Diabetes, hemoglobin A1c, and cognitive performance in older adults: is there any impact of frailty? Evidence from the ELSI-Brazil study

Abstract The aim of this study was to evaluate the association between diabetes and cognitive performance in a nationally representative study in Brazil. We also aimed to investigate the interaction between frailty and diabetes on cognitive performance. A cross-sectional analysis of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) baseline data that included adults aged 50 years and older was conducted. Linear regression models were used to study the association between diabetes and cognitive performance. A total of 8,149 participants were included, and a subgroup analysis was performed in 1,768 with hemoglobin A1c data. Diabetes and hemoglobin A1c levels were not associated with cognitive performance. Interaction of hemoglobin A1c levels with frailty status was found on global cognitive z-score (P-value for interaction=0.038). These results suggested an association between higher hemoglobin A1c levels and lower cognitive performance only in non-frail participants. Additionally, undiagnosed diabetes with higher hemoglobin A1c levels was associated with both poor global cognitive (β=-0.36; 95%CI: -0.62; -0.10, P=0.008) and semantic verbal fluency performance (β=-0.47; 95%CI: -0.73; -0.21, P=0.001). In conclusion, higher hemoglobin A1c levels were associated with lower cognitive performance among non-frail participants. Higher hemoglobin A1c levels without a previous diagnosis of diabetes were also related to poor cognitive performance. Future longitudinal analyses of the ELSI-Brazil study will provide further information on the role of frailty in the association of diabetes and glycemic control with cognitive decline.

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus.

BACKGROUND: Pemphigus foliaceus (PF) is an epidermal autoimmune disease, characterized by the presence of autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors contribute to PF, a complex disease that is endemic in Brazil and Colombia and neighbouring countries, and in Tunisia. Long noncoding RNAs (lncRNAs) may participate in gene regulation by interacting with DNA, proteins and other RNAs. Dysregulation of lncRNAs has recently been recognized as an important coplayer in the onset or progression of complex diseases. In addition, single-nucleotide polymorphisms (SNPs) located in lncRNA genes have been associated with differential risk to cancer, autoimmunity and infection. OBJECTIVES: Here, we aimed to investigate whether SNPs in lncRNA genes are associated with differential susceptibility to endemic PF. MATERIALS AND METHODS: We integrated data from the lncRNA SNP database with genome-wide genotype data obtained for 229 patients and 6681 controls. We tested the association between endemic PF and 2080 SNPs located in lncRNAs applying logistic regression. RESULTS: The most significantly associated SNP was rs7144332 (OR = 1·63, P = 2·8 × 10-6 ), located in the lncRNA gene AL110292·1. Results for five other SNPs were suggestive of association (P < 0·001). In silico analysis indicated that five of the six SNPs impact transcription, three may influence lncRNA's secondary structure, and three may alter microRNA-lncRNA interactions. CONCLUSIONS: We showed, for the first time, that variation in lncRNA genes may influence pemphigus pathogenesis. Our findings highlight the importance of lncRNA variation in autoimmune and possibly other complex diseases and suggest polymorphisms for functional validation.

The Effects of Weight and Waist Change on the Risk of Long-Term Mortality in Older Adults- The Bambuí (Brazil) Cohort Study of Aging.

OBJECTIVE: We aimed to investigate the risk of long-term mortality associated with weight and waist circumference (WC) change among older adults, particularly the overweight and obese ones. DESIGN: Cohort Study. SETTING: The Bambuí (Brazil) Cohort Study of Aging. PARTICIPANTS: Community-dwelling elderly (n=1138). MEASUREMENTS: Weight and WC were reassessed three years after baseline. Mortality risk associated with a 5% weight/WC loss and gain was compared to that of weight/WC stability by Cox models adjusted for clinical, behavioral and social known risk factors for death (age, gender, BMI, smoking, diabetes, total cholesterol, hypertension, Chagas disease, major electrocardiographic changes, physical activity, B-type natriuretic peptide, C-reactive protein, creatinine, education and household income). RESULTS: Female sex was predominant (718; 63.1%). Mean age was 68 (6.7) years. Weight stability (696; 61.1%) was more common than weight loss (251; 22.1%) or gain (191; 16.8%). WC remained stable in 422 (37.3%), decreased in 418 (37.0%) and increased in 291 (25.7%) participants. There were 334 (29.3%) deaths over a median follow-up time of 8.0 (6.4-8.0) years from weight/WC reassessment. Weight loss (HR 1.69; 95% CI 1.30-2.21) and gain (HR 1.37; 95% CI 1.01-1.85) were associated with increased mortality, except in those who were physically active in which weight gain was associated with decreased mortality. Results were similar for participants who were overweight/obese or with abdominal obesity at baseline (HR 1.41; 95%CI 1.02-1.97 and HR 2.01; 95%CI 1.29-3.12, for weight loss and gain, respectively). WC change was not significantly associated with mortality. CONCLUSION: Although weight loss has been recommended for adults with excessive weight regardless of age, weight change might be detrimental in older adults. Rather than weight loss, clinical interventions should target healthy lifestyle behaviors that contribute to weight stability, particularly physical activity in overweight and obese older adults.

Interactive effects of ApoE polymorphism, alcohol and smoking on age-related trends of blood pressure levels in elderly men: the Bambuì Cohort Study of Ageing (1997-2008).

Data from a population-based prospective study were used to examine longitudinal changes in blood pressure (BP) and seek interactions between apolipoprotein E (ApoE) genotypes, smoking and alcohol in a cohort of 557 elderly Brazilian men. Repeated BP measurements were obtained in four waves, and multi-level random-effects pattern-mixture models were used to evaluate age-related BP trajectories while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. Alcohol was associated with high systolic BP in ε2 carriers and those with the ε3/3 genotype, but not in ε4 carriers. This was dependent on age and smoking habits: at the age of 60, expected systolic BP in alcohol drinking ε2 carriers was 16.5 mm Hg higher than in the reference group of non-smokers/non-drinkers if they were not smokers (P=0.049), and 28.6 mm Hg higher if they were also smokers (P=0.004). The youngest smoking/non-drinking ε2 carriers had lower systolic BP, but it increased rapidly and led to higher expected levels among older carriers. Alcohol consumption, alone or together with smoking, interacts with the effects of ApoE genotype on systolic BP, probably nullifying the more favourable lipid profile of ε2 carriers. The interactions of gene-modifiable risk factors have major public health implications.

Association of ApoE polymorphisms with prevalent hypertension in 1406 older adults: the Bambuí Health Aging Study (BHAS)

Apolipoprotein E (ApoE) polymorphism influences lipid metabolism, but its association with arterial hypertension is controversial. The objective of this study was to examine the association between ApoE polymorphism and prevalent hypertension in a large unselected population of older adults. Participants from the baseline of the Bambuí Health Aging Study whose ApoE genes had been genotyped were selected for this study (N = 1406, aged 60-95 years). These subjects represented 80.7 percent of the total elderly residents in Bambuí city, MG, Brazil. Hypertension was defined as a systolic blood pressure ³140 mmHg and/or a diastolic blood pressure ³90 mmHg, or the use of anti-hypertensive medication. The exposure variable was the ApoE genotype as follows: e3 carriers, e3e3; e2 carriers, e2e2 or e2e3, and e4 carriers, e3e4 or e4e4. Potential confounding variables were age, gender, traditional cardiovascular risk factors, uric acid, and creatinine levels. The prevalence of hypertension was 61.3 percent. Compared with the e3 homozygotes, neither the e2 nor the e4 carrier status was associated with hypertension (adjusted prevalence ratios = 0.94, 95 percentCI = 0.83-1.07 and 0.98, 0.89-1.07, respectively). On the other hand, the e2 allele carriers had lower LDL cholesterol levels (P < 0.001) and the e4 carriers had higher LDL cholesterol levels (P = 0.036). This study provides epidemiologic evidence that the ApoE genotype is not associated with prevalent hypertension in old age.

Apolipoprotein E polymorphism distribution in an elderly Brazilian population: the Bambuí Health and Aging Study

Apolipoprotein E (ApoE) is one of the most extensively studied genes in the context of aging, but there are few population-based studies on ApoE polymorphism in the elderly in developing countries. The objective of the present study was to assess ApoE allele and genotype distribution in a large elderly community-based sample and its association with age, sex and skin color. Participants included 1408 subjects (80.8 percent of all residents aged ³60 years) residing in Bambuí city, MG, Brazil. The DNA samples were subjected to the polymerase chain reaction amplification, followed by the restriction fragment length polymorphism technique, with digestion by HhaI. Analysis was carried out taking into consideration the six ApoE genotypes (e3/e3, e3/e4, e2/e3, e4/e4, e2/e4, and e2/e2), the three ApoE alleles, and the number of ApoE4 alleles for each individual. The e3 allele predominated (80.0 percent), followed by e4 (13.5 percent) and e2 (6.5 percent). All six possible genotypes were observed, the e3/e3 genotype being the most frequent (63.4 percent). This distribution was similar to that described in other western populations. Sex was not associated with number of ApoE4 alleles. Black skin color was significantly and independently associated with the presence of two ApoE4 alleles (age-sex adjusted OR = 7.38; 95 percentCI = 1.93-28.25), showing that the African-Brazilian elderly have a high prevalence of the e4 allele, as observed in blacks from Africa. No association between number of ApoE4 alleles and age was found, suggesting the absence of association of ApoE genotype with mortality in this population.

Detection of renal dysfunction based on serum creatinine levels in a Brazilian community: the Bambuí Health and Ageing Study

There are few population-based studies of renal dysfunction and none conducted in developing countries. In the present study the prevalence and predictors of elevated serum creatinine levels (SCr > or = 1.3 mg/dl for men and 1.1 mg/dl for women) were determined among Brazilian adults (18-59 years) and older adults (>60 years). Participants included all older adults (N = 1742) and a probabilistic sample of adults (N = 818) from Bambuí town, MG, Southeast Brazil. Predictors were investigated using multiple logistic regression. Mean SCr levels were 0.77 ± 0.15 mg/dl for adults, 1.02 ± 0.39 mg/dl for older men, and 0.81 ± 0.17 mg/dl for older women. Because there were only 4 cases (0.48 percent) with elevated SCr levels among adults, the analysis of elevated SCr levels was restricted to older adults. The overall prevalence of elevated SCr levels among the elderly was 5.09 percent (76/1494). The prevalence of hypercreatinemia increased significantly with age (chi² = 26.17, P = 0.000), being higher for older men (8.19 percent) than for older women (5.29 percent, chi² = 5.00, P = 0.02). Elevated SCr levels were associated with age 70-79 years (odds ratio [OR] = 2.25, 95 percent confidence interval [CI]: 1.15-4.42), hypertension (OR = 3.04, 95 percent CI: 1.34-6.92), use of antihypertensive drugs (OR = 2.46, 95 percent CI: 1.26-4.82), chest pain (OR = 3.37, 95 percent CI: 1.31-8.74), and claudication (OR = 3.43, 95 percent CI: 1.30-9.09) among men, and with age >80 years (OR = 4.88, 95 percent CI: 2.24-10.65), use of antihypertensive drugs (OR = 4.06, 95 percent CI: 1.67-9.86), physical inactivity (OR = 2.11, 95 percent CI: 1.11-4.02) and myocardial infarction (OR = 3.89, 95 percent CI: 1.58-9.62) among women. The prevalence of renal dysfunction observed was much lower than that reported in other population-based studies, but predictors were similar. New investigations are needed to confirm the variability in prevalence and associated factors of renal dysfunction among populations

The Bambuí health and aging study (BHAS). Prevalence of intermittent claudication in the aged population of the community of Bambuí and its associated factors.

OBJECTIVE: To assess the prevalence of intermittent claudication in the aged population of Bambuí, Brazil, and to identify the factors associated with this disease. METHODS: Population-based cross-sectional study of the aged population (>/= 60 years of age) of Bambuí. Participants were interviewed and examined, after written consent. Intermittent claudication was defined based on a standardized questionnaire. Analysis was performed using multiple logistic regression. RESULTS: Of the 1,742 elderly living in Bambuí, 1,485 (85.2%) were enrolled in the study. Thirty-seven individuals (2.5%) with intermittent claudication were identified: 28 (1.9%) males and 9 (0.6%) females. Their age brackets were: 16 (1.08%) individuals between 60 and 69 years of age, 17 (1.15%) between 70 and 79 years, and 4 (0.27%) >/= 80 years. A significant association between intermittent claudication and the following characteristics was found: male sex (OR=5.1; CI 2.4-11.0), smokers (OR=3.1; CI 1.2-8.5), ex-smokers (OR=3.4; CI 1.3-8.7), and more than 2 hospital admissions in the last 12 months (OR=2.8; CI 1.1-7.2). CONCLUSION: Disease prevalence was similar to that of other countries. The association between intermittent claudication and smoking strengthens the significance of tobacco in peripheral artery disease pathogenesis. The association of intermittent claudication and a higher number of hospital admissions suggests greater morbidity in the elderly affected.

The Bambuí Health and Aging Study (BHAS): prevalence of risk factors and use of preventive health care services.

OBJECTIVE: To describe, for the first time in Brazil, the prevalence of risk factors and the use of preventive health care services among adults 60 years and older. METHODS: This population-based study was conducted during 1996-1997 in the state of Minas Gerais, in the town of Bambuí, which is located in the municipality of the same name. In 1996 the town had 14,950 inhabitants. For the study, all the town's residents aged > or = 60 years were selected, along with a comparison sample of persons aged 18-59 years. Data were gathered using interviews and physical examinations. RESULTS: Of the 1,742 inhabitants of the town of Bambuí aged > or = 60 years, 1,606 (92.2%) participated in the interview and 1,495 (85.8%) were examined (blood pressure, anthropometric measurements, and blood tests). Among the 1,020 younger adults selected for the survey, 909 of them (89.1%) participated in the interview, and 820 of them (80.4%) underwent the physical examination. The prevalence of the following risk factors was higher among older adults than among younger adults: physical inactivity (47.7% vs. 28.0%); blood pressure 140-159 mmHg (systolic) or 90-99 mmHg (diastolic) (25.8% vs. 8.7%); blood pressure > or = 160 mmHg (systolic) or > or = 100 mmHg (diastolic) (19.1% vs. 4.1%); total cholesterol > or = 240 mg/dL (40.6% vs. 9.8%); and blood glucose > or = 126 mg/dL (12.4% vs. 2.2%). The daily consumption of fruits and vegetables was similar among the older adults and the younger ones (51.9% and 51.7%), as was also body mass index > or = 25 kg/m2 (51.6% and 56.2%). Smoking was lower among the older adults (18.7%) than among the younger ones (31.1%). The proportion of participants whose blood pressure had been checked in the preceding year was high (86.8% among the older adults and 61.2% among the younger ones), suggesting that the high prevalence of uncontrolled hypertension was not due to limited access to health care. CONCLUSIONS: For a long time it was believed that the kinds of risk factors that we found in the urban section of the municipality of Bambuí were public health problems only in large Brazilian cities. Around 72% of the municipalities in Brazil have < or = 20,000 inhabitants, and these smaller municipalities contain some 19% of the country's entire population. The high prevalence of various risk factors among the older and younger adults in Bambuí indicates a great need for health promotion and disease prevention actions. More research is needed to find out whether our results in Bambuí reflect the reality of other small towns in Brazil.

Leishmaniose tegumentar na Região Metropolitana de Belo Horizonte: aspectos clínicos, laboratoriais, terapêuticos e evolutivos (1989-1995) / Cutaneous leishmaniasis in the Metropolitan Region of Belo Horizonte: clinical, laboratorial, therapeutic and prognosis features (1989-1995)

This study investigated clinical, laboratorial, therapeutic and prognostic aspects of American cutaneous leishmaniasis in Belo Horizonte in 358 patients with cutaneous leishmaniasis (CL) and 25 with mucocutaneous leishmaniasis (MCL). Compared to CL patients, the MCL patients reported longer duration of disease and higher frequency of other diseases, suggesting that debilitation caused by leishmaniasis or other conditions might contribute to activation and/or mucous dissemination of the parasite. The sensitivity of skin test, indirect immunofluorescence reactions and direct detection of parasites was 78.4, 79.3 and 68.3%, respectively. The treatment with meglumine antimoniate presented 100% efficacy, but 59% patients had side-effects. During two years of follow-up, there were 32/318 relapses after successful treatment. Most relapses (31/32) were of CL patients treated with 15 mg Sb5+/kg/day. The negative response to skin test was the only factor associated with a significant threefold increased risk of relapse. Higher dose or longer duration of treatment might improve the prognosis in these patients.

Foram investigados aspectos clínicos, laboratoriais, terapêuticos e evolutivos da leishmaniose tegumentar americana em Belo Horizonte. O estudo incluiu 358 pacientes com leishmaniose cutânea (LC) e 25 com leishmaniose mucosa (LM). Comparados aos pacientes com LC, aqueles com LM apresentaram maior tempo de doença e relato de outras doenças concomitantes, sugerindo que a debilitação pela leishmaniose e/ou outras doenças podem contribuir para a ativação e/ou disseminação mucosa do parasito. As sensibilidades das reações intradérmica, de imunofluorescência indireta e da pesquisa direta do parasito foram de 78,4, 79,3 e 68,3%, respectivamente. O tratamento com antimoniato de meglumina foi 100% eficaz, com 59% de efeitos colaterais ao longo do tratamento. A recidiva após tratamento ocorreu em 32 (10,1%) dos 318 casos seguidos por até dois anos. A maioria das recidivas (31 dos 32 casos) ocorreu em pacientes com LC tratados com 15mg Sb5+/kg/dia. Na investigação de critérios de cura, a reação intradérmica negativa foi o único fator associado a um risco três vezes maior de recidiva. Um aumento da dose ou do tempo de tratamento talvez melhore o prognóstico nestes pacientes.

Hypertension and clustering of cardiovascular risk factors in a community in Southeast Brazil--The Bambuí Health and Ageing Study.

OBJECTIVE: A population-based prospective study was analysed to: a) determine the prevalence of hypertension; b) investigate the clustering of other cardiovascular risk factors and c) verify whether older differed from younger adults in the pattern of clustering. METHODS: The data comprised a representative sample of the population of Bambuí, Brazil. Multiple logistic regression was used to investigate the independent association between hypertension and selected factors. RESULTS: A total of 820 younger adults (82.5%) and 1494 older adults (85.9%) participated in this study. The overall prevalence of hypertension was 24.8% (SE=1.4 %), being higher in women (26.9+/-1.5%) than in men (22.0+/- 1.7%) (p=0.033). Hypertension was positively and significantly associated with physical inactivity, overweight, hypercholesterolemia hyperglycemia and hypertriglyceridemia. The coexistence of hypertension with 4 or more of these risk factors occurred 6 times more than expected by chance, after adjusting for age and sex (OR=6.3; 95%CI: 3.4-11.9). The pattern of risk factor clustering in hypertensive individuals differed with age. CONCLUSION: Our results reinforce the need to increase detection and treatment of hypertension and to approach patients' global risk profiles.