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.

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.

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.

Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease.

Alzheimer disease (AD) is a neurodegenerative disease which is characterized by the presence of extracellular senile plaques mainly composed of amyloid-beta peptide (Abeta), intracellular neurofibrillary tangles, and selective synaptic and neuronal loss. AD brains revealed elevated levels of oxidative stress markers which have been implicated in Abeta-induced toxicity. In the present work we addressed the hypothesis that oxidative stress occurs early in the development of AD and evaluated the extension of the oxidative stress and the levels of antioxidants in an in vivo model of AD, the triple-transgenic mouse, which develops plaques, tangles, and cognitive impairments and thus mimics AD progression in humans. We have shown that in this model, levels of antioxidants, namely, reduced glutathione and vitamin E, are decreased and the extent of lipid peroxidation is increased. We have also observed increased activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. These alterations are evident during the Abeta oligomerization period, before the appearance of Abeta plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease.

DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA.

BACKGROUND: Dystonia and parkinsonism may present as part of the same genetic disorder. Identification of the genetic mutations that underlie these diseases may help to shed light on the aetiological processes involved. METHODS: We identified two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. We did autozygosity mapping and candidate gene sequencing in these families. FINDINGS: High-density genome-wide SNP genotyping revealed a disease-segregating region containing 277 homozygous markers identical by state across all affected members from both families. This novel disease locus, designated DYT16, covers 1.2 Mb at chromosome 2q31.2. The crucial interval contains 11 genes or predicted transcripts. Sequence analysis of every exon of all of these transcripts revealed a single disease-segregating mutation, c.665C>T (P222L), in the stress-response gene PRKRA, which encodes the protein kinase, interferon-inducible double-stranded RNA-dependent activator. INTERPRETATION: We describe a mutation within the gene PRKRA that segregates with a novel, autosomal recessive, dystonia parkinsonism syndrome. These patients have progressive, generalised, early-onset dystonia with axial muscle involvement, oromandibular (sardonic smile), laryngeal dystonia and, in some cases, parkinsonian features, and do not respond to levodopa therapy.

ER stress is involved in Abeta-induced GSK-3beta activation and tau phosphorylation.

Intracellular neurofibrillary tangles, one of the characteristic hallmarks of Alzheimer's disease (AD), are mainly composed of hyperphosphorylated tau. The abnormal tau phosphorylation seems to be related to altered activity of kinases such as glycogen synthase kinase-3beta (GSK-3beta). Tau pathology is thought to be a later event during the progression of the disease, and it seems to occur as a consequence of amyloid-beta (Abeta) peptide accumulation. The aim of this work was to investigate whether soluble Abeta1-42, particularly oligomers that correspond to the neurotoxic species involved early in the development of AD, triggers tau phosphorylation by a mechanism involving activation of tau-kinase GSK-3beta. Several studies suggest that GSK-3beta plays a central role in signaling the downstream effects of endoplasmic reticulum (ER) stress. Therefore, the involvement of ER Ca(2+) release in GSK-3beta activation and tau phosphorylation induced by Abeta1-42 oligomers was evaluated using dantrolene, an inhibitor of Ca(2+) release through channels associated with ER ryanodine receptors. We observed that Abeta1-42 oligomers increase tau phosphorylation and compromises cell survival through a mechanism mediated by GSK-3beta activation. We also demonstrated that oligomeric Abeta1-42 induces ER stress and that ER Ca(2+) release is involved in oligomer-induced GSK-3beta activation and tau phosphorylation. This work suggests that GSK-3beta can be a promising target for therapeutic intervention in AD.

Peripheral oxidative damage in mild cognitive impairment and mild Alzheimer's disease.

Oxidative stress has been shown to be a triggering event in the pathogenesis of Alzheimer's disease (AD). However, little evidence exists on the role of oxidative imbalance in Mild Cognitive Impairment (MCI), a group with a high risk of progression to AD. We therefore assessed the peripheral blood levels of a broad spectrum of non-enzymatic and enzymatic antioxidant defenses, as well as lipid and protein oxidation markers and nitrogen oxidative species in 85 MCI patients, 42 mild AD patients and 37 age-matched controls. In mild AD patients, the plasma levels of vitamin E were significantly decreased, while the plasma concentration of oxidized glutathione was increased in both MCI and mild AD patients. An increase in plasmatic and erythrocytes oxidative markers was also observed in MCI and mild AD patients as compared to controls. In both patients groups, increased levels of plasma antioxidants were found in females, whereas apolipoprotein E epsilon4 allele carriers showed higher indices of intracellular oxidative markers. Moreover, in MCI patients, cognitive function positively correlates with antioxidant levels. This study shows that most of the oxidative changes found in mild AD patients are already present in the MCI group, and that progression to AD might be accompanied by antioxidant depletion.

Novel progranulin mutation: screening for PGRN mutations in a Portuguese series of FTD/CBS cases.

Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD) in many families. Different frequencies of these genetic changes have been reported in diverse populations leading us to determine if these mutations were a major cause of FTD in the Portuguese population. The entire coding sequence plus exon 0 of PGRN were sequenced in a consecutive series of 46 FTD/CBS Portuguese patients. Two mutations were found: a novel pathogenic insertion (p.Gln300GlnfsX61) and a previously described point variant (p.T182M) of unclear pathogenicity. Pathogenic mutations in the PGRN gene were found in one of the 36 probands studied (3% of the probands in our series) who had a corticobasal syndrome presentation, indicating that in the Portuguese population, mutations in this gene are not a major cause of FTD.

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.

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.

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.

Prion protein aggregation and neurotoxicity in cortical neurons.

Prion diseases are degenerative disorders of the central nervous system characterized by cerebral protein aggregation and deposition. A cellular glycoprotein, PrP(C) is converted in an altered isoform, PrP(Sc), that accumulates in the brain, and is believed to be responsible for the neuronal loss observed in prion diseases. The synthetic peptide PrP(106-126) shares many characteristics with PrP(Sc) and is largely used to explore the toxic mechanisms underlying prion diseases. In this article we analyzed the neurotoxic effects of PrP(106-126) in primary rat brain cortical neurons, correlating these results with the presence of amyloid plaques in cultures. Incubation of cells with PrP(106-126), 25 muM, for 2 days did not significantly decrease neuronal viability, although we have observed an increase of basal intracellular calcium levels, reactive oxygen species (ROS) formation, and lipid peroxidation. The presence of congophylic and thioflavin S-amyloid-positive plaques in cortical cultures was only observed after a 5-day-treatment period, correlating with a significant decrease of neuronal viability, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) leakage. The data obtained support the idea that PrP(106-126) aggregates in vitro and that the aggregation state is important for its neurotoxicity but also suggest that this synthetic peptide, even when is not aggregated in vitro, can compromise cell homeostasis.

[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.

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.

Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide.

Repeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studied the cytotoxicity in PC12 cells (a dopaminergic neuronal model) chronically and/or acutely exposed to cocaine or amphetamine, as compared to H2O2 exposure. Chronic cocaine treatment induced sensitization to acute cocaine insult and increased cocaine-evoked accumulation of extracellular dopamine, although no changes in dihydroxyphenylacetic acid (DOPAC) levels were observed. Moreover, dopamine was depleted in cells chronically exposed to amphetamine and acute amphetamine toxicity persisted in these cells, indicating that dopamine was not involved in amphetamine cytotoxicity. PC12 cells chronically treated with H2O2 were totally resistant to acute H2O2, but not to acute cocaine or amphetamine exposure, suggesting that the toxicity induced by these stimulant drugs is unrelated to adaptation to oxidative stress. Interestingly, chronic cocaine treatment largely, but not completely, protected the cells against a H2O2 challenge, whilst a decrement in intracellular ATP was observed. This study shows that chronic treatment of PC12 cells with cocaine or H2O2 modifies the cytotoxic response to an acute exposure to these agents.

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.

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.