between WMH progression and incident CMB (p= .011). Using Poisson regression models, the IRR for WMH progression at follow-up was increased in subjects with incident CMB (p= .029).Conclusions Study results show a significant relationship between the EFS, WMH progression, and incident CMB. This knowledge will allow the implementation of preventive policies to reduce incident CMB and its consequences.

Background: Information on the association between disability and severity of white matter hyperintensities (WMH) among stroke-free individuals is limited. We aimed to assess this association in apparently healthy older adults. Methods: Following a population-based cross-sectional design, community-dwelling older adults received a brain MRI to grade WMH severity and the Functional Activities Questionnaire to assess the ability to perform activities of daily living. Demographics, clinical risk factors and other markers of cerebral small vessel disease were taken into consideration for analysis. Results: Unadjusted analysis showed a significant association between moderate-to-severe WMH and disability (p= 0.003) that was tempered by the effect of age. Causal mediation analysis showed that age took away 65.9% of the effect of WMH severity on disability. An interaction model showed that disability was higher only among subjects with moderate-to-severe WMH above the median age. Conclusions: Increasing age mediates the probability of WMH-related disability in stroke-free individuals.

Background and purpose Lacunes of presumed vascular origin are perceived as biomarkers of cerebral small vessel disease (cSVD), although they may also be related to other pathogenetic mechanisms. We aimed to assess whether lacunes are more often associated with intracranial artery stenosis (IAS) than with white matter hyperintensities (WMH) of presumed vascular origin (a biomarker of cSVD) in older adults.Methods This study included 585 individuals aged ≥60 years living in rural Ecuador. Logistic regression models were fitted to assess the strength of the association between IAS or moderate-to-severe WHM on one side, and lacunes on the other. Mediation analysis was used to estimate the percentage of the effect of IAS on lacunes that was mediated by WMH.Results Lacunes were noticed in 62 (11%) individuals, IAS in 39 (7%), and moderate-to-severe WMH in 169 (29%). Fourteen of 39 individuals (36%) with IAS had lacunes, which corresponded to the territory of the stenotic artery in 50% of cases. Lacunes have a larger association with IAS than with moderate-to-severe WMH. The estimated prevalence rate of lacunes independently of any confounder was 10.6% (95% C.I.: 8.3–12.9%), which increased to 22.2% in subjects with IAS, but only to 16.4% among those with moderate-to-severe WMH. Only 24.5% of the effect of IAS on lacunes was mediated by WMH.Conclusion Lacunes are more often associated with IAS than with WMH at the population level. Neuroimaging investigation of the intracranial vasculature in individuals with lacunes will provide informed-based decisions for secondary stroke prevention.

Introduction: Oily fish intake may reduce the progression of white matter hyperintensities (WMH) of presumed vascular origin due to their high content of omega-3 polyunsaturated fatty acids and other nutrients. However, information on this relationship is limited. We aimed to assess the association between oily fish intake and WMH progression in older adults living in rural coastal Ecuador.Methods: Participants of the Atahualpa Project Cohort received baseline clinical interviews and brain MRIs. Oily fish intake was calculated at every annual door-to-door survey from enrollment to the end of the study. Individuals who also received a follow-up brain MRI were included. Poisson regression models were fitted to assess the incidence rate ratio (IRR) of WMH progression according to the amount of oily fish intake, after adjusting for demographics, level of education and traditional vascular risk factors.Results: The study included 263 individuals of Amerindian ancestry aged ⩾60 years (mean age: 65.7 ± 6.2 years; 57% women). The mean oily fish intake was 8.3 ± 4 servings per week. Follow-up MRIs demonstrated WMH progression in 103 (39%) individuals after a median follow-up of 6.5 years. A multivariate Poisson regression model showed an inverse relationship between oily fish intake and WMH progression (IRR: 0.89; 95% CI: 0.84–0.95; p< 0.001). A similar model also revealed an inverse relationship between tertiles of oily fish intake and probabilities of WMH progression, which became significant when individuals allocated to the third tertile were compared to those in the first and second tertiles.Conclusion: Study results show an inverse relationship between the amount of oily fish intake and WMH progression in frequent fish consumers of Amerindian ancestry.

Background and purpose Information on the association between anatomical variants of the Circle of Willis (CoW) and intracranial atherosclerotic disease (ICAD) is limited and results are controversial. In this population-based study, we aimed to assess whether an incomplete CoW is associated with high calcium content in carotid siphons (a reliable biomarker of ICAD) in community-dwelling older adults of Amerindian ancestry.Methods Individuals aged ≥60 years enrolled in the Three Villages Study received a head computed tomography (CT) and magnetic resonance angiogram (MRA) of intracranial vessels. The CoW was classified in complete or incomplete according to the presence or absence of one A1segment of the anterior cerebral artery or one or both P1segments of posterior cerebral arteries. Calcium content in carotid siphons was rated as low or high. A multivariate logistic model was fitted to assess the independent association between incompleteness of the CoW and high calcium content in carotid siphons, after adjusting for demographics and cardiovascular risk factors.Results A total of 581 individuals were enrolled (mean age: 71 ± 8.4 years; 57% women). MRA revealed an incomplete CoW in 227 (39%) individuals, and high-resolution CT disclosed high calcium content in carotid siphons in 185 (32%). A risk factor logistic regression model showed no independent association between incompleteness of the CoW and high calcium content in carotid siphons (odds ratio: 0.91; 95% confidence interval: 0.62–1.34; p= 0.631).Conclusion Study results disclosed no association between anatomical variants of the CoW and the presence of high calcium content in carotid siphons.

Background: Conflicting reports have caused controversy on whether cysticidal drugs modify the natural course of neurocysticercosis. Purpose: To perform a meta-analysis of randomized trials assessing the effect of cysticidal drugs on neuroimaging and clinical outcomes of patients with neurocysticercosis. Data Sources: Search of MEDLINE, Cochrane Database of Systematic Reviews, and Literatura Latino-Americana y del Caribe en Ciencias de la Salud (LILACS) between 1979 and 2005. There were no language restrictions. Study Selection: Randomized trials of cysticidal drug therapy for neurocysticercosis that met predefined criteria designed to allow characterization of the disease and objective evaluation of therapy. Data Abstraction: The authors independently reviewed articles. Abstracted data included study design, number of randomly assigned patients and withdrawals, intervention, adverse events, timing of neuroimaging studies, and outcomes. Data Synthesis: Eleven studies met the inclusion criteria. Six trials randomly assigned 464 patients with cystic lesions (vesicular cysticerci), and 5 trials randomly assigned 478 patients with enhancing lesions (colloidal cysticerci). Parasites were located in the brain parenchyma or subarachnoid space at the convexity of the cerebral hemispheres. Cysticidal drug therapy was associated with complete resolution of cystic lesions (44% vs. 19%; P = 0.025). Trials on enhancing lesions showed a trend toward lesion resolution favoring the use of cysticidal drugs (72% vs. 63%; P = 0.38) that became statistically significant when an outlier trial was excluded from the analysis (69% vs. 55%; P = 0.006). Risk for seizure recurrence was lower after cysticidal treatment in patients with enhancing lesions (14% vs. 37%; P < 0.001). The single trial evaluating the frequency of seizures in patients with cystic lesions showed a 67% reduction in the rate of generalized seizures with treatment (P = 0.006). Limitations: Not all studies focused on the control of seizures as an outcome. Conclusions: Cysticidal drug therapy results in better resolution of colloidal and vesicular cysticerci, lower risk for recurrence of seizures in patients with colloidal cysticerci, and a reduction in the rate of generalized seizures in patients with vesicular cysticerci.

Background: Escalating street violence and criminal homicides have an adverse impact on psychological well-being. However, these consequences have been difficult to evaluate. Using a recently validated scale, we aimed to assess the impact of fear of crime on the psychological status of middle-aged and older adults living in a rural setting afflicted by endemic violence.Methods: Participants were selected from Atahualpa residents included in previous studies targeting psychological distress in the population. A validated scale was used to objectively quantify fear of crime in participants. Differences in symptoms of depression and anxiety between baseline and follow-up were used as distinct dependent variables and the continuous score of the fear of crime scale was used as the independent variable. Linear regression models were fitted to assess the association between the exposure and the outcomes, after adjusting for relevant confounders.Results: A total of 653 participants (mean age = 53.2 ± 11.5 years; 57% women) completed the requested tests. We found a 13% increase in symptoms of depression and anxiety during the peak of violence in the village compared with previous years. Linear regression models showed a significant association between the total score on the fear of crime questionnaire and worsening symptoms of depression (β = .24; 95% CI = 0.14-0.35) and anxiety (β = .31; 95% CI = 0.24-0.37), after adjustment for relevant confounders.Conclusions: This study shows a significant aggravating effect of fear of crime on pre-existing symptoms of depression and anxiety and a deleterious effect of these conditions on overall well-being.

Background: Progression of cerebral small vessel disease (cSVD) markers has been studied in different races/ethnic groups. However, information from individuals of Amerindian ancestry is lacking. We sought to evaluate progression patterns of cSVD markers in community-dwelling older adults of Amerindian ancestry. Methods: Following a longitudinal prospective study design, participants of the Atahualpa Project Cohort aged ≥ 60 years received a baseline brain MRI and clinical interviews. Those who also received a brain MRI at the end of the study were included. Poisson regression models were fitted to assess cSVD markers progression according to their baseline load after a median follow-up of 6.5 ± 1.4 years. Logistic regression models were fitted to assess interrelations in the progression of the different cSVD markers at the end of the study. Results: The study included 263 individuals (mean age: 65.7 ± 6.2 years). Progression of white matter hyperintensities (WMH) was noticed in 103 (39%) subjects, cerebral microbleeds in 25 (12%), lacunes in 12 (5%), and enlarged basal ganglia-perivascular spaces (BG-PVS) in 56 (21%). Bivariate Poisson regression models showed significant associations between WMH severity at baseline and progression of WMH and enlarged BG-PVS. These associations became non-significant in multivariate models adjusted for clinical covariates. Logistic regression models showed interrelated progressions of WMH, cerebral microbleeds and enlarged BG-PVS. The progression of lacunes was independent. Conclusions: Patterns of cSVD marker progression in this population of Amerindians are different than those reported in other races/ethnic groups. The independent progression of lacunes suggests different pathogenic mechanisms with other cSVD markers.

Introduction Cerebral small vessel disease (SVD) predicts all-cause mortality in Eastern Asian and Caucasian populations. However, little is known about SVD impact in individuals of different races/ethnic groups. In this study, we sought to estimate the mortality risk according to the total SVD (tSVD) score in older adults of Amerindian ancestry.Methods Participants aged ≥60 years from the prospective population-based Atahualpa Project cohort underwent brain MRI between June 2012 and June 2017. The tSVD score was calculated based on the presence of moderate-to-severe white matter hyperintensities, enlarged perivascular spaces, one or more lacune, and one or more cerebral microbleed. We ascertained all-cause mortality during post-MRI follow-up. Poisson regression and Cox-proportional hazards models adjusted for demographics and cardiovascular risk were obtained to estimate mortality risk according to the tSVD score.Results Analysis included 375 participants with available brain MRI and clinical data (mean age 69.0 ± 8.3 years, 56.3% women). The tSVD score was 0 point in 216 individuals (57.6%), 1 point in 71 (18.9%), 2 points in 53 (14.1%), and 3–4 points in 35 (9.3%). Increasing tSVD score was associated with advancing age, hypertension, low level of education, and physical inactivity. Using tSVD score of 0 as reference, a multivariate Poisson regression model showed an increased mortality for individuals with a tSVD score 3–4 points (IRR: 2.27; 95% CI: 1.20–4.28). Likewise, in the Cox-proportional model adjusted for demographics and cardiovascular risk, participants with a tSVD score 3–4 maintained a greater than two-fold mortality risk when compared to those with tSVD score of 0 points (HR: 2.32; 95% CI: 1.23–4.39).Conclusions High-burden SVD as determined by the tSVD score predicts mortality in community-dwelling older adults of Amerindian ancestry. Incidental diagnosis of covert SVD should prompt aggressive control of cardiovascular health.

Objective. Calcified neurocysticercosis has been associated with hippocampal atrophy (HA). However, the pathogenesis of this association is still elusive. This study assessed the role of epilepsy or interictal EEG abnormalities in the occurrence of HA in the Atahualpa Project cohort. Methods. Atahualpa residents aged ≥20 years, identified by means of door‐to‐door surveys, were offered an unenhanced head CT to identify neurocysticercosis cases. Individuals with cysticercotic parenchymal brain calcifications (121/1,299; 9.3%) underwent brain MRI, scalp EEG, and neurological evaluation to assess history of epilepsy. The independent association between combined exposures (epilepsy and/or EEG abnormalities) and HA (outcome) was assessed using univariate logistic regression models and a multivariate model adjusted for age, sex, level of education, alcohol intake and characteristics of calcifications. Results. A total of 112 NCC patients were enrolled (mean age: 52.2 ± 16.9 years; 67% women); the remaining nine declined consent. A single calcification was noticed in 70% of cases. Thirty‐one patients (27.7%) had HA, which was asymmetrical in 14. Calcification burden was higher among patients with HA than in their non‐atrophic counterparts (p=0.012). Eighteen patients had epilepsy, abnormal EEG recordings, or both. Nine of these 18 patients (50%) had HA as opposed to 22 of 94 patients (23%) with a normal EEG and no history of epilepsy (p=0.025). This association became borderline significant based on a multivariate logistic regression model, after adjusting for all covariates (OR: 3.26; 95% CI: 0.91‐11.68; p=0.070). In this model, having only one calcification was inversely associated with HA (OR: 0.32; 95% CI: 0.11‐0.95; p=0.039). Significance. Epilepsy and EEG abnormalities play a minor contributory role in the development of HA in neurocysticercosis patients. The burden of infection, leading to recurrent bouts of inflammation around calcified cysticerci, is a more likely contributor to HA development in patients with neurocysticercosis.

Background: Information on factors that increase mortality in remote settings is limited. This study aims to estimate the independent and joint role of several factors on mortality risk among older adults living in rural Ecuador.Methods: Participants were selected from community-dwelling older adults who were included in previous studies targeting mortality risk factors in the study population. Generalized structural equation modeling (GSEM) was utilized to evaluate prior causal assumptions, to redraw causal links, and to introduce latent variables that may help to explain how the independently significant variables are associated with mortality.Results: The study included 590 individuals (mean age: 67.9 ± 7.3 years; 57% women), followed for a median of 8.2 years. Mortality rate was 3.4 per 100 person-years. Prior work on separate multivariate Poisson and Cox models was used to build a tentative causal construct. A GSEM containing all variables showed that age, symptoms of depression, high social risk, high fasting glucose, a history of overt stroke, and neck circumference were directly associated with mortality. Two latent variables were introduced, 1 representing the impact of biological factors and another, the impact of social factors on mortality. The social variable significantly influenced the biological variable which carried most of the direct effect on mortality.Conclusions: Several factors contributed to mortality risk in the study population, the most significant being biological factors which are highly influenced by social factors. High social risk interact with biological variables and play an important role in mortality risk.

Background and Purpose Brain arterial diameters are markers of cerebrovascular disease. Demographic and anatomical factors may influence arterial diameters. We hypothesize that age, sex, height, total cranial volume (TCV), and persistent fetal posterior cerebral artery (fPCA) correlate with brain arterial diameters across populations.Methods Participants had a time-of-flight MRA from nine international cohorts. Arterial diameters of the cavernous internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery (BA) were measured using LAVA software. Regression models assessed the association between exposures and brain arterial diameters.Results We included 6,518 participants (mean age: 70 ± 9 years; 41% men). Unilateral fPCA was present in 13.2% and bilateral in 3.2%. Larger ICA, MCA, and BA diameters correlated with older age (Weighted average [WA] per 10 years: 0.18 mm, 0.11 mm, and 0.12 mm), male sex (WA: 0.24 mm, 0.13 mm, and 0.21 mm), and TCV (WA: for one TCV standard deviation: 0.24 mm, 0.29 mm, and 0.18 mm). Unilateral and bilateral fPCAs showed a positive correlation with ICA diameters (WA: 0.39 mm and 0.73 mm) and negative correlation with BA diameters (WA: −0.88 mm and −1.73 mm). Regression models including age, sex, TCV, and fPCA explained on average 15%, 13%, and 25% of the ICA, MCA, and BA diameter interindividual variation, respectively. Using height instead of TCV as a surrogate of head size decreased the R-squared by 3% on average.Conclusion Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations.

ABSTRACTData on SARS-CoV-2 transmission in rural communities is scarce or non-existent. A previous cross-sectional study in middle-aged and older adults enrolled in the Atahualpa Project Cohort demonstrated that 45% of participants had SARS-CoV-2 antibodies, 77% of whom were symptomatic. Here, we assessed the incidence of SARS-CoV-2 infection in the above-mentioned rural population. One month after baseline testing, 362 of 370 initially seronegative individuals were re-tested to assess incidence of seroconversion and associated risk factors. Twenty-eight of them (7.7%) became seropositive. The overall incidence rate ratio was 7.4 per 100 person months of potential virus exposure (95% C.I.: 4.7–10.2). Six seroconverted individuals (21.4%) developed SARS-CoV-2-related symptomatology. The only covariate significantly associated with seroconversion was the use of an open latrine. Predictive margins showed that these individuals were 2.5 times more likely to be infected (95% C.I.: 1.03–6.1) than those using a flushing toilet. Therefore, along one month, approximately 8% of seronegative individuals became infected, even after almost half of the population was already seropositive. Nevertheless, a smaller proportion of incident cases were symptomatic (21% versus77% of the earlier cases), and no deaths were recorded. Whether this decreased clinical expression resulted from a lower viral load in new infections cannot be determined. Increased seroconversion in individuals using latrines is consistent with a contributory role of fecal-oral transmission, although we cannot rule out the possibility that latrines are acting as a proxy for poverty or other unknown interacting variables.

AbstractOily fish are recommended as part of a healthy diet due to their high content of long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), proteins, and other nutrients. There is preliminary evidence of beneficial effects of ω-3 PUFAs in the prevention of sarcopenia (a major component of frailty). In this study, we aimed to assess the relationship between dietary oily fish intake and a measure of frailty – the Edmonton Frail Scale (EFS) score – in community-dwelling older adults living in rural coastal Ecuador. A total of 363 Atahualpa residents were enrolled. The mean fish servings per week were 8.8 ± 5.2 and mean EFS score was 5 ± 2.8 points. A linear regression model showed no association between the amount of oily fish intake and EFS scores. However, an interaction model, with participants stratified according to their median age and fish intake in quintiles, showed a significant effect for both variables on the EFS score (ß coefficient = 0.104; 95% C.I.: 0.003–0.206; p = 0.044). At the lowest quintile of fish intake, younger individuals have lower EFS scores than their older counterparts. As the consumption of oily fish increases, mean EFS scores margins were found to be progressively reduced in subjects aged 60–69 years but were largely unaffected in persons aged ≥70 years. It appears that oily fish intake has a positive effect on the frailty status of younger subjects but is superseded by the effects of age in the older population.

Background: Several studies have attempted to clarify the role of social determinants of health (SDH) on nutritional status of older adults, but results are inconsistent due to differences in SDH assessments at different levels of population development. In this study, we assessed this association in community-dwelling older adults living in rural Ecuador. Methods: SDH were measured by the Gijon’s Social-Familial Evaluation Scale (SFES) and nutritional status by the Mini Nutritional Assessment (MNA®). Multivariate logistic regression models were fitted to assess the association between SDH components and nutritional status. Locally weighted scatterplot smoothing (LOWESS) and a generalized linear model were used to evaluate the potential non-linearity of the association between the Gijon’s SFES and MNA®scores.Results: A total of 295 individuals (mean age: 72.1 ± 7.6 years; 58% women) were enrolled. There was an inverse association between the total Gijon’s SFES and nutritional status (OR: 0.75; 95% C.I.: 0.65-0.86; P< .001). Three of five components of the Gijon’s SFES (family situation, social relationships, and support networks) were inversely associated with nutritional status in multivariate logistic regression models. A LOWESS plot, together with a generalized linear model, showed an inverse linear relationship between the continuous Gijon’s SFES and MNA®scores. One standard deviation of increase in the continuous Gijon’s SFES score (2.39 points) decreased the MNA®score by 0.78 points.Conclusion: Study results show a significant inverse association between high social risk and a good nutritional status. Components of the Gijon’s SFES measuring social isolation are responsible for this association.

Background: COVID-19 patients may develop atherosclerosis-related complications. Whether a proportion of these patients already had asymptomatic cervicocephalic atherosclerosis before SARS-CoV-2 infection is not known. This study assessed whether pre-existing cervicocephalic atherosclerosis increased the susceptibility to SARS-CoV-2 infection or resulted in more severe or fatal COVID-19.Methods: Individuals enrolled in the Atahualpa Project cohort who received head CT (for assessing carotid siphon calcifications) and B-mode ultrasounds (for measurement of the carotid intima-media thickness) prior to the pandemic were eligible for this study. Among this cohort, those who also received serological tests for detection of SARS-CoV-2 antibodies and clinical evaluations for assessment of COVID-19 severity were enrolled. Multivariate logistic regression and exposure-effect models were fitted to assess the association between pre-existing atherosclerosis biomarkers, and SARS-CoV-2 seropositivity and COVID-19 severity.Results: Overall, 154 of 519 study participants (30%) had evidence of cervicocephalic atherosclerosis. A total of 325 (63%) individuals became SARS-CoV-2 positive, and 65 (23.5%) of seropositive individuals had severe or fatal COVID-19. The risk of SARS-CoV-2 seropositive status did not differ across individuals with and without atherosclerosis biomarkers (P= .360). Likewise, seropositive individuals with pre-existing atherosclerosis were not more prone to develop severe or fatal COVID-19 than those without evidence of atherosclerosis (P= .274). Average estimated exposure effects of pre-existing cervicocephalic atherosclerosis versus no atherosclerosis over SARS-CoV-2 seropositivity and COVID-19 severity were not significant.Conclusions: Pre-existing cervicocephalic atherosclerosis does not increase the risk of acquiring SARS-CoV-2 infection nor the severity of COVID-19 among seropositive individuals.

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Background: Both frailty and white matter hyperintensities (WMH) of presumed vascular origin are associated with enhanced expression of inflammatory biomarkers. Therefore, it is possible that pre-existing frailty predisposes to WMH progression. However, this relationship has not been explored. This population-based longitudinal prospective study aimed to assess the impact of frailty on subsequent progression of WMH in community-dwelling older adults living in rural Ecuador.Methods: Participants of the Atahualpa Project Cohort received baseline frailty assessment and brain MRIs. Frailty was evaluated by means of the Edmonton Frail Scale (EFS). WMH were graded according to the modified Fazekas scale. Individuals who received a follow-up brain MRI were included. Poisson regression models were fitted to assess the differential rate of WMH progression according to EFS score, after adjusting for demographics, level of education, and cardiovascular risk factors.Results: The study included 263 individuals aged ≥60 years (mean age: 65.7 ± 6.2 years; 57% women). The mean EFS score at baseline was 4 ± 2.3 points. Follow-up MRIs after a median follow-up of 6.5 years showed WMH progression in 103 (39%) individuals. The EFS score at baseline was associated with WMH progression in unadjusted analysis (P= .006). However, significance was not achieved in a multivariate Poisson regression model adjusted for relevant covariates (IRR: 1.07; 95% C.I.: 0.97-1.18; P= .192).Conclusions: Study results do not support an independent relationship between frailty and WMH progression, adjusting for the confounding effect of aging.

Background The SARS-CoV-2 pandemic is affecting millions of people living in rural areas of Low- and Middle-Income Countries and is causing an already anticipated devastating effect on the health and economics of these populations. More information is needed to modify behaviors that may counterbalance the consequences of mass spread of the virus in these underserved communities. This study aimed to identify factors associated with a persistent SARS-CoV-2 seronegative status 1 year after a massive infection outbreak in middle-aged and older adults living in rural Ecuador.Methods Individuals enrolled in the Atahualpa Project Cohort as of March 2020 received 5 rounds of tests for determination of SARS-CoV-2 antibodies in blood. Individuals who remained seronegative up to April 2021 were considered “persistently seronegative.” An adjusted Poisson regression model was fitted to estimate the incidence risk ratio of factors directly or inversely associated with a persistent seronegative status.Results A total of 673 individuals received baseline tests. Thirty-one declined consent or died and 429 seroconverted, leaving 213 seronegative subjects. Average SARS-CoV-2 incidence rate was 9.87 events (95% C.I.: 8.91-10.83) per 100 person-months of observation. The use of flushing toilet systems (instead of open latrines) increased 1.5 times the possibility of remaining seronegative. Likewise, every additional bedroom in the house increased by 15% the possibility of remaining seronegative. In contrast, every additional person in the house and having high cholesterol levels significantly reduced the possibility of remaining seronegative.Conclusions The use of flushing toilet systems and the number of bedrooms in the house directly influenced the possibility of remaining seronegative among individuals living in this rural setting. Study results also demonstrated a sustained transmission of the virus even after a significant proportion of the population has been infected. Our findings reinforce the mass spread of SARS-CoV-2 in rural communities.

Taenia solium and Echinococcus spp. are common parasites of humans. Most infections occur in the developing world and are closely related to poverty and ignorance. These cestodes tend to infect the CNS, where they cause complex and pleomorphic clinical syndromes, including epilepsy, chronic meningitis, acute encephalitis, focal neurological deficits and intracranial hypertension. Diagnosis of these conditions is a challenge, because clinical manifestations are nonspecific, most neuro-imaging findings are non-pathognomonic, and immunological tests have problems related to poor specificity and sensitivity. Therefore, diagnosis should always be based on objective evaluation of clinical, radiological, immunological and epidemiological data. Treatment must be individualized according to the number and location of lesions in the CNS and the viability of the parasites. The introduction of antiparasitic drugs such as praziquantel and albendazole has radically changed the prognosis in most patients with taeniosis, cysticercosis or hydatidosis.

SUMMARYTaenia solium neurocysticercosis is a common cause of epileptic seizures and other neurological morbidity in most developing countries. It is also an increasingly common diagnosis in industrialized countries because of immigration from areas where it is endemic. Its clinical manifestations are highly variable and depend on the number, stage, and size of the lesions and the host's immune response. In part due to this variability, major discrepancies exist in the treatment of neurocysticercosis. A panel of experts in taeniasis/cysticercosis discussed the evidence on treatment of neurocysticercosis for each clinical presentation, and we present the panel's consensus and areas of disagreement. Overall, four general recommendations were made: (i) individualize therapeutic decisions, including whether to use antiparasitic drugs, based on the number, location, and viability of the parasites within the nervous system; (ii) actively manage growing cysticerci either with antiparasitic drugs or surgical excision; (iii) prioritize the management of intracranial hypertension secondary to neurocysticercosis before considering any other form of therapy; and (iv) manage seizures as done for seizures due to other causes of secondary seizures (remote symptomatic seizures) because they are due to an organic focus that has been present for a long time.

Background: Information on the body composition of inhabitants of remote communities during the SARS-CoV-2 pandemic is limited. Using a longitudinal population-based study design, we assessed the association between SARS-CoV-2 infection and changes in body composition.Methods: Community-dwelling older adults living in a rural Ecuadorian village received body composition determinations before and 1 year after the pandemic as well as serological tests for detection of SARS-CoV-2 antibodies. The independent association between SARS-CoV-2 infection and abnormalities in body composition at follow-up was assessed by fitting linear mixed models for longitudinal data.Results: Of 327 enrolled individuals, 277 (85%) received baseline and follow-up body composition determinations, and 175 (63%) of them became SARS-CoV-2 seropositive. Overall, diet and physical activity deteriorated during the follow-up. Multivariate random-effects generalized least squares regression models that included the impact of time and seropositivity on follow-up body composition, showed that neither variable contributed to a worsening in body composition. Multivariate logistic regression models disclosed that the serological status at follow-up cannot be predicted by differences in body composition and other baseline covariates.Conclusions: Study results suggest no increased susceptibility to SARS-CoV-2 infection among older adults with abnormal body composition and no significant changes as a result of worse physical activity and dietary habits or seropositivity during the length of the study. Together with a previous study in the same population that showed decrease in hand-grip strength after SARS-CoV-2, results confirm that dynapenia (and not sarcopenia) is associated with SARS-CoV-2 infection in older adults.

BACKGROUND: Parasites have been implicated in the pathogenesis of human cancer. Anecdotal reports have suggested an association between neurocysticercosis and brain tumors. OBJECTIVE: To determine whether neurocysticercosis is a risk factor for cerebral glioma. DESIGN: Case-control study. SETTING: A university general hospital and a cancer referral center. PATIENTS: Forty-three consecutive patients with a cerebral glioma and 172 controls matched for age, sex, and socioeconomic status. METHODS: We determined the ratio between the frequency of neurocysticercosis in patients with a cerebral glioma and in matched controls. We also evaluated differences in the characteristics of the patients and in the histological type of the neoplasm among case patients with and without neurocysticercosis. In addition, we noted relationships between the location of the cerebral glioma and that of parasitic lesions. RESULTS: Eight (16.8%) of 43 patients with a glioma and 5 (2.9%) of 172 controls had neurocysticercosis (P&lt;.001). The odds ratio for this association was 7.63 (95% confidence interval, 2.03-31.09). Patients with glioma and neurocysticercosis were older than those without neurocysticercosis (mean [±SD] age, 62.75±18.34 years vs 44.69±14.04 years; P=.02). Glioblastoma multiforme was more frequent among case patients with neurocysticercosis than among those without neurocysticercosis (87.5% vs 48.6%); however, this difference was not statistically significant (P=.24). Six of the 8 patients with neurocysticercosis and a cerebral glioma had calcified parasitic lesions within and around the tumor. CONCLUSIONS: Results from this study suggest that neurocysticercosis is a risk factor for cerebral glioma. The intense astrocytic gliosis that surrounds calcified cysticerci, together with the suppression of the cellular immune response induced by cysticerci, may contribute to the development of malignant glial cells in patients with neurocysticercosis.

Taenia soliumcysticercosis is a major public health problem in several areas of the world. While the disease has a recognized etiologic agent, its definitive histological diagnosis is not possible in most cases because this parasite tends to lodge in cerebral tissues where routine biopsy is not feasible. Therefore, the diagnosis of human cysticercosis (and neurocysticercosis) should rest on the proper interpretation of the patients' symptoms together with data provided by radiological studies and immunologic tests for the detection of anticysticercal antibodies. Unfortunately, the pleomorphism of this parasitic disease creates confusion when non-specific clinical, radiological, or immunologic criteria alone are used to detect cases among populations or to diagnose hospitalized patients with neurological manifestations. We propose a chart of diagnostic criteria for human cysticercosis that objectively permit clinicians and health care workers to evaluate clinical, radiological, immunologic, and epidemiologic data of patients. The chart uses four degrees of criteria: absolute, major, minor, and epidemiologic, that were selected on the basis of their individual diagnostic strength. Interpretation of such criteria will result in three categories of diagnostic certainty: definitive, probable and possible, according to the likelihood that cysticercosis is present in a given person.

• The clinical and radiologic findings in 11 patients with brain-stem tuberculoma were reviewed. Clinical manifestations included various combinations of focal signs and symptoms of subacute onset, similar to those produced by other space-occupying lesions of the brain stem. Evidence of systemic tuberculosis was found in six cases (55%). Computed tomography (CT) usually showed an isodense or hyperdense brain-stem mass with abnormal contrast enhancement; associated supratentorial granulomas were found in four cases, and hydrocephalus was found in two cases. Magnetic resonance imaging showed irregular brain-stem lesions with long T1 and short T2 relaxation times. Cerebrospinal fluid findings were also nonspecific, as smears for acid-fast bacilli were most often negative. An incorrect diagnosis of pontine glioma was made in one patient. In contrast, proper integration of data from CT and magnetic resonance imaging findings, cerebrospinal fluid analysis, and x-ray films of the chest permitted an accurate diagnosis in ten cases. Prompt therapy with antituberculous drugs resulted in clinical improvement, documented by CT, in most patients. Brain-stem tuberculoma should be suspected in patients with space-occupying lesions of the brain stem who live in geographic areas where tuberculosis is endemic. Early diagnosis and prompt medical therapy are important in preventing mortality and reducing morbidity.

Background High social risk, as quantified by the social determinants of health (SDH), may lead to disability. This association has not been well explored in remote settings. Using the three Villages Study cohort, we assessed the association between SDH and disability among stroke-free older adults living in a rural Ecuadorian community.Methods SDH were measured by the use of the Gijon Scale and disability by the Functional Activities Questionnaire. All participants had a brain MRI to assess subclinical biomarkers of cerebral small vessel disease. Multivariate models were fitted to assess the association between components of SDH and disability, after adjusting for covariates of interest.Results The mean age of 478 enrolled individuals was 70.1 ± 8 years (59% women). High social risk was observed in 220 (46%) individuals and disability in 222 (46%). There was an almost direct linear relationship between SDH and disability, after taking into account the effect of age. A generalized linear model, adjusted for all included covariates, showed an independent association between social risk and disability (P< .001). In addition, multivariate models showed that independent SDH components more strongly associated with disability were worse support networks and social relationships. In contrast, the single SDH component not associated with disability was the economic status.Conclusions This study showed a robust association between SDH and disability. Economic needs were surpassed by other components of SDH. This knowledge will help to develop strategies for the control of factors that may be in the path for disability among older adults living in rural settings.

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.

Background:Arterial hypertension has been associated with severe tooth loss, but differential associations with individual components of blood pressure (BP) have scarcely been investigated. We assessed the independent associations between pulsatile/steady components of BP and severe tooth loss in community-dwelling adults residing in 3 rural Ecuadorian villages. Methods:Individuals aged ≥40 years living in Atahualpa, El Tambo, and Prosperidad were identified during door-to-door surveys. Data collection focused on the number of remaining teeth and measurements of pulsatile/steady components of BP. Multivariate models were fitted to assess independent associations between pulsatile/steady BP components and severe tooth loss, after adjusting for relevant covariates. Results:A total of 1543 individuals were included. Oral exams identified 426 (28%) individuals with severe tooth loss. BP levels ≥140/90 mm Hg were determined in 481 (31%) individuals. The mean pulse pressure (PP) level was 55.3 ± 19 mm Hg. For systolic BP (SBP), the mean level was 133.1 ± 23.5 mm Hg, and for diastolic BP (DBP) it was 77.8 ± 11.5 mm Hg. Univariate models showed significant associations between severe tooth loss and SBP and PP, but not with DBP. However, the significance was taken away in fully adjusted generalized linear models. Age remained as an independent significant covariate in models using SBP and PP. Causal mediation analyses disclosed that percentages of the effect of severe tooth loss mediated by age were 99.5% for SBP and 98.9% for PP. Conclusion:This study shows that age captures most of the effect of the association between pulsatile components of BP and severe tooth loss.

The first studies on specific drug therapy for neurocysticercosis (NCC) appeared more than one decade ago.1-5 As usually occurs with pioneer work with many other drugs, such studies only included anecdotal case reports or small series of patients with different forms of the disease. Therefore, the efficacy of anticysticercal drugs was difficult to evaluate. A new age of knowledge on medical treatment for NCC began when Sotelo and coworkers6,7 published the first controlled trials of praziquantel therapy in patients with parenchymal brain cysts. The authors used historical controls to demonstrate that viable cysticerci may live unchanged for several years within the brain parenchyma and that a course with praziquantel at daily doses of 50 mg per kilogram of body weight for 15 days destroys more than 60% of these cysts in less than 3 months. Using a similar design, several articles from different areas of the world further

• To determine sex-related differences in the severity of host inflammatory reaction to cysticercosis, we studied computed tomographic findings in 100 patients with parenchymal neurocysticercosis and cerebrospinal fluid results in 239 patients with subarachnoid neurocysticercosis. Computed tomographic and cerebrospinal fluid data in male subjects were compared with those obtained in female subjects. We found that when cysticerci are found in brain parenchyma, women develop a greater degree of inflammation; such differences disappear when cysticerci are found in the subarachnoid space. Our results point out the possibility of a factor located within brain parenchyma that accounts for the observed sex-related differences in the severity of immune response to the parasite; this factor could also play a role in the pathogenesis of other immunologically mediated diseases of the brain that may occur more frequently in women. To our knowledge, this study is the first in demonstrating that sex is a risk factor for the severity of inflammatory response within brain parenchyma to a parasitic disease.(Arch Intern Med 1988;148:544-546)

• Seven patients with neurocysticercosis presented with a lacunar syndrome. Four patients had sensorimotor stroke, two had pure motor hemiparesis, and one had ataxic hemiparesis. In every patient, computed tomography or magnetic resonance imaging or both showed a lacunar infarct that was secondary to the occlusion of a terminal vessel affected by endarteritis and was most commonly associated with cysticerci in the suprasellar cistern. Diagnosis of neurocysticercosis was difficult on clinical grounds, but proper integration of data from computed tomography and cerebrospinal fluid analysis provided an accurate diagnosis in every case. Neurocysticercosis should be considered in the differential diagnosis of young adults with a lacunar syndrome who come from areas of the world where this disease is endemic.

IN REPLY We would like to answer that the undue concerns of Garg and Agrawal are typical of those who are not familiar with the medical treatment of neurocysticercosis. As several different aspects were commented on in their letter, I would like to analyze them step by step.1. They stated that patients with epilepsy due to single viable cysticerci (hypodense cystic lesions) have not been reported. I would like to bring to their attention our article1 on epilepsy due to neurocysticercosis published more than 3 years ago. In that study, 30 (15%) of 203 patients had epilepsy caused by a single hypodense cystic lesion. In addition, several reports on drug therapy for parenchymal neurocysticercosis had included patients with single hypodense cystic lesions who presented with epilepsy as the primary or sole manifestation of the disease.2-52. Garg and Agrawal stated that "several" deaths have occurred as the result

TO THE EDITOR. —I have read with interest the article by Alarcón et al,1 as it showed that the length of albendazole therapy for parenchymal brain cysticercosis could be considerably shortened without lessening its efficacy. The authors did not state, however, how the 3-day course of albendazole treatment was chosen. Was it chosen on an empirical basis? If so, a larger number of patients was needed to support their findings.Albendazole is an imidazole with intense antiparasitic properties that has largely replaced praziquantel as the drug of choice for parenchymal brain cysticercosis.2-4 The initial length of 30 days of albendazole therapy for neurocysticercosis5 was settled according to that previously used for the treatment of human hydatidosis.6 When treating patients with cysticercosis, however, two observations suggested that the therapeutic effect of the drug occurred far before the full course of 30 days was completed: first, most patients

Cysticercosis is the commonest parasitic disease of the central nervous system and is endemic not only in developing countries but in industrialized nations with high rates of immigration from endemic areas. Clinical manifestations of neurocysticercosis are nonspecific and depend mainly on the number and the topography of the lesions, the host immune response to the parasite, and the sequelae of previous infections. Diagnosis is difficult on clinical grounds, but integration of data from computed tomography and cerebrospinal fluid analysis permits accurate diagnosis of most cases. Therapy for neurocysticercosis is also varied and must be individualized according to the activity of the disease and location of cysticerci. In this paper, the experience of the authors with neurocysticercosis is summarized and current information on several controversial aspects of this disease is reviewed.

TO THE EDITOR. —Ataxic hemiparesis is a heterogeneous syndrome caused by different types of lesions at both supratentorial and infratentorial levels.1-5 Etiologic considerations for this syndrome include infarction,1-3 hemorrhage,4 and neoplasms.5 Parasitic diseases of the central nervous system can conceivably produce this syndrome, but, to our knowledge, no such case has been reported. Herein, we describe a patient with neurocysticercosis (NCC) and ataxic hemiparesis.Computed tomographic scans showing (left) hypodense suprasellar mass with extension into right sylvian fissure, consistent with subarachnoidal cysticercosis, and (right) ill-defined area of low density just above right cerebral peduncle. REPORT OF A CASE. —A 38-year-old previously healthy man suddenly experienced weakness of the left leg and clumsiness of the left hand. On admission, his blood pressure was 130/80 mm Hg; his general physical examination was normal. Neurologic examination showed left hemiparesis with crural predominance, left Babinski's sign, and poor performance on