Mycobacterium tuberculosis induces delayed lipid droplet accumulation in dendritic cells depending on bacterial viability and virulence.

Tuberculosis remains a global health threat with high morbidity. Dendritic cells (DCs) participate in the acute and chronic inflammatory responses to Mycobacterium tuberculosis (Mtb) by directing the adaptive immune response and are present in lung granulomas. In macrophages, the interaction of lipid droplets (LDs) with mycobacteria-containing phagosomes is central to host-pathogen interactions. However, the data available for DCs are still a matter of debate. Here, we reported that bone marrow-derived DCs (BMDCs) were susceptible to Mtb infection and replication at similar rate to macrophages. Unlike macrophages, the analysis of gene expression showed that Mtb infection induced a delayed increase in lipid droplet-related genes and proinflammatory response. Hence, LD accumulation has been observed by high-content imaging in late periods. Infection of BMDCs with killed H37Rv demonstrated that LD accumulation depends on Mtb viability. Moreover, infection with the attenuated strains H37Ra and Mycobacterium bovis-BCG induced only an early transient increase in LDs, whereas virulent Mtb also induced delayed LD accumulation. In addition, infection with the BCG strain with the reintroduced virulence RD1 locus induced higher LD accumulation and bacterial replication when compared to parental BCG. Collectively, our data suggest that delayed LD accumulation in DCs is dependent on mycobacterial viability and virulence.

Socioeconomic determinants of cognition among older adults in the Brazilian longitudinal study of aging (ELSI-Brazil): a life-course approach.

BACKGROUND: The prevalence of cognitive impairment no dementia (CIND) and dementia appears to be higher in low- and middle-income countries (LMICs) compared to high-income economies. Yet few nationally representative studies from Latin American LMICs have investigated life-course socioeconomic factors associated with the susceptibility to these two cognitive conditions. Hence, the present study aimed to examine the associations of early- (education and food insecurity), mid- (employment stability), and late-life (personal income and household per capita income) socioeconomic determinants of CIND and dementia among older adults from Brazil, while simultaneously exploring whether sex plays an effect-modifier role on these associations. METHODS: This population-based study comprised a nationally representative sample of older adults (N = 5,249) aged 60 years and over from the Brazilian Longitudinal Study of Aging (ELSI-Brazil). We fitted multinomial regressions and estimated odds ratios with the respective 95% confidence intervals (CIs). RESULTS: In multivariate analyses, participants with more years of early-life education (0.89, 95% CI [0.81, 0.97]) and mid-life employment stability (0.97, 95% CI [0.96, 0.99]) and higher late-life household per capita income (0.70, 95% CI [0.51, 0.95) were less likely to have dementia. Regarding CIND, more years of mid-life employment stability (0.97, 95% CI [0.96, 0.98]) was the only determinant to confer protection. Notably, secondary sex-based analyses showed the higher the early-life educational attainment, the lower the odds of dementia in women (0.81, 95% CI [0.75, 0.87]) but not in men (1.00, 95% CI [0.86, 1.16]). CONCLUSIONS: These findings may have implications for population health and health policy by advancing our understanding of socioeconomic determinants of CIND and dementia, especially in Latin America.

Vagal dysautonomia in patients with Chagas disease and mortality: 14-year results of a population cohort of the elderly.

INTRODUCTION: Great part of Chagas disease (ChD) mortality occurs due to ventricular arrhythmias, and autonomic function (AF) may predict unfavorable outcomes. We aimed to evaluate the predictive value of AF indexes in ChD patients. METHODS: The Bambuí Study of Aging is a prospective cohort of residents ≥60 years at study onset (1997), in the southeastern Brazilian city of Bambuí (15,000 inhabitants). Consented participants underwent annual follow-up visits, and death certificates were tracked. AF was assessed by the maximum expiration on minimum inspiration (E:I) ratio during ECG acquisition and by heart rate variability indices: SDRR (standard deviation of adjacent RR intervals) and RMSSD (square root of the mean of the sum of squares of the differences between adjacent RR intervals)), calculated using a computer algorithm. Cox proportional hazards regression was performed to access the prognostic value of AF indexes, expressed as terciles, for all-cause mortality, after adjustment for demographic, clinical and ECG variables. RESULTS: From 1742 qualifying residents, 1000 had valid AF tests, being 321 with ChD. Among these, median age was 68 (64-74) years, and 32.5% were men. In Cox survival analyses, only SDRR was associated with all-cause mortality in non-adjusted models: SDRR (hazard ratio (HR): 1.26 (95% CI 1.08-1.47), p < 0.001), E:I ratio (HR: 1.13 (95% CI 0,98-1.31), p = 0.10) and RMSSD (HR: 0.99 (0.86-1.16), p = 0.95). After adjustment for sex and age, none of the indexes remained as independent predictors. CONCLUSION: Among elderly patients with ChD, AF indexes available in this cohort were not independent predictors of 14-year mortality.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Social Isolation, Loneliness, and Cognitive Performance in Older Adults: Evidence From the ELSI-Brazil Study.

BACKGROUND: The association between social isolation and cognitive performance has been less investigated in low-to-middle-income countries (LMIC) and the presence of depression as a moderator on this association has not been examined. The authors examined the associations of social isolation and perceived loneliness with cognitive performance in the Brazilian Longitudinal Study of Aging. METHODS: In this cross-sectional analysis, social isolation was evaluated by a composite score including marital status, social contact, and social support. The dependent variable was global cognitive performance, which considered memory, verbal fluency, and temporal orientation tests. Linear and logistic regressions were adjusted for sociodemographic and clinical variables. The authors added interaction terms of depressive symptoms with social isolation and loneliness to examine whether depression, measured through the Center for Epidemiologic Studies-Depression Scale, modified these associations. RESULTS: Among 6,986 participants (mean age = 62.1 ± 9.2 years), higher levels of social connections were associated with better global cognitive performance (B = 0.02, 95%CI: 0.02; 0.04). Perceived loneliness was associated with worse cognition (B = -0.26, 95%CI = -0.34; -0.18). Interactions of depressive symptoms with social connections scores were found on memory z-score and with loneliness on global and memory z-scores, suggesting a weaker association between social isolation or loneliness and cognition among those with depressive symptoms. CONCLUSION: In a large sample from an LMIC, social isolation and loneliness were associated with worse cognitive performance. Surprisingly, depressive symptoms decrease the strength of these associations. Future longitudinal studies are important to assess the direction of the association between social isolation and cognitive performance.

The association of hearing loss with depressive symptoms and cognitive function among older people: Results from the Brazilian Longitudinal Study of Aging.

OBJECTIVES: Hearing loss, depression, and cognitive decline are common among older people. We investigated the association of hearing loss with depressive symptoms and cognitive function in a nationally representative sample of people aged 50+ in Brazil. METHODS: Data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil) included information on self-reported hearing loss, hearing aid use (effective or not effective), depressive symptoms (CES-D-8), and a global cognitive score (composed of immediate and late recall, verbal fluency, orientation and prospective memory) in a sample of 9412 individuals. Multiple linear regression was used to estimate the association of hearing loss and hearing aid use with both depressive symptoms and cognitive performance. The analyses were conducted with 7837 participants with complete data, and then repeated with data from the whole sample after multiple imputation. RESULTS: Compared to those without hearing loss, those with hearing loss were more likely to have a higher number of depressive symptoms (ß: 0.53 (0.40-0.67) p < 0.001) but not worse cognitive performance (ß: -0.01 (-0.03 to 0.19) p = 0.631). Among those with hearing loss, the use of hearing aid was neither associated with cognitive performance (ß: -0.08 (-0.19 to 0.03) p = 0.169) or depressive symptoms (ß: -0.42 (-0.98 to 0.14) p = 0.143); its effective use was associated with less depressive symptoms (ß: -0.62 (-1.23 to -0.01) p = 0.045) but not worse cognitive performance (ß: -0.15 (-0.030 to 0.03) p = 0.057). Sensitivity analyses revealed that hearing loss is associated with a worse performance in two non-amnestic cognitive domains. CONCLUSIONS: Hearing loss may negatively affect specific cognitive domains and depressive symptoms among older people, and the use of a hearing aid may mitigate the association with depressive symptoms.

Subjective memory complaints: Prevalence, associated factors and sex differences in the ELSI-Brazil study.

BACKGROUND: Subjective memory complaints (SMCs) are a possible prodrome of cognitive decline but are understudied in low- and middle-income countries (LMIC). We aimed to estimate the prevalence of SMCs in a large, nationally representative sample of older adults from Brazil and to identify sociodemographic and health-related factors that are associated with SMCs independently of objective memory. METHODS: Baseline data (n = 7831) from the ELSI-Brazil study, a national representative sample of adults aged 50 and over. They were asked to rate their memory and then divided into two groups - having or not having SMCs. Logistic regression models were used to estimate the association of demographic characteristics, health related factors, objective memory performance and disability in basic (b-ADL), instrumental (i-ADL), and advanced (a-ADL) activities of daily living associated with SMCs. Whether sex was an effect modifier of the association between age and objective memory performance and SMCs was also tested. RESULTS: Of the sample, 42% (95% CI; 39.9-43.9) had SMCs, and it was higher among women (46.9%) than men (35.9%). SMC prevalence decreased with age among women and increased among men, and for both it decreased with better cognitive performance. Fully adjusted logistic regression model showed that older age, higher education, higher b-ADL scores, and better cognitive performance were associated with decreased SMCs, while being female, with higher number of chronic conditions, higher i-ADL scores, worst self-rated health, and an increased number of depressive symptoms were associated with increased SMCs. However, the interaction test (p < 0.001) confirmed that increased age was associated with decreased SMCs only among women, and that better objective memory performance was associated with decreased SMCs only among men. CONCLUSIONS: SMCs are common in the Brazilian older population and are associated with health and sociodemographic factors, with different patterns between men and women. There is a need for future studies looking at the cognitive trajectory and dementia risk in older adults with subjective cognitive complaints.

Effective primary care attenuates the association between frailty and hospital admission in old age: the ELSI-Brazil.

BACKGROUND: Frailty is a multidimensional syndrome leading to a higher hospitalization. However, few studies explicitly analyze whether measures of effective primary care modify the relationship between frailty and hospital admission. METHODS: This cross-sectional study included data from the second wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a representative community-based study with older adults aged 50 years and over, conducted in 2019-2021. Self-reported hospital admission in the past 12 months was the outcome. Frailty included the 5 phenotypic criteria: weight loss, exhaustion, low physical activity, weakness, and slowness. The effective primary care index included 12 attributes indicators, continuously. Statistical analyzes comprised logistic regression. RESULTS: Among the 7,436 study participants, frailty (odds ratio [OR] 2.17; 95% confidence intervals [95% CI] 1.31-3.62) and effective primary care index (OR 1.10; 95% CI 1.03-1.16) were positively associated with higher hospitalization. Interaction revealed that while effective primary care was positively associated with hospitalization, this association was different among frail older adults (OR 0.80; 95% CI 0.65-0.99). After stratification by frailty status, positive association with hospitalization remained only among prefrail and nonfrail individuals. The predicted probability of hospitalization tended to decrease along with higher primary care index values among frail older adults and became similar to prefrail/nonfrail at the highest end of the scale. CONCLUSIONS: Effective primary care decreases the likelihood of hospital admission among frail older adults. Interventions for delaying frailty should be initiated in primary care along with policies to strengthen primary care's organizational and provider/team-level attributes.

Frailty is a multidimensional syndrome leading to a higher hospitalization. However, few studies explicitly analyze whether measures of effective primary care modify the relationship between frailty and hospital admission. Using data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a representative community-based study with older adults aged 50 years and over, we evaluated self-reported hospital admission in the past 12 months, frailty according to 5 phenotypic criteria, and an effective primary care index with 12 attributes indicators. According to data of 7,436 study participants, we revealed that while effective primary care index was positively associated with hospital admission, this association was different among frail older adults. After stratification by frailty status, positive association with hospitalization remained only among prefrail and nonfrail individuals. Therefore, effective primary care decreases the likelihood of hospital admission among frail older adults. Interventions for delaying frailty should be initiated in primary care along with policies to strengthen primary care's organizational and provider/team-level attributes.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults. RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week). DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

Home-based gait speed and the association with sociodemographic and anthropometric variables: A national study (ELSI-Brazil).

OBJECTIVES: To investigate home-based gait speed performance for men and women stratified by age group and its associations with sociodemographic and anthropometric variables. METHODS: Data from the 2nd wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil, 2019-2021) were used. Gait speed was tested twice at home over 3.0 meters at usual pace. Associations of sociodemographic and anthropometric variables with gait speed were evaluated using gamma regression. RESULTS: Median gait speed value reduced with increasing age in both sexes [men: 0.70 m/s (50-59 years) to 0.53 m/s (≥80 years); women: 0.68 m/s (50-59 years) to 0.48 m/s (≥80 years)] and was significantly lower in women than men in the age groups of 60-69 and 70-79 years. Age group and education among men and age group, education, and waist circumference among women were significantly associated with gait speed. CONCLUSIONS: Our findings may be helpful as reference values to identify mobility limitation among older Brazilians.

Cognitive Frailty is Associated With Elevated Proinflammatory Markers and a Higher Risk of Mortality.

BACKGROUND: Cognitive impairment and physical frailty are common among older adults and associated with a higher likelihood of adverse health outcomes. These two conditions frequently coexist in the same individual as cognitive frailty, yet few studies have examined the impact of such comorbidity on clinical outcomes or underlying biological mechanisms. METHODS: A total of 1,340 older adults (age ≥60 years old) from the Bambui Cohort Study of Ageing, with a total follow-up of 10 years, were included in this study. Frailty was defined by the accumulation of deficit framework and cognitive impairment based on scores on the MMSE less than 22. In addition, serum IL-6 levels were measured by cytometric bead array assay. RESULTS: Individuals classified with cognitive frailty had significantly higher serum IL-6 levels compared to the robust, cognitively unimpaired group. Those with cognitive frailty (aOR = 1.97 [1.18-3.27] and prefrailty and cognitive impairment (aOR = 1.83 [1.24-2.69]) had the highest mortality risk over 10 years of follow-up. Higher IL-6 levels were also independently associated with a higher mortality rate (aOR = 1.37 [1.23-1.54]). CONCLUSION: Our study shows that cognitive Frailty indicates a vulnerability state and of increasing mortality risk. Our findings also suggested that proinflammatory abnormalities can be viewed as a central phenomenon underlying common age-related problems (e.g., cognitive impairment and Frailty) and outcomes (e.g., mortality).

Alcohol consumption among older adults: Findings from the ELSI-Brazil study.

OBJECTIVES: This study estimates the national prevalence of drinking patterns (current, heavy, and binge) and the associated factors, among older Brazilians. DESIGN: Cross-sectional study using survey data from ELSI-Brazil (2015-2016). SETTING/PARTICIPANTS: A total of 7839 adults aged 50 years or older. MEASUREMENTS: Respondents were asked about alcohol drinking. Alcohol consumption status was categorized as current drinkers (last month), heavy drinkers (≥7 drinks/week for females and ≥14 drinks/week for males), and binge drinkers (≥4 drinks on one occasion for females and ≥5 drinks on one occasion for males). Covariates included sociodemographic characteristics, tobacco smoking, depression, and number of chronic diseases. RESULTS: Of the 7839 participants, 29.4% were current drinkers, 5.1% were heavy drinkers, and 10.3% reported binge drinking. In the ≥60 years old age group, the prevalence of current drinking was 23.8%, 3.9% were heavy drinkers, and 6.7% reported binge drinking. All drinking patterns had similar associated factors: being male, being younger, having higher education, tobacco smoking, and falls. In addition, the greater the number of chronic conditions, the lower the prevalence of current drinking and binge drinking. CONCLUSION: Heavy drinking and binge drinking are often reported by older Brazilians, particularly among males, those with higher education and in the younger age groups. These behaviors can negatively affect the health of older adults. It is, therefore, important to identify the problems related to alcohol consumption among older adults to minimize the risks and harms.

Poor sleep quality and oral health among older Brazilian adults.

OBJECTIVES: This study evaluates the association between normative and subjective oral health measures and poor self-reported sleep quality among community-dwelling older adults in Brazil. METHODS: This was a cross-sectional study with data from the Brazilian Longitudinal Study of Aging. The dependent variable was the poor sleep quality. Independent variables of interest included number of teeth and self-reported impact of oral health on eating/chewing and on maintaining emotional stability. RESULTS: Poor sleep quality was reported by 17.8 (95% CI 16.6; 19.2) of the participants, 29% of the participants were edentulous, and 30% had 20 or more teeth. Impacts of oral health on eating and maintaining emotional stability was found among 33.3% and 20% of the older adults, respectively. After adjusting for all oral health measures and covariates, the magnitude of the associations between the number of teeth and sleep quality was attenuated. Sleep quality was related to oral health impacts on eating (OR 1.19 [95% CI 1.00; 1.41]) and on emotional stability (OR 1.51 [95% CI 1.21; 1.87]). CONCLUSIONS: This study found an association between oral health and sleep quality emphasizing the importance of oral health to general health.

Nationwide handgrip strength values and factors associated with muscle weakness in older adults: findings from the Brazilian Longitudinal Study of Aging (ELSI-Brazil).

BACKGROUND: Handgrip strength (HGS) is a simple, quick, inexpensive, and highly reliable method for the assessment of muscle strength in clinical practice and epidemiological studies. This study aimed at describing the HGS values by age group and sex in Brazilians aged 50 years and over, determining age group- and sex-specific cutoff points for muscle weakness, and investigating sociodemographic and anthropometric variables associated with muscle weakness for each sex. METHODS: Data from the second wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) were analyzed. HGS was measured in the dominant hand using a hydraulic hand dynamometer. Fractional polynomial regression models were fitted to estimate the percentiles (P5, P10, P20, P25, P50, P75, P90, and P95) of HGS by age group and sex. The P20 of the maximum HGS by age group and sex was used to define muscle weakness. Associations between sociodemographic (racial self-classification, place of residence, schooling, and monthly household income per capita in tertiles) and anthropometric variables (body mass index and waist circumference) and muscle weakness, by sex, were evaluated using logistic regression. RESULTS: The analytical sample included 7905 participants (63.1 ± 9.1 years; 60% women). HGS reduced with increasing age in both sexes. Men presented higher HGS than women in all age groups. The cutoff points for muscle weakness ranged from 28 to 15 kg for men and from 17 to 9 kg for women. In the adjusted analyses, low schooling (0-4 years) was positively associated with muscle weakness in both sexes (in men, odds ratio (OR) 2.45, 95% confidence interval (CI) 1.46-4.12; in women, OR 1.90, 95%CI 1.18-3.06). Low and middle monthly household income per capita also had a positive association with muscle weakness among women (OR 1.78, 95%CI 1.37-2.32; OR 1.32, 95%CI 1.01-1.73, respectively). Overweight had a negative association with muscle weakness among men (OR 0.66, 95%CI 0.52-0.83), and obesity was inversely associated with muscle weakness in both sexes (in men, OR 0.49, 95%CI 0.31-0.78; in women, OR 0.69, 95%CI 0.52-0.92). CONCLUSIONS: This study provides HGS values and cutoff points for muscle weakness by age group and sex from a nationally representative sample of older Brazilian adults. The variables associated with muscle weakness slightly differed between men and women. HGS values and cutoff points generated can be used as benchmarks in clinical settings and foster future epidemiological research.

Loneliness and social disconnectedness in the time of pandemic period among Brazilians: evidence from the ELSI COVID-19 initiative.

Objectives: This study aimed at estimating the pre-pandemic and pandemic prevalence of loneliness and investigating the association of loneliness with social disconnectedness during social distancing strategies in the time of the COVID-19 pandemic period.Methods: We used data from the ELSI COVID-19 initiative with participants from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), which comprised 4,431 participants aged 50 years and over. Loneliness (hardly ever/some of the time/often) was assessed by the question "In the past 30 days, how often did you feel alone/lonely?". Social disconnectedness included information on social contacts through virtual talking (i.e. telephone, Skype, WhatsApp, or social media) and outside-home meetings with people living in another household. Covariates included sociodemographic and health related characteristics. Multinomial logistic regression models were used to estimate odds ratios (OR) with their 95% confidence interval (CI).Results: The overall prevalence of loneliness during the pandemic was 23.9% (95% CI 20.7-27.5); lower than in the pre-pandemic period (32.8%; 95% CI 28.6-37.4). In the pandemic period, 20.1% (95% CI 16.9-23.6) reported some of the time feeling lonely and 3.9% (95% CI 3.1-4.8) reported often feeling lonely. In the fully adjusted model, virtual talking disconnectedness (OR=1.67; 95% CI 1.09-2.56) was positively associated with some of the time feeling lonely and outside-home disconnectedness (OR=0.33; 95% CI 0.18-0.60) was negatively associated with often feeling lonely.Conclusion: Individuals with virtual talking disconnectedness and without outside-home disconnectedness are at higher risk of loneliness during the time of COVID-19 pandemic. Stimulating virtual talking connectedness might have the potential to diminish loneliness despite steep outside-home disconnectedness.

Healthcare utilization among older Brazilians during the COVID-19 pandemic: The Brazilian Longitudinal Study of Ageing-COVID-19 initiative.

BACKGROUND: As the COVID-19 pandemic progresses, understanding its sustained impact on healthcare access and utilization represents a vital task for decision-makers and health systems. This study investigates how three aspects of health care utilization (i.e., consultations for COVID-19 related symptoms, cancelation of previously scheduled care and hospitalisation in the past 30 days) relate to individual and municipal factors in a nationally-representative sample of Brazilians aged 50 and over. METHODS: Data were obtained for 6584 participants from the second wave of the Brazilian Longitudinal Study of Ageing (ELSI-Brazil in Portuguese) who were administered supplemental telephone interviews between September and October 2020. Descriptive statistics, bivariate analysis and multivariate analysis using survey-weighted Poisson regression were applied to evaluate all three outcomes of interest (consultation, care cancelation, and hospitalisation). Predicted probabilities were also calculated to understand the overall effect of relevant covariates. RESULTS: Women were 76% less likely to seek care for COVID-19 symptoms (Odds Ratio [OR] = 0.24, 95% Confidence Interval [CI] = 0.10, 0.53) and 82% more likely to have healthcare cancelled due to the pandemic (OR = 1.82, 95% CI = 1.43, 2.33) than men. Those who live in municipalities with low coverage (<40%) of community-based primary care (the Family Health Strategy) were more likely (OR = 1.80, 95% CI = 1.00, 3.22) to be hospitalised for any reason in the past 30 days and more likely to experience healthcare cancelation (OR = 1.43, 95% CI = 1.01, 2.02). Living in the Southeast and Midwest regions was associated with 62% and 78%, respectively, lower odds of previously scheduled care being cancelled due to the pandemic, in comparison to the North region (OR = 0.38, 95% CI = 0.21, 0.67, and OR = 0.22, 95% CI = 0.14, 0.36). Living in the Southeast region was associated with over 7.61 higher odds of having sought care for COVID-19-related symptoms, relative to those living in the North (OR = 7.61, 95% CI = 2.16, 26.85). CONCLUSION: Results highlight the uneven impact of the COVID-19 pandemic on health care utilization between males and females, and across Brazilian municipalities and regions.

EPIGEN-Brazil Initiative resources: a Latin American imputation panel and the Scientific Workflow.

EPIGEN-Brazil is one of the largest Latin American initiatives at the interface of human genomics, public health, and computational biology. Here, we present two resources to address two challenges to the global dissemination of precision medicine and the development of the bioinformatics know-how to support it. To address the underrepresentation of non-European individuals in human genome diversity studies, we present the EPIGEN-5M+1KGP imputation panel-the fusion of the public 1000 Genomes Project (1KGP) Phase 3 imputation panel with haplotypes derived from the EPIGEN-5M data set (a product of the genotyping of 4.3 million SNPs in 265 admixed individuals from the EPIGEN-Brazil Initiative). When we imputed a target SNPs data set (6487 admixed individuals genotyped for 2.2 million SNPs from the EPIGEN-Brazil project) with the EPIGEN-5M+1KGP panel, we gained 140,452 more SNPs in total than when using the 1KGP Phase 3 panel alone and 788,873 additional high confidence SNPs (info score ≥ 0.8). Thus, the major effect of the inclusion of the EPIGEN-5M data set in this new imputation panel is not only to gain more SNPs but also to improve the quality of imputation. To address the lack of transparency and reproducibility of bioinformatics protocols, we present a conceptual Scientific Workflow in the form of a website that models the scientific process (by including publications, flowcharts, masterscripts, documents, and bioinformatics protocols), making it accessible and interactive. Its applicability is shown in the context of the development of our EPIGEN-5M+1KGP imputation panel. The Scientific Workflow also serves as a repository of bioinformatics resources.

Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass and fat mass indexes.

BACKGROUND/OBJECTIVES: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. SUBJECTS/METHODS: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas). RESULTS: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. CONCLUSIONS: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.