Cognitive performance and all-cause mortality in community dwellers of Amerindian ancestry living in rural Ecuador: A population-based, longitudinal prospective study.

OBJECTIVE: There is limited information on mortality risk in individuals with cognitive impairment living in rural Latin America. In this study, we assess the association between cognitive impairment and all-cause mortality in adults of Amerindian ancestry living in rural Ecuador. PATIENTS AND METHODS: Middle-aged and older adults enrolled in the population-based Three Villages Study cohort were followed prospectively in order to estimate mortality risk according to their baseline cognitive performance as determined by the Montreal Cognitive Assessment (MoCA). Results were adjusted for demographics, level of education, traditional cardiovascular risk factors, symptoms of depression, severe tooth loss, and oily fish intake (factors previously associated with mortality in the study population). RESULTS: Analysis included 1022 individuals followed for an average of 7.8 ± 3.4 years. Mean MoCA score was 21.2 ± 5.4 points (median: 22 points), with 334 (32.7%) individuals showing cognitive impairment, as evidenced by a MoCA score ≤ 19 points (the cutoff for poor cognitive performance based on previous studies in the same population). A total of 150 (14.7%) individuals died during the follow-up. Crude mortality rate was 2.87 per 100 person-years (95% C.I.: 2.08 - 3.96). For individuals with normal cognition, the mortality rate was 1.21 (95% C.I.: 0.92 - 1.50) while for those with cognitive impairment the rate increased to 3.48 (95% C.I.: 2.73 - 4.23). A multivariate Cox-proportional hazards model, confirmed that individuals with cognitive impairment had a significantly higher mortality risk than those without cognitive impairment (HR: 1.52; 95% C.I.: 1.05 - 2.18). CONCLUSIONS: Cognitive impairment is associated with mortality in the study population.

Patterns of progression of cerebral small vessel disease markers in older adults of Amerindian ancestry: a population-based, longitudinal prospective cohort study.

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.

Risk for Subsequent SARS-CoV-2 Infection and Severe COVID-19 Among Community-Dwellers With Pre-Existing Cervicocephalic Atherosclerosis: A Population-Based Study.

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.

Hypertensive Retinopathy and All-Cause Mortality in Older Adults of Amerindian Ancestry. A Population-based Longitudinal Prospective Study.

INTRODUCTION: Hypertensive retinopathy (HTRP) predicts all-cause mortality in Asian and Caucasian populations. However, little is known about HTRP impact in other ethnic groups. AIM: We sought to estimate the mortality risk according to HTRP severity in older adults of Amerindian ancestry living in rural Ecuador. METHODS: This prospective study enrolled individuals aged ≥ 60 years with baseline blood pressure ≥ 120/≥ 80 mmHg from the ongoing Atahualpa Project cohort who received retinal photographs (for HTRP grading) and a brain MRI. We ascertained all-cause mortality after a mean of 5.2 ± 1.2 years of follow-up. Cox-proportional hazards models adjusted for demographics, cardiovascular risk factors, neuroimaging signatures of cerebral small vessel disease, blood pressure determinations during follow-up and incident strokes, were obtained to estimate mortality risk according to HTRP severity. RESULTS: Analysis included 236 participants (mean age 69.3 ± 7.3 years). HTRP Grade 2 or higher was determined in 42 (18%) individuals. Fifty participants (21%) died during the follow-up, resulting in an overall unadjusted crude mortality rate of 4.1 per 100 person-years. Mortality rate in subjects with HTRP Grade 2 or higher was 7.2 and in those with no HTRP or Grade 1 only was 3.4 per 100 person-years. An adjusted Cox-proportional hazard model showed that individuals with HTRP Grade 2 or higher maintained a greater than two-fold mortality risk (HR 2.08; 95% C.I. 1.04-4.15; p = 0.038) when compared to those with no HTRP or Grade 1 only. CONCLUSION: Study results show that HTRP severity predicts mortality in this population of older adults.

Factors Associated With a Persistent Seronegative Status 1 Year After a SARS-CoV-2 Massive Infection Outbreak in Community Dwellers Living in Rural Ecuador: A Prospective Population-based Study.

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.

Hand grip strength before and after SARS-CoV-2 infection in community-dwelling older adults.

OBJECTIVE: To assess the association between SARS-CoV-2 infection and decreased hand grip strength (HGS). DESIGN: Longitudinal population-based study. SETTING: Community-dwelling older adults (aged ≥60 years) living in a rural Ecuadorian village struck by the SARS-CoV-2 pandemic. PARTICIPANTS: Of 282 enrolled individuals, 254 (90%) finished the study. MEASUREMENTS: HGS was measured 3 months before (January 2020) and 9 months after the introduction of the virus into the population (January 2021). SARS-CoV-2 antibody testing was performed in two rounds: in May-June (early) and September-November (late), 2020. An independent association between SARS-CoV-2 infection and HGS decline was assessed by fitting linear mixed models for longitudinal data. Changes in HGS scores in SARS-CoV-2 seropositive subjects, according to the time elapsed since seroconversion, were compared with those who remained seronegative. RESULTS: Overall, 149 (59%) individuals became seropositive for SARS-CoV-2. The mean HGS (in kg) was 25.3 ± 8.3 at baseline and 23.7 ± 8.1 at follow-up (p = 0.028), with 140 individuals having >5% HGS decline between both measurements. The follow-up HGS measurement decreased by 1.72 kg in seropositive individuals, and by 0.57 kg in their seronegative counterparts (p < 0.001). SARS-CoV-2 seropositive individuals were 2.27 times more likely (95% CI: 1.33-3.87) to have a lower HGS measurement at the time of follow-up than those who remained seronegative. When compared with seronegative subjects, seropositive patients with early seroconversion were 3.41 times (95% CI: 1.73-6.74) more likely to have >5% HGS decline at the time of the follow-up than those with later, i.e., more recent, infections. CONCLUSIONS: This study shows an independent deleterious impact of SARS-CoV-2 on HGS that is more marked among individuals with infections that occurred more than 8 months before follow-up HGS. Results suggest the possibility of chronic damage to skeletal muscles by SARS-CoV-2.

Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection: A longitudinal prospective study nested to a population cohort.

BACKGROUND AND PURPOSE: Neurological complications of SARS-CoV-2 infection are noticed among critically ill patients soon after disease onset. Information on delayed neurological sequelae of SARS-CoV-2 infection is nil. Following a longitudinal study design, the occurrence of cognitive decline among individuals with a history of mild symptomatic SARS-CoV-2 infection was assessed. METHODS: Stroke- and seizure-free Atahualpa residents aged ≥40 years, who had pre-pandemic cognitive assessments as well as normal brain magnetic resonance imaging and electroencephalogram recordings, underwent repeated evaluations 6 months after a SARS-CoV-2 outbreak infection in Atahualpa. Patients requiring oxygen therapy, hospitalization, and those who had initial neurological manifestations were excluded. Cognitive decline was defined as a reduction in the Montreal Cognitive Assessment (MoCA) score between the post-pandemic and pre-pandemic assessments that was ≥4 points greater than the reduction observed between two pre-pandemic MoCAs. The relationship between SARS-CoV-2 infection and cognitive decline was assessed by fitting logistic mixed models for longitudinal data as well as exposure-effect models. RESULTS: Of 93 included individuals (mean age 62.6 ± 11 years), 52 (56%) had a history of mild symptomatic SARS-CoV-2 infection. Post-pandemic MoCA decay was worse in seropositive individuals. Cognitive decline was recognized in 11/52 (21%) seropositive and 1/41 (2%) seronegative individuals. In multivariate analyses, the odds for developing cognitive decline were 18.1 times higher among SARS-CoV-2 seropositive individuals (95% confidence interval 1.75-188; p = 0.015). Exposure-effect models confirmed this association (ß = 0.24; 95% confidence interval 0.07-0.41; p = 0.006). CONCLUSIONS: This study provides evidence of cognitive decline among individuals with mild symptomatic SARS-CoV-2 infection. The pathogenesis of this complication remains unknown.

SARS-CoV-2 RNA in Swabbed Samples from Latrines and Flushing Toilets: A Case-Control Study in a Rural Latin American Setting.

Information about factors potentially favoring the spread of SARS-CoV-2 in rural settings is limited. Following a case-control study design in a rural Ecuadorian village that was severely struck by the pandemic, SARS-CoV-2 RNA were detected by real-time PCR in swabs obtained from inner and upper walls in 24/48 randomly selected latrines from case-houses and in 12/48 flushing toilets from paired control-houses (P = 0.014; McNemar's test). This association persisted in a conditional logistic regression model adjusted for relevant covariates (OR: 4.82; 95% CI: 1.38-16.8; P = 0.014). In addition, SARS-CoV-2-seropositive subjects were more often identified among those living in houses with a latrine (P = 0.002). Latrines have almost five times the odds of containing SARS-CoV-2 RNA than their paired flushing toilets. Latrines are reservoirs of SARS-CoV-2 RNA, and it cannot be ruled out that latrines could contribute to viral transmission in rural settings. Frequent disinfection of latrines should be recommended to reduce the likelihood of fecal contamination.

Sleep quality deterioration in middle-aged and older adults living in a rural Ecuadorian village severely struck by the SARS-CoV-2 pandemic. A population-based longitudinal prospective study.

STUDY OBJECTIVES: This study assessed changes in sleep quality before and after the peak of the SARS-CoV-2 pandemic in community dwellers enrolled in the Atahualpa Project. METHODS: Atahualpa residents aged ≥40 years were eligible if they had a Pittsburgh Sleep Quality Index (PSQI) 9 months before the pandemic and a lateral flow-based test for identification of SARS-CoV-2 antibodies during the peak of the pandemic. Six months later, individuals completed a follow-up PSQI. The independent relationship between SARS-CoV-2 infection and deterioration in sleep quality was assessed by fitting logistic mixed models for longitudinal data. RESULTS: Of 639 participants (mean age at baseline: 59 ± 12.8 years), 325 (51%) had SARS-CoV-2 antibodies. A total of 185 (29%) individuals at baseline and 311 (49%) at follow-up were poor sleepers (p < 0.001). Mixed logistic regression models demonstrated a significant increase in poor sleepers at follow-up (odds ratio [OR]: 2.85; 95% CI: 2.16 to 3.75), which was more marked among SARS-CoV-2 seropositive subjects (OR: 3.8; 95% CI: 2.48 to 5.81). The adjusted proportion of poor sleepers increased from 29% to 56.2% (95% CI: 50.9% to 61.6%) among SARS-CoV-2 seropositive individuals, but only to 40.7% (95% CI: 35.3% to 46.1%) in their seronegative counterparts (p < 0.001). Likewise, progression from a good to a poor sleeper status was higher among seropositive individuals than in their seronegative counterparts (38.1% vs 22.3%; p < 0.001), after adjusting for relevant covariates. CONCLUSIONS: This study shows a deleterious effect of SARS-CoV-2 in sleep quality. An effect of SARS-CoV-2 in disrupting sleep-related pathways cannot be ruled out. TRIAL REGISTRATION: The Atahualpa Project has been registered at ClinicalTrials.gov; the identifier number is NCT01627600, and the date was: 10/02/2012 (https://clinicaltrials.gov/ct2/show/NCT01627600?cond=Atahualpa&draw=2&rank=1). The Sleep Disorders substudy has been registered at ClinicalTrials.gov; the identifier number is NCT01877616, and the date was: 06/13/2013 (https://clinicaltrials.gov/ct2/show/NCT01877616?cond=Atahualpa&draw=2&rank=4).

SARS-CoV-2 in Rural Latin America. A Population-based Study in Coastal Ecuador.

Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were detected in 303/673 rural Ecuadorian adults (45%), 77% of whom had compatible clinical manifestations. Seropositivity was associated with the use of open latrines. Our findings support the fears of mass spread of SARS-CoV-2 in rural Latin America and cannot exclude a contributing role for fecal-oral transmission.

Social Determinants of Health and Risk of SARS-CoV-2 Infection in Community-Dwelling Older Adults Living in a Rural Latin American Setting.

High social risk, as measured by the social determinants of health (SDH), may increase the risk of SARS-CoV-2 infection. However, this association has not been studied in rural communities. Using the Atahualpa Project cohort, we aimed to assess the association between SDH and SARS-CoV-2 seropositivity in community-dwelling older adults living in rural Ecuador. SARS-CoV-2 antibodies were determined in 319 individuals aged ≥ 60 years that completed a validated field instrument to assess their social risk before the introduction of this novel pandemic. Multivariate models were fitted to assess the independent association between SDH-and each of their components-and SARS-CoV-2 seropositivity, after adjusting for relevant covariates. According to the Gijon scale, 102 (32%) individuals had a high social risk (≥ 10 points). A total of 141 (44%) individuals were seropositive to SARS-CoV-2. A fully-adjusted logistic regression model showed an independent) association between social risk and SARS-CoV-2 positivity (OR 1.15; 95% CI 1.04-1.27; p = 0.008). For every unit of the total SDH score, the odds of SARS-CoV-2 seropositivity increased 15% (95% CI 3.7-27%). In addition, multivariate models showed that the individual component of SDH more strongly associated with SARS-CoV-2 seropositivity was housing, which suggested that lack of basic home facilities may increase the risk of SARS-CoV-2 infection. Knowledge on the association between high social risk and SARS-CoV-2 infection is indispensable for the development of cost-effective preventive strategies for controlling modifiable factors that are in the path of SARS-CoV-2 infection among older adults living in underserved communities.

Dawson Fingers in Older Adults with Cerebral Small Vessel Disease: A Population Study.

Dawson fingers are used to differentiate multiple sclerosis (MS) from other conditions that affect the subcortical white matter. However, there are no studies evaluating the presence of Dawson fingers in subjects with cerebral small vessel disease (cSVD). We aimed to assess prevalence and -correlates of Dawson fingers in older adults with cSVD-related moderate-to-severe white matter hyperintensities (WMH). Community-dwelling older adults residing in rural Ecuador - identified by means of door-to-door surveys - underwent a brain MRI. Exams of individuals with cSVD-related moderate-to-severe WMH were reviewed with attention to the presence of Dawson fingers. Of 590 enrolled individuals, 172 (29%) had moderate-to-severe WMH. Of these, 18 (10.5%) had Dawson fingers. None had neurological manifestations suggestive of MS. Increasing age was independently associated with Dawson fingers (p = 0.017). Dawson fingers may be less specific for MS than previously thought. Concomitant damage of deep medullary veins may explain the presence of Dawson fingers in cSVD.

Late incidence of SARS-CoV-2 infection in a highly-endemic remote rural village. A prospective population-based cohort study.

Data 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% versus 77% 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.

Prevalence and Correlates of Intracranial Atherosclerotic Disease Among Community-Dwelling Older Adults of Amerindian Ancestry. The Three Villages Study.

BACKGROUND: Knowledge on the prevalence and correlates of intracranial atherosclerotic disease (ICAD) is limited. We aimed to assess prevalence, clinical and neuroimaging correlates of ICAD in a cohort of older adults of Amerindian ancestry. METHODS: The study included 581 community-dwellers aged ≥60 years (mean age 71 ± 8.4 years; 57% women) living in rural Ecuadorian villages. ICAD was identified by means of CT determinations of carotid siphon calcifications (CSC) or MRA findings of significant stenosis of intracranial arteries. Fully-adjusted logistic regression models were fitted with biomarkers of ICAD as the dependent variables. RESULTS: A total of 205 (35%) of 581 participants had ICAD, including 185 with high calcium content in the carotid siphons and 40 with significant stenosis of at least one intracranial artery (20 subjects had both biomarkers). Increasing age, high fasting blood glucose, >10 enlarged basal ganglia-perivascular spaces and non-lacunar strokes were associated with high calcium content in the carotid siphons. In contrast, male gender, moderate-to-severe white matter hyperintensities, lacunar and non-lacunar strokes were associated with significant stenosis of intracranial arteries. Stroke was more common among subjects with any biomarker of ICAD than in those with no biomarkers (29% versus 9%, p < 0.001). Significant stenosis of intracranial arteries was more often associated with stroke than high calcium content in the carotid siphons, suggesting that CSC are more likely an ICAD biomarker than causally related to stroke. CONCLUSIONS: ICAD prevalence in Amerindians is high, and is significantly associated with stroke. CSC and significant stenosis of intracranial arteries may represent different phenotypes of ICAD.

SARS-CoV-2-related mortality in a rural Latin American population.

A sudden increase in adult mortality associated with respiratory diseases was noticed in Atahualpa (a rural Ecuadorian village), coinciding with the introduction of SARS-CoV-2 in the region. From a total of 1,852 individuals aged ≥18 years, 40 deaths occurred between January and June, 2020. In addition, a seroprevalence survey showed that 45% of the adult population have SARS-CoV-2 antibodies. Verbal autopsies revealed SARS-CoV-2 as the most likely cause of death in 29 cases. The mean age of suspected or confirmed SARS-CoV-2 cases was 76.9±12.1 years, while that of those dying from unrelated causes was 60.3±20.4 years (p=0.003). The overall mortality rate was 21.6 per 1,000 population (95% C.I.: 15.9 - 29.2), almost three-quarters of it due to SARS-CoV-2 (15.7 per 1,000; 95% C.I.: 11 - 22.4). This configures a 266% of excess mortality when compared to 5.9 per 1,000 (95% C.I.: 3.3 - 10.6) deaths from other causes. When SARS-CoV-2 mortality rate was calculated in individuals aged ≥60 years, it raised up to 68.9 per 1,000 (95% C.I.: 47.8 - 98.4). After peaking in April and May, mortality significantly decreased. It is possible that the high proportion of infected individuals and the resulting herd immunity contributed to the observed reduction in mortality.

Household Clustering of SARS-CoV-2 in Community Settings: A Study from Rural Ecuador.

The SARS-CoV-2 pandemic is now expanding into the developing world with devastating consequences. Departing from a population-based study in rural Ecuador where all adult individuals (aged 40 years or older) were tested for SARS-CoV-2 IgG and IgM antibodies, we expanded it to include a house-based case-control component assessing in-house clustering and other variables potentially associated with infection. We selected houses where exactly two study participants lived and were both seropositive (case-houses), and matched 1:1 to control-houses where both were seronegative. Younger household members had an antibody test performed. Infected household members were found in 33 (92%) case-houses and in only six (17%) control-houses. In 28/29 discordant house pairs, the case-house had seropositive household members and the control-house did not (odds ratio: 28; 95% CI: 4.6-1,144). Our data demonstrate strong in-house clustering of infection in community settings, stressing the importance of early case ascertainment and isolation for SARS-CoV-2 control.

Mediation of age in the association between frailty and large artery atherosclerosis burden - A population study in community-dwelling older adults.

BACKGROUND: A systematic evaluation of the relationship between frailty and large artery atherosclerosis (LAA) burden has not been carried out. Here, we aimed to assess the association between these variables in community-dwelling older adults living in Atahualpa (rural Ecuador). METHODS: Participants underwent frailty assessment and determinations of LAA in several vascular beds. Frailty was estimated by the Edmonton Frailty Scale (EFS). LAA was investigated in the peripheral vascular bed by means of ankle-brachial index determinations, in the extracranial carotid bed by B-mode ultrasounds, and in the intracranial bed by high-resolution CT and time-of-flight MRA. Ordinal logistic regression with interaction models were fitted to assess the independent association between levels of cognitive frailty and the LAA burden. Casual mediation and sensitivity analysis, and the E value, evaluated the effect of age in this association. RESULTS: Out of 331 included individuals, 176 (53%) were robust and the remaining 47% were either pre-frail (n = 78) or frail (n = 77). Atherosclerosis affected only one (any) vascular bed in 111 (34%) individuals, two beds in 75 (23%), and three beds in 22 (7%); the remaining 123 (37%) had no evidence of atherosclerosis. Univariate analysis showed a significant inverse association between the robust status of cognitive frailty and LAA burden (p = 0.006). This association vanishes after considering the effect of covariates. Causal mediation analysis confirms that age captures 51.8% (95% C.I.: 34.6 to 97.2%) of the effect of the association. Sensitivity analysis and E-value computation find that the amount of bias provided by age is enough to explain away the effect estimate. CONCLUSIONS: This study found no independent relationship between cognitive frailty and LAA burden.