Abstract Background Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity ...might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurocognitive intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp. Methods We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT ( n =17) vs. active tDCS and CCT ( n =20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier: NCT01434836. Results Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group. Limitations Our exploratory findings should be further confirmed in prospective controlled trials. Discussion CCT and tDCS combined might be beneficial for older depressed patients, particularly for those who have cognitive resources to adequately learn and improve task performance over time. This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy.
To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline ...cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all- cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: greater than or equal to6 mo to <2.5 y). Worsening disability also impacted mortality in the period from greater than or equal to2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow- up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up. Key words: Stroke epidemiology; Cerebrovascular risk factors; Stroke prevention
The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year ...follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 44.0-57.0 years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (β=0.002, P=0.002) and hypertension (β=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (β=-0.004, P=0.042) and White ethnicity (β=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (β=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (β=-0.005, P<0.001), past smoking (β=-0.048, P=0.009), and hypertension (β=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.
Body fat distribution predicts cardiovascular events better than body-mass index (BMI). Waist circumference (WC) and neck circumference (NC) are inexpensive anthropometric measurements. We aimed to ...present the conditional distribution of WC and NC values according to BMI, stratified by age and sex, from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline data. We analyzed 15,085 ELSA-Brasil participants with complete data. We used spline quantile regression models, stratified by sex and age, to estimate the NC and WC quantiles according to BMI. To test a putative association between age and median NC or WC values, we built sex-specific median regression models using both BMI and age as explanatory variables. We present estimated 25th, 50th, 75th, and 90th percentiles for NC and WC values, according to BMI, age, and sex. Predicted interquartile intervals for NC values varied from 1.6 to 3.8 cm and, for WC values, from 5.1 to 10.3 cm. Median NC was not associated with age in men (P=0.11) nor in women (P=0.79). However, median WC increased with advancing age in both sexes (P<0.001 for both). There was significant dispersion in WC and NC values for a given BMI and age strata for both men and women. WC, but not NC values, were associated with increasing age. The smaller influence of advancing age on the relationship between BMI and NC (compared to WC) values may be useful in longitudinal studies. Key words: Nomograms; Adiposity; Body-mass index; Waist; Neck
Carotid artery assessment by ultrasound is a non-invasive evaluation of subclinical atherosclerosis and a predictor of cardiovascular events. However, ultrasound examinations are operator-dependent. ...In the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), ultrasound images have been acquired from more than 10,000 participants. In this article, we describe the reproducibility of carotid intima-media thickness (CIMT), carotid plaque detection, and carotid plaque score (defined as the number of arterial sites with plaques) using ELSA-Brasil protocol, in a subset of 118 participants. Two board-certified radiologists and a trained technician read carotid images. We calculated intra- and inter-observer intraclass correlation (ICC) for CIMT values. We also present kappa coefficients for plaque detection and weighted kappa coefficients for carotid plaque score. Participants were aged 58.2±6.6 years, and 60 (50.8%) were men. For common carotid artery CIMT measurements, intra- and inter-observer ICC values were very good to excellent, ranging from 0.90 (95% confidence interval 95%CI: 0.72-0.95) to 0.98 (95%CI: 0.97-0.99). For carotid plaque, intra- (0.96 95%CI: 0.96-0.96) and inter- (0.99 95%CI: 0.99-0.99) observer weighted kappa coefficients were very good. Intra- and inter-observer Kappa coefficients for the presence of plaques by site were good to very good, ranging from 0.69 to 1.00. In conclusion, we found very good reproducibility for carotid plaque score and CIMT measurements in the ELSA-Brasil at baseline. These results are comparable to the best findings from similar large cohorts that analyzed carotid ultrasound data.
Allantoin is the main product of uric acid oxidation and was found to be augmented in atherosclerotic plaque in human autopsy and in animal models of atherosclerosis. Uric acid is abundant in human ...plasma and is prone to oxidation in inflammatory conditions such as atherosclerosis. In this study, we found a significant increase in plasma uric acid (P=0.002) and allantoin (P=0.025) in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) that presented common carotid intima-media thickness (c-IMT) within the 75th percentile (c-IMT≥P75). Multiple linear regression showed an association of c-IMT with uric acid (β=0.0004, P=0.014) and allantoin (β=0.018, P=0.008). This association was independent of age, the traditional risk factor LDL/HDL ratio, and non-traditional risk factors: pulse pressure, neck circumference, and the inflammatory marker myeloperoxidase. The independent and strong association of allantoin with c-IMT shows that it might be a useful marker, along with other traditional risk factors, to evaluate an early stage of atherosclerosis.
Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate ...whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio OR=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.
The systematic assessment of cognitive performance of older people without cognitive complaints is controversial and unfeasible. Identifying individuals at higher risk of cognitive impairment could ...optimize resource allocation. We aimed to develop and test machine learning models to predict cognitive impairment using variables obtainable in primary care settings. In this cross-sectional study, we included 8,291 participants of the baseline assessment of the ELSA-Brasil study, who were aged between 50 and 74 years and were free of dementia. Cognitive performance was assessed with a neuropsychological battery and cognitive impairment was defined as global cognitive z-score below 2 standard deviations. Variables used as input to the prediction models included demographics, social determinants, clinical conditions, family history, lifestyle, and laboratory tests. We developed machine learning models using logistic regression, neural networks, and gradient boosted trees. Participants' mean age was 58.3±6.2 years, 55% were female. Cognitive impairment was present in 328 individuals (4%). Machine learning algorithms presented fair to good discrimination (areas under the ROC curve between 0.801 and 0.873). Extreme Gradient Boosting presented the highest discrimination, high specificity (97%), and negative predictive value (97%). Seventy-six percent of the individuals with cognitive impairment were included among the highest ranked individuals by this algorithm. In conclusion, we developed and tested a machine learning model to predict cognitive impairment based on primary care data that presented good discrimination and high specificity. These characteristics could support the detection of patients who would not benefit from cognitive assessment, facilitating the allocation of human and economic resources.
Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought ...to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (β=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings.
Thyroid diseases are common, and use of levothyroxine is increasing worldwide. We investigated the influence of gender, race and socioeconomic status on the diagnosis and treatment of thyroid ...disorders using data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of civil servants (35-74 years of age) from six Brazilian cities. Diagnosis of thyroid dysfunction was by thyrotropin (TSH), and free thyroxine (FT4) if TSH was altered, and the use of specific medications. Multivariate logistic regression models were constructed using overt hyperthyroidism/hypothyroidism and levothyroxine use as dependent variables and sociodemographic characteristics as independent variables. The frequencies of overt hyper- and hypothyroidism were 0.7 and 7.4%, respectively. Using whites as the reference ethnicity, brown, and black race were protective for overt hypothyroidism (OR=0.76, 95%CI=0.64-0.89, and OR=0.53, 95%CI=0.43-0.67, respectively, and black race was associated with overt hyperthyroidism (OR=1.82, 95%CI=1.06-3.11). Frequency of hypothyroidism treatment was higher in women, browns, highly educated participants and those with high net family incomes. After multivariate adjustment, levothyroxine use was associated with female gender (OR=6.06, 95%CI=3.19-11.49) and high net family income (OR=3.23, 95%CI=1.02-10.23). Frequency of hyperthyroidism treatment was higher in older than in younger individuals. Sociodemographic factors strongly influenced the diagnosis and treatment of thyroid disorders, including the use of levothyroxine.
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