Qualidade de vida de idosos brasileiros e portugueses: uma análise comparativa / Análisis comparativo de la calidad de vida de los adultos mayores de Brasil y Portugal / Quality of Life in Older Adults in Brazil and Portugal: A Comparative Analysis

Introdução: A longevidade tornou-se uma das maiores conquistas da segunda metade do século XX. Objetivo: Comparar a qualidade de vida de idosos brasileiros e portugueses usuários da atenção primária à saúde. Materiais e Métodos: Estudo quantitativo, transversal e comparativo, aplicado a amostra probabilística englobando 294 idosos acompanhados pela Saúde da Família divididos em dois grupos: 130 idosos em Benevides/Brasil, e 164 em Coimbra/Portugal, no período de 2015-2017. A caracterização sociodemográfica e avaliação da qualidade de vida foram obtidos pelo instrumento World Health Organization Questionnaire of Quality of Life (WHOQOL-bref), consta de 26 questões divididas em quatro domínios: físico, psicológico, relações sociais e meio ambiente. Aplicado o Teste U de Mann-Whitney para análise estatística comparativa. Resultados: Nos grupos verificou-se predomínio do sexo feminino, casados, aposentados e com baixo grau de escolaridade (1 a 4 anos). A média da distribuição etária foi 70 anos para brasileiros e 76 anos para portugueses; na comparação da qualidade de vida, os idosos brasileiros obtiveram os melhores escores no domínio psicológico (79,1) enquanto portugueses tiveram melhor escore no domínio meio ambiente (65,6). Em Benevides o escore mais baixo foi o domínio meio ambiente (56,3) e, em Coimbra, o domínio com escore mais baixo foi o físico (60,7). Discussão: A qualidade de vida no envelhecimento é importante preditor para a preservação da autonomia do idoso. Conclusões: Estes resultados ampliam a concepção da importância da atenção integral no processo de envelhecimento com vista a proporcionar melhor qualidade de vida contribuindo para satisfazer as necessidades especificas da população idosa.

Introduction: Longevity is one of the greatest achievements in the last half of the 20th century. Objective: To compare the quality of life in older adults in Brazil and Portugal receiving primary health care. Materials and Methods: A comparative cross-sectional quantitative study was conducted with a probability sample of 294 older adults, who had been assisted with the Family Health strategy, being divided into two groups: 130 older adults living in Benevides, Brazil and 164 in Coimbra, Portugal during 2015 and 2017. The sociodemographic characterization and the quality of life assessment were determined through the WHO Quality of Life-BREF (WHOQOL-BREF), which consists of 26 questions assessing four domains: physical health, psychological health, social relationships and environment. The Mann-Whitney U test was applied for comparative statistical analysis. Results: There was a prevalence of married, retired women with a lower level of education (1 to 4 years) in the groups. The average age was 70 years in Brazil and 76 years in Portugal. In terms of quality of life, Brazilian older adults got better scores in the psychological health domain (79.1%) while Portuguese older adults scored best in the environmental domain (65.6%). The lowest scores were found in the environmental domain in Benevides (56.3%) and in the physical health domain in Coimbra (60.7%). Discussion: Quality of life in aging is a major predictor for the preservation of autonomy in older adults. Conclusion: These results help to broaden the importance of comprehensive care in the aging process to provide a better quality of life, which contributes to meeting the specific needs of older population.

Introducción: La longevidad se ha convertido en uno los mayores logros de la segunda mitad del siglo XX. Objetivo: Comparar la calidad de vida de los adultos mayores de Brasil y Portugal que reciben atención primaria de salud. Materiales y métodos: Se realizó un estudio cuantitativo transversal comparativo con una muestra probabilística de 294 adultos mayores que fueron acompañados por la estrategia de Salud Familiar y divididos en dos grupos: 130 adultos mayores ubicados en Benevides, Brasil y 164 en Coímbra, Portugal durante 2015 y 2017. La caracterización sociodemográfica y la evaluación de la calidad de vida se obtuvieron mediante el Cuestionario de Calidad de Vida de la Organización Mundial de la Salud (WHOQOL-BREF), que consta de 26 preguntas divididas en cuatro áreas: salud física, salud psicológica, relaciones sociales y ambiente. Se aplicó la prueba U de Mann-Whitney para el análisis estadístico comparativo. Resultados: En los grupos se observó el predominio de las mujeres casadas, jubiladas y con baja escolaridad (entre 1 y 4 años). La edad media fue de 70 años en Brasil y 76 años en Portugal. En cuanto a la calidad de vida, los adultos mayores brasileños obtuvieron mejores puntuaciones en el área de salud psicológica (79.1%) mientras que los adultos mayores portugueses tuvieron la mejor puntuación en el área ambiental (65.6%). Las puntuaciones más bajas se presentaron en el área ambiental en Benevides (56.3%) y en la salud física (60.7%) en Coímbra. Discusión: La calidad de vida en el proceso de envejecimiento es un importante predictor para la preservación de la autonomía de los adultos mayores. Conclusiones: Estos resultados amplían la concepción de la importancia de la atención integral en el proceso de envejecimiento para brindar una mejor calidad de vida, lo que contribuye a satisfacer las necesidades específicas de la población de edad avanzada.

APOEɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer's Disease.

BACKGROUND: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer's disease (AD) conversion remain controversial. OBJECTIVE: Evaluate whether TOMM40 poly-T (TOMM40' 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype. METHODS: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism. MCI patients were subdivided into two groups, the group of patients that converted to AD (MCI-AD) and the group of those that remained stable (MCI-S). RESULTS: TOMM40' 523 L allele was significantly more frequent in the MCI-AD group and having at least one L allele significantly increased the risk of conversion from MCI to AD (OR = 8.346, p < 0.001, 95% CI: 2.830 to 24.617). However, when adjusted for the presence of APOEɛ4 allele, both the L allele and ɛ4 allele lost significance in the model (p > 0.05). We then analyzed the APOEɛ4-TOMM40' 523 L haplotype and observed that patients carrying this haplotype had significantly higher risk (OR = 5.83; 95% CI = 2.30-14.83) and mean lower times of conversion to AD (p = 0.003). This haplotype was also significantly associated with a biomarker profile compatible with AD (p = 0.007). CONCLUSION: This study shows that the APOEɛ4-TOMM40' 523 L haplotype is associated with a higher risk and shorter times of conversion from MCI to AD, possibly driven by CSF biomarkers and mitochondrial dysfunction.

Underlying Biological Processes in Mild Cognitive Impairment: Amyloidosis Versus Neurodegeneration.

The amyloid cascade hypothesis proposes amyloid-ß (Aß) as the earliest and key pathological hallmark of Alzheimer's disease (AD), but this mandatory "amyloid-first pathway" has been contested. Longitudinal studies of mild cognitive impairment (MCI) patients represent an opportunity to investigate the intensity of underlying biological processes (amyloidosis versus neurodegeneration) and their relevance for progression to AD. We re-examined our cohort of amnestic MCI, grouped according to cerebrospinal fluid (CSF) biomarkers, aiming at establishing their prognostic value for Alzheimer-type dementia and testing the hypothetical model of biomarkers sequence, based on the amyloid cascade. Our baseline population consisted of 217 MCI patients, 63% with neurodegeneration markers and 47% with amyloidosis. Within the longitudinal study-group (n = 165), 85 progressed to AD and 80 remained cognitively stable. Age, CSF Aß42, and t-Tau were identified as the best single predictors of conversion to AD. Regarding MCI classification according to the NIA-AA criteria, the high-AD-likelihood group (HL-both amyloid and neurodegeneration markers) was the most frequent (42%); followed by the Suspected Non-Alzheimer Pathophysiology group (SNAP-26%), the low-AD-likelihood group (LL-negative biomarkers-22%), and the Isolated Amyloid Pathology group (IAP-10%). Risk of progression to AD was higher in HL in relation to the LL group (HR = 6.1, 95% CI = 2.1-18.0, p = 0.001). SNAP and IAP groups were equivalent in terms of risk of progression to AD (IAP: HR = 2.6, 95% CI = 0.7-9.3, p = 0.141; SNAP: HR = 3.1, 95% CI = 1.1-9.6; p = 0.046), but only SNAP was significantly different from the LL group. These results support different neurobiological pathways to AD beyond the amyloid hypothesis, highlighting the alternative "neurodegeneration-first pathway" for further investigation.

Addition of the Aß42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aß42 concentration to the level of total amyloid beta (Aß), using the Aß42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aß42/40 ratio would improve MCI categorization and more accurately predict progression to AD. METHODS: Our baseline population consisted of 197 MCI patients, of which 144 had a follow-up ≥ 2 years, and comprised the longitudinal study group. To establish our own CSF Aß42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging-Alzheimer Association criteria for MCI. RESULTS: When using the core CSF biomarkers (Aß42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing Aß42 by the Aß42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42-59%) and in the proportion of interpretable biological profiles (61-75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the Aß42/40 ratio, instead of Aß42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization. CONCLUSIONS: Our results confirm the usefulness of the CSF Aß42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.

Brain GLP-1/IGF-1 Signaling and Autophagy Mediate Exendin-4 Protection Against Apoptosis in Type 2 Diabetic Rats.

Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein. Accordingly, the insulinotropic anti-T2D drugs from glucagon-like peptide-1 (GLP-1) mimetics, namely, exendin-4 (Ex-4), could be a promising therapy. In line with this, we hypothesized that peripherally administered Ex-4 rescues brain intracellular signaling pathways, promoting autophagy and ultimately protecting against chronic T2D-induced apoptosis. Thus, we aimed to explore the effects of chronic, continuous, subcutaneous (s.c.) exposure to Ex-4 in brain cortical GLP-1/insulin/insulin-like growth factor-1 (IGF-1) signaling, and in autophagic and cell death mechanisms in middle-aged (8 months old), male T2D Goto-Kakizaki (GK) rats. We used brain cortical homogenates obtained from middle-aged (8 months old) male Wistar (control) and T2D GK rats. Ex-4 was continuously administered for 28 days, via s.c. implanted micro-osmotic pumps (5 µg/kg/day; infusion rate 2.5 µL/h). Peripheral characterization of the animal models was given by the standard biochemical analyses of blood or plasma, the intraperitoneal glucose tolerance test, and the heart rate. GLP-1, insulin, and IGF-1, their downstream signaling and autophagic markers were evaluated by specific ELISA kits and Western blotting. Caspase-like activities and other apoptotic markers were given by colorimetric methods and Western blotting. Chronic Ex-4 treatment attenuated peripheral features of T2D in GK rats, including hyperglycemia and insulin resistance. Furthermore, s.c. Ex-4 enhanced their brain cortical GLP-1 and IGF-1 levels, and subsequent signaling pathways. Specifically, Ex-4 stimulated protein kinase A (PKA) and phosphoinositide 3-kinase (PI3K)/Akt signaling, increasing cGMP and AMPK levels, and decreasing GSK3ß and JNK activation in T2D rat brains. Moreover, Ex-4 regulated several markers for autophagy in GK rat brains (as mTOR, PI3K class III, LC3 II, Atg7, p62, LAMP-1, and Parkin), ultimately protecting against apoptosis (by decreasing several caspase-like activities and mitochondrial cytochrome c, and increasing Bcl2 levels upon T2D). Altogether, this study demonstrates that peripheral Ex-4 administration may constitute a promising therapy against the chronic complications of T2D affecting the brain.

[Relevant Factors on Cognitive Evaluation of the Portuguese Population]. / Fatores Relevantes na Avaliação Cognitiva da População Portuguesa.

INTRODUCTION: Aging is an inevitable process that has a social impact in the forecoming decades, and it will present a great challenge regarding public health. An efficient health system requires a reflection on the preventive measures to be implemented. MATERIAL AND METHODS: The study population comprised a total number of 2672 individuals of both genders, aged 55 years and over, residents in continental Portugal, to whom a questionnaire was applied that included the following sections: Social network; Locomotion; Physical autonomy; Instrumental autonomy; Cognitive assessment; Physical activity. RESULTS: The study of aging in the Portuguese population found that physical autonomy for tasks related to daily life are associated with better cognitive evaluation. A statistically significant association was found between performance in cognitive assessment and gender, age, schooling, the fact of living alone, the number of hours being alone, autonomy to walk in the street, washing, dressing, eating, preparing meals, doing shopping, managing money and taking medications and washer / treat clothing. DISCUSSION: Cognitive evaluation is negatively influenced by the number of hours that an individual is alone. CONCLUSION: Activities of daily life must be valued, since they require the ability to plan and carry out tasks and their preservation is a key component in successful aging.

Introdução: O envelhecimento é um processo inevitável que tem um impacto social e será nas próximas décadas o grande desafio em termos de saúde pública. Um sistema de saúde eficiente requer uma reflexão sobre as medidas preventivas a aplicar. Material e Métodos: A amostra em estudo englobou 2672 indivíduos de ambos os géneros, com idade igual ou superior a 55 anos, residentes em Portugal continental, ao qual foi aplicado um questionário que incluiu as seguintes secções: Rede social; Locomoção; Autonomia física; Autonomia instrumental; Avaliação cognitiva; Atividade física. Resultados: O estudo do perfil de envelhecimento da população Portuguesa revelou que a autonomia física para tarefas relacionadas com o quotidiano, se associam a um melhor desempenho cognitivo. Verificámos uma associação estatisticamente significativa entre o desempenho na avaliação cognitiva e o género, a idade, a escolaridade, o facto de a pessoa viver sozinha, o número de horas que está sozinha, a autonomia a andar na rua, lavar-se, vestir-se, comer, preparar refeições, fazer compras, gerir dinheiro, tomar medicamentos e lavar/tratar a roupa. Discussão: A avaliação cognitiva é influenciada negativamente pelo número de horas que um indivíduo vive sozinho. Conclusão: As atividades da vida diária devem ser valorizadas, uma vez que requerem capacidade para planear e realizar tarefas e a sua preservação é uma componente chave num envelhecimento de sucesso.

Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia.

This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-ß1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with dementia. The recommendations were developed by a multidisciplinary working group based on the available evidence and consensus from focused discussions for (i) identification of Alzheimer's disease (AD) as the cause of dementia, (ii) prediction of rate of decline, (iii) cost-effectiveness, and (iv) interpretation of results. The working group found sufficient evidence to support a recommendation to use CSF AD biomarkers as a supplement to clinical evaluation, particularly in uncertain and atypical cases, to identify or exclude AD as the cause of dementia. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Operational recommendations for the interpretation of ambiguous CSF biomarker results were also provided.

Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.

This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-ß1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.

Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes.

Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., Aß42, total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF Aß42 levels inversely correlated to VV/TIV in the whole study population (Aß42: r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF Aß42 alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF Aß42 levels.

Cerebrospinal fluid Aß40 is similarly reduced in patients with Frontotemporal Lobar Degeneration and Alzheimer's Disease.

Cerebrospinal fluid (CSF) biomarkers have been increasingly studied for dementia diagnosis, however the accuracy to distinguish between different forms of dementia is still unsatisfactory. In this study, the added value of another CSF Aß-peptide (Aß40), along with the core CSF markers t-Tau, p-Tau, and Aß42, in the discrimination between two large dementia groups of Frontotemporal Lobar Degeneration (FTLD; n=107), Alzheimer's Disease (AD; n=107) and non-demented subjects (n=33) was evaluated. In FTLD, t-Tau and p-Tau were significantly increased in relation to controls, but lower than in AD, while Aß42 was similar in FTLD and controls, but higher than in AD. Equally reduced Aß40 levels were seen in both dementia groups, and therefore the combination of Aß40 with core CSF biomarkers optimally discriminated FTLD and AD patients from controls. Aß42 and t-Tau were selected as the best biomarker subset to differentiate FTLD from AD, with no added value of Aß40 to the model. Diagnostic accuracy between FTLD and AD was still sub-optimal, with a significant percentage (23%) of FTLD patients, in particularly women, carrying an ApoE-ε4 allele, showing a CSF-AD biomarkers profile. Although CSF Aß40 does not appear to have an additional value in the distinction between FTLD and AD, it increases the discrimination between subjects with dementia from controls. A CSF-AD biomarker profile can be seen in patients with a clinical phenotype of FTLD, reinforcing the need for autopsy confirmation.

Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers.

INTRODUCTION: Core cerebrospinal fluid (CSF) biomarkers - Aß42, Tau, and phosphorylated Tau (pTau) - have been recently incorporated in the revised criteria for Alzheimer's disease (AD). However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. AIM: In this study, we aim to surpass the efforts from previous studies, by employing a multicenter approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. METHODS: Four different centers participated in this study and followed the same established protocol. CSF samples were analyzed for three biomarkers (Aß42, Tau, and pTau) and tested for different spinning conditions [temperature: room temperature (RT) vs. 4°C; speed: 500 vs. 2000 vs. 3000 g], storage volume variations (25, 50, and 75% of tube total volume), as well as freezing-thaw cycles (up to five cycles). The influence of sample routine parameters, inter-center variability, and relative value of each biomarker (reported as normal/abnormal) was analyzed. RESULTS: Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non-centrifugation or centrifugation at RT, compared to 4°C, led to higher Aß42 levels. Reducing CSF storage volume from 75 to 50% of total tube capacity decreased Aß42 concentration (within analytical CV of the assay), whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to five freeze-thaw cycles, whereas Aß42 levels decrease if CSF is freeze-thawed more than three times. CONCLUSION: This systematic study reinforces the need for CSF centrifugation at 4°C prior to storage and highlights the influence of storage conditions in Aß42 levels. This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-lab variability of CSF-AD biomarkers evaluation.

Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide.

Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for type 2 diabetes (T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors (GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions (e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation (thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2D, stroke and Alzheimer disease (AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential.

Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study.

Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program - Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given.

Vascular, oxidative, and synaptosomal abnormalities during aging and the progression of type 2 diabetes.

Alterations in brain structure and function are a well-known long-term complication of type 2 diabetes (T2D). Although the mechanism(s) by which T2D lead(s) to cognitive dysfunction and neuronal cells degeneration continue(s) to be a matter of debate, vascular alterations emerged as major players in this scenario. This study was aimed to evaluate the antioxidant defenses and oxidative markers present in brain vessels and synaptosomes from 3- and 12-month-old Goto- Kakizaki (GK) rats, a spontaneous non-obese model of T2D, and Wistar control rats. A significant increase in manganese superoxide dismutase (MnSOD) activity and vitamin E levels and a significant decrease in aconitase and glutathione reductase (GR) activities, glutathione (GSH)/glutathione disulfide (GSSG) ratio, and GSH and malondialdehyde (MDA) levels were observed in brain vessels and synaptosomes from GK rats, and these effects were not significantly affected by aging. However, an age-dependent increase in hydrogen peroxide (H2O2) levels in both diabetic synaptosomes and vessels was observed. No significant alterations were observed in the activity of glutathione peroxidase (GPx) and GR in both brain vessels and synaptosomes from diabetic animals. In control rats, an age-dependent increase in the activity of GPx, GR, and MnSOD and vitamin E and MDA levels and an age-dependent decrease in GSH levels were observed in brain vessels. In contrast, a significant age-dependent increase in GSH levels and a decrease in vitamin E levels were observed in synaptosomes from control animals. Altogether, our results show that T2D and aging differently affect brain vessels and synaptosomes. However, both conditions increase the vulnerability of brain structures to degenerative events.

The aging profile of the Portuguese population: a principal component analysis.

In the last 5 years the resident population of Portugal has increased 2.3%, along with a progressive ageing. This study aims assessing the social dependence and frailty, as well as social and familial support needs of the elderly. In an observational, cross-sectional community based study (EPEPP study), a total of 2,672 people, aged 55 or more, were submitted to an enquiry and several variables were studied among three age groups: 55-64 years old (37%), 65-74 years old (37%) and ≥ 75 years old (26%), encompassing a total of 57% women and 43% men. A questionnaire including items such as physical autonomy, locomotion, falls, health/medical complaints, instrumental autonomy, physical activity, health self-evaluation and emotional status was applied. The strong correlations among the studied scores allowed the identification of people groups with common characteristics when a principal component analysis was used: "autonomy" (scores of instrumental autonomy, locomotion and physical autonomy) and "perception of health and emotional status" (scores of health self-evaluation and emotional status), were present in the three age groups. The component analysis evidences that a good autonomy, a good perception of health and emotional status are determinant to a good quality of life in elderly. Although health status and self-rated health have a propensity to deteriorate with aging, older Portuguese consider their state of health satisfactory and tend to underestimate their decline. In what concerns the analysis of gender with the same age and in contrast to what has been reported, older women alike to men, experience a good mobility and health self-evaluation.

Oxidative stress mediates apoptotic effects of ascorbate and dehydroascorbate in human Myelodysplasia cells in vitro.

The Myelodysplastic Syndromes are stem cell heterogeneous disorders characterized by peripheral cytopenias and hypercellular bone marrow, which can evolute to acute leukaemia. Vitamin C can act as an antioxidant, ascorbic acid (AA) donates two electrons and becomes oxidized to dehydroascorbic acid (DHA). Under physiological conditions, vitamin C predominantly exists in its reduced (AA) form but also exists in trace quantities in the oxidized form (DHA). This study evaluates the therapeutic potential of vitamin C in Myelodysplastic Syndromes (MDSs). F36P cells (MDS cell line) were treated with ascorbate and dehydroascorbate alone and in combination with cytarabine. Cell proliferation and viability were assessed by trypan blue assay and cell death was evaluated by optical microscopy and flow cytometry. The role of reactive oxygen species, mitochondrial membrane potential, BAX, BCL-2 and cytochrome C were also assessed. Vitamin C decreases cell proliferation and viability in a concentration, time and administration dependent-manner inducing cell death by apoptosis, which was shown to be associated to an increased in superoxide production, mitochondrial membrane depolarization. These compounds modulate BCL-2, BAX and cytochrome C release. These results suggest that vitamin C induces cell death trough apoptosis in F36P cells and may be a new therapeutic approach in Myelodysplasia.

Amplified and homozygously deleted genes in glioblastoma: impact on gene expression levels.

BACKGROUND: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. METHODOLOGY: Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved. PRINCIPAL FINDINGS: Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%). Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2), while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31) included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. CONCLUSIONS: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.

Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays.

Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas.

A socio-demographic study of aging in the Portuguese population: the EPEPP study.

The increase in life expectancy (LE) observed in Western societies, has resulted in a steep rise of older population. This stresses the importance of the research on aging, to better adequate health and social care organization and improve the quality of life (QoL). The aim of the EPEPP-1 (abbreviated from the Portuguese name: Estudo do Perfil de Envelhecimento da População Portuguesa) study was to characterize the socio-demographic components of the elderly Portuguese population in order to disclose factors that could play a role in the aging process and in the elderly QoL. This observational descriptive study, was performed in 2672 individuals older than 54 years taking into account gender and the residence area (rural vs. urban). A questionnaire about social network (marital status, living alone, the hours spent alone, confidents), and social status (education, occupation) was applied. Social network score revealed significant age and gender trends, women and older people performing worst, but with no difference according to residence area. Almost a third was unmarried and spent eight or more hours per day alone, and a fifth lived alone. Social status revealed that being older female and resident in a rural area quoted worst in the prevalence of illiteracy and undifferentiated occupation. The authors concluded that social isolation, illiteracy and undifferentiated occupation are prevalent in Portuguese older population. Identification of further determinants of isolation, adjustment of procedures to be included in social networks and development of actions directed to education are important fields of intervention influencing the elderly QoL.