Subclinical hyperthyroidism and dementia: the Sao Paulo Ageing & Health Study (SPAH)

Background: Several epidemiologic studies have shown a possible association between thyroid function and cognitive decline. Our aim was to evaluate the association of subclinical hyperthyroidism and dementia in a population sample of older people Methods: A cross-sectional study - Sao Paulo Ageing & Health Study (SPAH) - in a population sample of low-income elderly people >= 65 years-old to evaluate presence of subclinical thyroid disease as a risk factor for dementia. Thyroid function was assessed using thyrotropic hormone and free-thyroxine as well as routine use of thyroid hormones or antithyroid medications. Cases of dementia were assessed using a harmonized one-phase dementia diagnostic procedure by the ""10/66 Dementia Research Group"" including Alzheimer's disease and vascular dementia. Logistic regression models were used to test a possible association between subclinical hyperthyroidism and dementia. Results and discussion: Prevalence of dementia and of subclinical hyperthyroidism were respectively of 4.4% and 3.0%. After age adjustment, we found an association of subclinical hyperthyroidism and any type of dementia and vascular dementia (Odds Ratio, 4.1, 95% Confidence Interval [95% CI] 1.3-13.1, and 5.3 95% CI, 1.1-26.4; respectively). Analyzing data by gender, we found an association of subclinical hyperthyroidism with dementia and Alzheimer's disease only for men (OR, 8.0; 95% CI, 1.5-43.4; OR, 12.4; 95% CI, 1.2-128.4; respectively). No women with subclinical hypothyroidism presented Alzheimer's disease in the sample. Conclusion: The results suggest a consistent association among people with subclinical hyperthyroidism and dementia.

Estimate of Dementia Prevalence in a Community Sample from Sao Paulo, Brazil

Aims: To estimate dementia prevalence and describe the etiology of dementia in a community sample from the city of Sao Paulo, Brazil. Methods: A sample of subjects older than 60 years was screened for dementia in the first phase. During the second phase, the diagnostic workup included a structured interview, physical and neurological examination, laboratory exams, a brain scan, and DSM-IV criteria diagnosis. Results: Mean age was 71.5 years (n = 1,563) and 58.3% had up to 4 years of schooling (68.7% female). Dementia was diagnosed in 107 subjects with an observed prevalence of 6.8%. The estimate of dementia prevalence was 12.9%, considering design effect, nonresponse during the community phase, and positive and negative predictive values. Alzheimer`s disease was the most frequent cause of dementia (59.8%), followed by vascular dementia (15.9%). Older age and illiteracy were significantly associated with dementia. Conclusions: The estimate of dementia prevalence was higher than previously reported in Brazil, with Alzheimer`s disease and vascular dementia being the most frequent causes of dementia. Dementia prevalence in Brazil and in other Latin American countries should be addressed by additional studies to confirm these higher dementia rates which might have a sizable impact on countries` health services. Copyright (C) 2008 S. Karger AG, Basel

Vascular diseases and old age mental disorders: an update of neuroimaging findings

Purpose of review To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer`s disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Recent findings Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. Summary As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Polymorphisms of APOE and LRP genes in Brazilian individuals with Alzheimer disease

Alzheimer disease (AD) is the most frequent cause of dementia in Western countries. Putative genetic risk factors for AD are polymorphisms in the apolipoprotein E (APOE) gene and in the low-density lipoprotein receptor-related protein (LRP) gene. Our objective was to investigate the role of the APOE coding region polymorphisms epsilon 2, epsilon 3, and epsilon 4 and APOE promoter variants A/T at position -491 and G/T at -219, as well as LRP polymorphism C/T, as risk factors for AD in Brazilian individuals. One hundred and twenty patients with probable AD, along with 120 controls were analyzed. A significant difference between patients and controls for 64 alleles was observed: frequency of this allele in AD was 0.31, and 0.10 in controls. Individuals with 2 FA alleles had a higher risk for AD than subjects with only 1 such allele; presence of 1 epsilon 2 allele proved protective. The presence of the T allele of the -219 polymorphism was also associated with an increased risk of AD, but this polymorphism is in linkage disequilibrium with APOE F polymorphisms. No significant differences between patients and controls were observed for -491 APOE or LRP polymorphisms. In this Brazilian population, both the epsilon 4 allele and T -219 polymorphism were associated with an increased risk for AD.

Diabetes, hyperglycemia and the management of cerebrovascular disease

Purpose of review Hyperglycemia is frequent in patients with cerebrovascular disease. This review article aims to summarize the recent evidence from observational studies that examined the adverse cerebrovascular effects of dysglycemic states as well as interventional studies assessing intensive management strategies for hyperglycemia. Recent findings In recent years, diabetes, prediabetic states and insulin resistance and their association with cerebrovascular disease were an important focus of research. The cerebrovascular consequences of these metabolic abnormalities were found to extend beyond ischemic stroke to covert brain infarcts, other structural brain changes and to cognitive impairment with and without dementia. Interventional studies did not reveal that more intensive management of chronic hyperglycemia and of hyperglycemia in the setting of acute stroke improves outcome. There is clear evidence, however, that the overall management of multiple risk factors and behavior modification in patients with dysglycemia may reduce the burden of cerebrovascular disease. Summary Observational studies reveal the growing burden and adverse cerebrovascular effects of dysglycemic states. Currently available interventional studies assessing more intensive strategies for the management of hyperglycemia did not prove, however, to be effective. We discuss the current evidence, pathophysiological considerations and management implications.

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR) and normotensive control rat strains (WKY and NWR). Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Cuidador familiar de seqüelados de acidente vascular cerebral: significado e implicações

O acidente vascular cerebral (AVC) está entre as principais causas de morte no mundo. Diante das incapacidades impostas pelo AVC, surge o cuidador familiar. O objetivo desta pesquisa foi analisar o significado e as implicações de se tornar cuidador de um indivíduo seqüelado de AVC. Trata-se de um estudo qualitativo, realizado com cinco cuidadores, em Londrina-PR, no período de agosto a dezembro de 2005. Os dados foram coletados por meio de entrevistas semi-estruturadas e submetidos à análise de discurso proposta por Martins e Bicudo. Da análise das entrevistas emergiram sete categorias: voltando-se para o Ser cuidado, descrevendo os cuidados, apresentando as mudanças, o apoio da espiritualidade, compreendendo o significado do cuidado, expressando as necessidades para cuidar e perspectivas para o futuro. Os resultados revelaram que ser cuidador familiar é um fenômeno complexo, que gera nos sujeitos sentimentos de alegria e felicidade concomitantes aos sentimentos de medo, ansiedade e revolta.

Valores da pressão arterial em cães pelos métodos oscilométrico e Doppler vascular

Foram comparados dois métodos não-invasivos de medida da pressão arterial, o Doppler vascular e o oscilométrico, com o objetivo de estabelecer parâmetros que possam auxiliar no diagnóstico seguro da hipertensão arterial. Para tal, foram utilizados 45 cães, machos e fêmeas, distribuídos em três grupos de acordo com o peso, pequeno, médio e grande porte. Em cada animal, procedeu-se a mensuração por meio do Doppler vascular e, em seguida, do oscilométrico. Na obtenção da pressão arterial sistólica, não houve diferença entre os métodos nos três grupos de animais, porém, na obtenção da pressão arterial diastólica, houve diferença estatística entre o Doppler vascular e o oscilométrico nos grupos de animais de pequeno e médio porte. Pôde-se concluir que valores confiáveis de pressão sistólica podem ser obtidos tanto por meio do Doppler vascular quanto do oscilométrico. Os valores da pressão arterial diastólica obtidos pelos dois métodos não se correlacionam, principalmente nos animais de pequeno e médio porte.

AT1-receptor mediated vascular damage in myocardium, kidneys and liver in rats

The systemic aspect of vascular damage induced by angiotensin II (ANG II) has been poorly explored in the literature. Considering the presence of ANG II and its specific receptor AT1, in several organs, all tissues might be potentially affected by its effects. The aims of this study were: To evaluate the early histological changes in the heart, liver and kidneys, produced by ANG II infusion, to evaluate the protective effect of losartan. Wistar rats were distributed into three groups: control (no treatment), treated with ANG II, and treated with ANG II + losartan. ANG II was continuously infused over 72 hours by subcutaneous osmotic pumps. Histological sections of the myocardium, kidneys and liver were stained and observed for the presence of necrosis. There were ANG II-induced perivascular inflammation and necrosis of the arteriolar wall in the myocardium, kidney, and liver by, which were partially prevented by losartan. There was no significant correlation between heart and kidney damage. Tissue lesion severity was lower than that of vascular lesions, without statistical difference between groups. ANG II causes vascular injury in the heart, kidneys and liver, indicating a systemic vasculotoxic effect; the mechanisms of damage/protection vary depending on the target organ; perivascular lesions may occur even when anti-hypertensive doses of losartan are used.

The relationship between cortisol concentrations in pregnancy and systemic vascular resistance in childhood

Objective. To assess the relationship between cortisol concentrations in the last trimester of pregnancy and systemic vascular resistance — SVR in childhood. Materials and methods. This study is part of a cohort involving 130 Brazilian pregnant women and their children, ages 5 to 7 years. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of 9 samples of saliva (3 in each different day), collected at the same time, early in the morning. SVR was assessed by the HDI/PulseWave CR-2000 Cardiovascular Profiling System®. Socioeconomic and demographic characteristics and life style factors were determined by a questionnaire. The nutritional status of the women and children was assessed by the body mass index — BMI. The association between maternal cortisol and SVR in childhood was calculated by multivariate linear regression analysis. Results.There were statistically significant associations between maternal cortisol and SVR (p = 0.043) and BMI-z score of the children (p = 0.027), controlling for maternal BMI, birth weight, age, and gender of the children. Conclusion. As far as we know this is the first study in the literature assessing the association between cortisol concentrations in pregnancy and SVR in childhood. Overall, the data suggest that exposure to excess glucocorticoid in the prenatal period is associated to vascular complications in childhood, predisposing to cardiovascular diseases in later life

Proteasome Inhibition Represses Unfolded Protein Response and Nox4, Sensitizing Vascular Cells to Endoplasmic Reticulum Stress-Induced Death

Background: Endoplasmic reticulum (ER) stress has pathophysiological relevance in vascular diseases and merges with proteasome function. Proteasome inhibition induces cell stress and may have therapeutic implications. However, whether proteasome inhibition potentiates ER stress-induced apoptosis and the possible mechanisms involved in this process are unclear. Methodology/Principal Findings: Here we show that proteasome inhibition with MG132, per se at non-lethal levels, sensitized vascular smooth muscle cells to caspase-3 activation and cell death during ER stress induced by tunicamycin (Tn). This effect was accompanied by suppression of both proadaptive (KDEL chaperones) and proapoptotic (CHOP/GADD153) unfolded protein response markers, although, intriguingly, the splicing of XBP1 was markedly enhanced and sustained. In parallel, proteasome inhibition completely prevented ER stress-induced increase in NADPH oxidase activity, as well as increases in Nox4 isoform and protein disulfide isomerase mRNA expression. Increased Akt phosphorylation due to proteasome inhibition partially offset the proapoptotic effect of Tn or MG132. Although proteasome inhibition enhanced oxidative stress, reactive oxygen species scavenging had no net effect on sensitization to Tn or MG132-induced cell death. Conclusion/Relevance: These data indicate unfolded protein response-independent pathways whereby proteasome inhibition sensitizes vascular smooth muscle to ER stress-mediated cell death. This may be relevant to understand the therapeutic potential of such compounds in vascular disease associated with increased neointimal hyperplasia.

Remote Cerebellar Hemorrhage (Zebra Sign) in Vascular Neurosurgery: Pathophysiological Insights

Hemorrhage in regions remote from the site of initial intracranial operations is rare, but may be fatal. Postoperative cerebellar hemorrhage as a complication of supratentorial surgery, with a radiological appearance known as zebra sign, is an increasingly recognized clinical entity and is associated mainly with vascular neurosurgery or temporal lobe resection. The pathophysiology remains unclear. Three cases of remote cerebellar hematoma occurred after neck clipping of anterior communicating artery aneurysms. All patients had similar clinical findings and underwent pterional craniotomy with the head in accentuated extension. One patient died and the two were discharged without symptoms. Cerebellar hemorrhage probably has a multifactorial origin involving positioning associated with abundant cerebrospinal fluid drainage causing cerebellar sag with resultant vein stretching and bleeding, and use of aspirin or other antiplatelet agents.

Vascular Endothelial Growth Factor Expression in Invasive Papillary Thyroid Carcinoma

Background: The vascular endothelial growth factor (VEGF) is a major promoter of endothelial growth and migration. Some studies have shown a correlation between expression of this growth factor and prognosis in several cancers, including well-differentiated thyroid cancer. Aim: We studied VEGF expression, local invasiveness, and other prognostic factors in papillary thyroid carcinoma (PTC) to test the hypothesis that the expression of VEGF is correlated with the degree of invasion of PTC. Patients and Methods: Clinical and pathological data of 76 patients with PTC were retrospectively reviewed. Group 1 consisted of patients with gross locally invasive tumors, group 2 consisted of patients with only invasion of the thyroid capsule, and group 3 consisted of patients with noninvasive PTC. Results: VEGF expression was noted within the tumor in all groups of PTC patients but was absent in the surrounding normal tissue. Older patients had higher expression of VEGF than younger patients. The age of patients with strong reaction to VEGF was 46 +/- 14 (mean +/- standard deviation), and that in patients with a weaker reaction was 39 +/- 16 (p<0.05). Only 20% of patients with a follicular variant of PTC had a strong reaction to VEGF compared with 68% of patients with classical PTC (p<0.01). Conclusions: VEGF expression appears to be an early event in the development of PTC. Whether VEGF expression promotes the progression of PTC is not known, but the answer to this question may be important in view of its greater expression in older patients, a group whose prognosis in PTC is worse.

Shear Stress Induces Nitric Oxide-Mediated Vascular Endothelial Growth Factor Production in Human Adipose Tissue Mesenchymal Stem Cells

It has been demonstrated that human adipose tissue-derived mesenchymal stem cells (hASCs) enhance vascular density in ischemic tissues, suggesting that they can differentiate into vascular cells or release angiogenic factors that may stimulate neoangiogenesis. Moreover, there is evidence that shear stress (SS) may activate proliferation and differentiation of embryonic and endothelial precursor stem cells into endothelial cells (ECs). In this work, we investigated the effect of laminar SS in promoting differentiation of hASCs into ECs. SS (10 dyn/cm(2) up to 96 h), produced by a cone plate system, failed to induce EC markers (CD31, vWF, Flk-1) on hASC assayed by RT-PCR and flow cytometry. In contrast, there was a cumulative production of nitric oxide (determined by Griess Reaction) and vascular endothelial growth factor (VEGF; by ELISA) up to 96 h of SS stimulation ( NO(2)(-) in nmol/10(4) cells: static: 0.20 +/- 0.03; SS: 1.78 +/- 0.38, n = 6; VEGF in pg/10(4) cells: static: 191.31 +/- v35.29; SS: 372.80 +/- 46.74, n = 6, P < 0.05). Interestingly, the VEGF production was abrogated by 5 mM N(G)-L-nitro-arginine methyl ester (L-NAME) treatment (VEGF in pg/10(4) cells: SS: 378.80 +/- 46.74, n = 6; SS + L-NAME: 205.84 +/- 91.66, n = 4, P < 0.05). The results indicate that even though SS failed to induce EC surface markers in hASC under the tested conditions, it stimulated NO-dependent VEGF production.