Abstract Objective This study aimed at investigating a set of peripheral cytokines in elderly female patients with MDD, comparing them to controls, and assessing the potential influence of clinical comorbidities on inflammatory markers. Methods Twenty-five elderly female patients diagnosed with MDD and 19 age-matched female controls were enrolled on this study. Plasma levels of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were evaluated with commercially-available assays. Results Elderly female patients with MDD exhibited higher plasma IL-6 and IL-4 levels when compared to controls. In a logistic regression model taking cytokine levels, comorbidities, and age into account, only type 2 diabetes mellitus (DM2) remained associated with MDD. Conclusion Diabetes influences the association between MDD and higher levels of cytokines in elderly female patients. Future studies should take this evidence into account in order to mitigate confounding factors. markers Twentyfive Twenty five 1 agematched matched IL4, IL4 IL 4, 4 (IL)-4 IL6, IL6 6, 6 IL10, IL10 10, 10 IL-10 IFNγ IFN γ TNFα TNF α commerciallyavailable commercially available assays IL- DM2 DM (DM2 factors (IL)- IL1 IL-1 (DM (IL) (IL

Objective: To compare mortality in older adults with and without mild or moderate cognitive impairment over 15 years of follow-up in a middle-income country, where little information on this subject is available. Methods: A total of 1,281 community-dwelling older adults were followed-up for a median of 13.3 years. We evaluated their cognitive impairment using the Mini-Mental State Examination, categorizing it as none (1.0 SD above cutoff means), mild (1.0 SD below cutoff means) or moderate (2.0 SD below cutoff means). The date of death was determined by reviewing death certificates. Cox’s proportional hazards models were used to evaluate the risk of mortality in participants with cognitive impairment. Results: Participants with mild or moderate cognitive impairment had a higher mortality risk than those without it in the unadjusted model, but these associations did not remain in the final model. After sex stratification, only men with moderate cognitive impairment had a higher mortality risk in the final model. Conclusion: The findings suggest an association between moderate cognitive impairment and all-cause mortality in men in a large Brazilian cohort of older adults.

Objective: A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. Methods: A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman’s rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Results: Plasma IL-17A levels were not statistically different between LLD patients and controls (p = 0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant correlation was observed with cognitive assessments (rho = 0.22, p = 0.01). Conclusion: Our findings do not support an association between plasma IL-17A levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment in LLD patients. If this finding is confirmed in future longitudinal studies, modulation of the T-helper 17 cell (Th17) immune response may be a treatment target for cognitive impairment in this population.

Resumo Um volume crescente de evidências indica que o lúpus eritematoso sistêmico (LES) está associado ao aumento do risco de comprometimento cognitivo e demência. No entanto, até o presente momento nenhum estudo foi conduzido a fim de resumir e avaliar quantitativamente a consistência dos dados. Objetivo: Avaliar quantitativamente a relação entre o LES e anticorpos anticorpos antifosfolípides (aPL) com disfunção cognitiva e demência. Métodos: Toda literatura relevante foi recuperada das bases de dados Pubmed, Scopus e PsycINFO. A meta-análise foi realizada utilizando as estimativas de efeito e os intervalos de confiança de 95% (ICs) para calcular as estimativas de risco combinadas. A heterogeneidade entre os estudos também foi examinada. Resultados: A meta-análise incluiu 11 estudos originais com um total de 81.668 pacientes com demência e 407 pacientes com disfunção cognitiva. Houve associações significativas (modelos de efeitos fixos) entre LES e demência (3 estudos, RR=1,50; IC 95%=1,37-1,64), LES e disfunção cognitiva (4 estudos; OR=2,97; IC 95%=1,72-5,15), e aPL e disfunção cognitiva (5 estudos, OR=1,97; IC 95%=1,55-2,52). Além disso, combinamos os resultados da disfunção cognitiva e demência, uma vez que ambos representaram déficit cognitivo. Houve associações significativas entre aPL e comprometimento cognitivo (6 estudos, OR=2,03, IC 95%=1,62-2,55), e LES e comprometimento cognitivo (7 estudos, OR=1,83; IC 95%=1,42-2,35). Uma heterogeneidade moderada (I2=45,7%) foi encontrada na associação entre LES e comprometimento cognitivo, heterogeneidade baixa (I2=21,8%) na associação entre LES e demência e heterogeneidade quase zero para as outras três principais análises. Conclusão: Tanto o LES como aPL estão associados a déficit cognitivo.

Abstract A growing body of evidence indicates that systemic lupus erythematosus (SLE) is associated with increased risk of cognitive impairment and dementia. However, to date, no studies have been conducted to quantitatively summarize and evaluate the consistency of data. Objective: To quantitatively evaluate the relationship of SLE and antiphospholipid antibodies (aPL) with cognitive dysfunction and dementia. Methods: All relevant literature was retrieved from Pubmed, Scopus, and PsycINFO databases. The meta-analysis was performed using effect estimates and 95% confidence intervals (CIs) to calculate pooled risk estimates. The heterogeneity among studies was also examined. Results: The meta-analysis included 11 original studies involving a total of 81,668 patients with dementia and 407 patients with cognitive dysfunction. There were significant associations on fixed-effect models between SLE and dementia (3 studies; RR=1.50; 95% CI=1.37-1.64), SLE and cognitive dysfunction (4 studies; OR=2.97; 95% CI=1.72-5.15), and aPL and cognitive dysfunction (5 studies, OR=1.97; 95% CI=1.55-2.52). We also combined cognitive dysfunction and dementia outcomes as they both represented cognitive impairment. There were significant associations between aPL and cognitive impairment (6 studies; OR=2.03; 95% CI=1.62-2.55), and SLE and cognitive impairment (7 studies; OR=1.83; 95% CI=1.42-2.35). Moderate heterogeneity (I2=45.7%) was found in the association between SLE and cognitive impairment, low heterogeneity (I2=21.8%) in the association between SLE and dementia, and near zero heterogeneity for the other three main analyses. Conclusion: Both SLE and aPL are associated with cognitive impairment.

Objective: To investigate the moderating effect of an increasing number of clustered metabolic syndrome (MetS) components on the association between MetS and depressive symptoms in a population-based cohort of older adults in Brazil. Methods: This analysis used data from the Bambuí Cohort Aging Study. Participants in this cross-sectional study comprised 1,469 community-dwelling older people aged ≥ 60 years. Analyses were performed to assess both the association between depressive symptoms and each individual MetS component and the association between depressive symptoms and clustering of an increasing number of MetS components. Results: High triglyceride level was the individual component that showed the strongest association with depressive symptoms (odds ratio [OR]: 1.47; 95% confidence intervals [95%CI] 1.19-1.81; p < 0.0001). Only the presence of three MetS components was associated with depressive symptoms (OR = 1.53; 95%CI 1.05-2.23; p = 0.025). No graded association was detected between increasing number of clustered MetS components and depressive symptoms. Conclusions: Increasing the number of MetS components did not impact the association with depressive symptoms. The association between high triglyceride level and depressive symptoms highlights the relevance of lipid metabolism abnormalities for the emergence of depressive symptoms in older adults.

Objective: To determine the sensitivity and specificity of three depression screening scales to diagnose major depressive episodes in the elderly. Methods: Participants (n=129, 88% female) answered a semi-structured psychiatric interview (Mini International Neuropsychiatric Interview) to determine the diagnosis of major depressive disorder. After this, depressive symptoms in depressed and non-depressed subjects were assessed by independent administration of the 15-item Geriatric Depression Scale (GDS-15), Patient Health Questionnaire-9 (PHQ-9), and 17-item Hamilton Rating Scale for Depression (HDRS-17). Results: Patients with major depression and controls did not differ in age and gender distribution. The sensitivity and specificity of all scales to identify a major depressive episode in older adults were ≥ 90%. There were no significant differences between the areas under the curve for PHQ-9 vs. HDRS-17 (z = 1.2, p = 0.2), PHQ-9 vs. GDS-15 (z = 0.26, p = 0.8), or HDRS-17 vs. GDS-15 (z = 1.2, p = 0.2). Conclusion: This study provides evidence supporting the use of PHQ-9 and GDS-15, both of which are simple to administer and easy to interpret, to diagnose major depressive episodes in older adults without neurocognitive disorders.

Objective:Bipolar disorder (BD) is common in clinical psychiatric practice, and several studies have estimated its prevalence to range from 0.5 to 5% in community-based samples. However, no systematic review and meta-analysis of the prevalence of BD type 1 and type 2 has been published in the literature. We carried out a systematic review and meta-analysis of the lifetime and 1-year prevalence of BD type 1 and type 2 and assessed whether the prevalence of BD changed according to the diagnostic criteria adopted (DSM-III, DSM-III-R vs. DSM-IV).Methods:We searched MEDLINE, Scopus, Web of Science, PsycINFO, and the reference lists of identified studies. The analyses included 25 population- or community-based studies and 276,221 participants.Results:The pooled lifetime prevalence of BD type 1 was 1.06% (95% confidence interval [95%CI] 0.81-1.31) and that of BD type 2 was 1.57% (95%CI 1.15-1.99). The pooled 1-year prevalence was 0.71% (95%CI 0.56-0.86) for BD type 1 and 0.50% (95%CI 0.35-0.64) for BD type 2. Subgroup analysis showed a significantly higher lifetime prevalence of BD type 1 according to the DSM-IV criteria compared to the DSM-III and DSM-IIIR criteria (p < 0.001).Conclusion:This meta-analysis confirms that estimates of BD type 1 and type 2 prevalence are low in the general population. The increase in prevalence from DSM-III and DSM-III-R to DSM-IV may reflect different factors, such as minor changes in diagnostic operationalization, use of different assessment instruments, or even a genuine increase in the prevalence of BD.

Objective: Fluid intelligence and the behavioral problems of attention-deficit/hyperactivity disorder (ADHD) are related to academic performance, but how this association occurs is unclear. This study aimed to assess mediation and moderation models that test possible pathways of influence between these factors. Methods: Sixty-two children with ADHD and 33 age-matched, typically developing students were evaluated with Raven's Colored Progressive Matrices and the spelling and arithmetic subtests of the Brazilian School Achievement Test. Dimensional ADHD symptomatology was reported by parents. Results: Our findings suggest that fluid intelligence has a significant impact on academic tests through inattention. The inattentive dimension was the principal behavioral source of influence, also accounting for the association of hyperactive-impulsive manifestations with school achievement. This cognitive-to-behavioral influence path seems to be independent of diagnosis related group, and gender, but lower socioeconomic status might increase its strength. Conclusion: Fluid intelligence is a relevant factor in the influence of ADHD behavioral symptoms on academic performance, but its impact is indirect. Therefore, early identification of both fluid intelligence and inattentive symptoms is of the utmost importance to prevent impaired academic performance and future difficulties in functioning.

Objective: To present a critical review of publications reporting on the rationale and clinical implications of the use of biomarkers for the early diagnosis of Alzheimer's disease (AD). Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012, and based on the following terms: mild cognitive impairment, Alzheimer's disease OR dementia, biomarkers. We retrieved 1,130 articles, of which 175 were reviews. Overall, 955 original articles were eligible. Results: The following points were considered relevant for the present review: a) rationale for biomarkers research in AD and mild cognitive impairment (MCI); b) usefulness of distinct biomarkers for the diagnosis and prediction of AD; c) the role of multimodality biomarkers for the diagnosis and prediction of AD; d) the role of biomarkers in clinical trials of patients with AD and MCI; and e) current limitations to the widespread use of biomarkers in research and clinical settings. Conclusion: Different biomarkers are useful for the early diagnosis and prediction of AD in at-risk subjects. Nonetheless, important methodological limitations need to be overcome for widespread use of biomarkers in research and clinical settings.

Objective: To critically review and evaluate existing knowledge on the conceptual limits and clinical usefulness of the diagnosis of mild cognitive impairment (MCI) and the neuropsychological assessment and short- and long-term prognosis thereof. Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012. Based on the search terms mild cognitive impairment or MCI and epidemiology or diagnosis, we retrieved 1,698 articles, of which 248 were critically eligible (cross-sectional and longitudinal studies); the abstracts of the remaining 1,450 articles were also reviewed. Results: A critical review on the MCI construct is provided, including conceptual and diagnostic aspects; epidemiological relevance; clinical assessment; prognosis; and outcome. The distinct definitions of cognitive impairment, MCI included, yield clinically heterogeneous groups of individuals. Those who will eventually progress to dementia may present with symptoms consistent with the definition of MCI; conversely, individuals with MCI may remain stable or return to normal cognitive function. Conclusion: On clinical grounds, the cross-sectional diagnosis of MCI has limited prognostic relevance. The characterization of persistent and/or progressive cognitive deficits over time is a better approach for identification of cases at the pre-dementia stages, particularly if these cognitive abnormalities are consistent with the natural history of incipient Alzheimer's disease.

CONTEXTO: Deficiência de vitaminas do complexo B tem sido associada a deterioração cognitiva e quadros demenciais em idosos. OBJETIVO: Neste trabalho, foi avaliado se pacientes com doença de Alzheimer (DA) e com comprometimento cognitivo leve (CCL) apresentam níveis séricos de ácido fólico e cobalamina (vitamina B12) menores que idosos controles. MÉTODOS: Foram recrutados 146 idosos (40 com DA, 56 com CCL e 49 idosos controles) para este estudo. Os níveis séricos de ácido fólico e vitamina B12 foram avaliados pelo método de eletroquimioluminescência. RESULTADOS: Os pacientes com DA apresentaram redução estatisticamente significativa nos níveis de ácido fólico em relação aos idosos com CCL e controles (p = 0,02). Esses resultados mantiveram-se estatisticamente significativos após controlar por variáveis sociodemográficas e desempenho cognitivo. Não se observaram diferenças estatisticamente significativas nos níveis de vitamina B12 nem em variáveis hematológicas entre os grupos. CONCLUSÃO: Esses resultados reforçam a importância de anormalidades em aspectos nutricionais, em particular do metabolismo de um-carbono, na fisiopatologia da DA.

BACKGROUND: Complex B vitamin deficiency has been associated to cognitive impairment and dementing disorders in the elderly. OBJECTIVE: This work aims to assess whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) have lower levels of folic acid and cobalamin (vitamin B12) compared to age and gender-matched controls. METHODS: One hundred and forty six elderly subjects (40 AD, 56 MCI and 49 healthy older adults) were recruited for this study. Serum folic acid and vitamin B12 levels were measured by electrochemoluminescence. RESULTS: Compared to MCI and healthy controls a statistically significant reduction in serum concentrations of folic acid in AD patients was found (p = 0.02). This result remained statistically significant after controlling for socio-demographic and cognitive performance variables (p = 0.01). No significant differences were found in serum concentrations of vitamin B12 in patients with AD, MCI and healthy controls. No significant changes in hematologic parameters were observed across these diagnostic groups. DISCUSSION: The present study provides additional evidence that folic acid is reduced in patients with AD and reinforces the importance of nutritional changes, in particular the one-carbon metabolism, in the physiopathology of AD.

OBJETIVO: A identificação de preditores da conversão para a doença de Alzheimer em pacientes com comprometimento cognitivo leve é relevante para o manejo clínico e para decidir sobre a prescrição de drogas antidemência. MÉTODO: Estudo longitudinal em coorte de indivíduos idosos com comprometimento cognitivo leve amnéstico e controles saudáveis; estimativa do risco da progressão para doença de Alzheimer nos dois grupos; determinação das variáveis preditivas desse desfecho. RESULTADOS: Pacientes com comprometimento cognitivo leve amnéstico apresentaram maior risco de desenvolver doença de Alzheimer ao longo do seguimento (odds ratio = 4,5, CI95% [1,3-13,6], p = 0,012). Na avaliação inicial, idade mais avançada, escores mais baixos nos testes cognitivos e do alelo APOE*4 foram preditores da conversão do comprometimento cognitivo leve amnéstico para doença de Alzheimer. Em uma subamostra de pacientes com comprometimento cognitivo leve amnéstico, aqueles que progrediram para doença de Alzheimer tinham concentrações liquóricas mais baixas do peptídeo beta-amilóide (Aβ42, p = 0,020) e mais altas da proteína TAU total (p = 0,030) e TAU fosforilada (p = 0,010) do que os pacientes que não progrediram para doença de Alzheimer. DISCUSSÃO: Este é o primeiro estudo brasileiro com biomarcadores liquóricos a relatar preditores da conversão comprometimento cognitivo leve-doença de Alzheimer. Nossos dados biológicos (aumento de TAU total e fosfo-TAU; redução de Aβ42), e podem auxiliar na identificação dos pacientes com comprometimento cognitivo leve com maior risco de evolução para demência.

OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.

OBJECTIVE: To determine the accuracy of the Mini-Mental State Examination combined with the Verbal Fluency Test and Clock Drawing Test for the identification of patients with mild cognitive impairment and Alzheimer's disease (AD). METHOD: These tests were used to evaluate cognitive function in 247 older adults. Subjects were divided into three groups according to their cognitive state: mild cognitive impairment (n=83), AD (n=81), cognitively unimpaired controls (n=83), based on clinical and neuropsychological data. The diagnostic accuracy of each test for discriminating between these diagnostic groups (mild cognitive impairment or AD vs. controls) was examined with the aid of Receiver Operating Characteristic (ROC) curves. Additionally, we evaluated the benefit of the combination of tests on diagnostic accuracy. RESULTS: Although they were accurate enough for the identification of Alzheimer's disease, neither test alone proved adequate for the correct separation of patients with mild cognitive impairment from healthy subjects. Combining these tests did not improve diagnostic accuracy, as compared to the Mini-Mental State Examination alone, in the identification of patients with mild cognitive impairment or Alzheimer's disease. CONCLUSIONS: The present data do not warrant the combined use of the Mini-Mental State Examination, the Verbal Fluency Test and the Clock Drawing Test as a sufficient diagnostic schedule in screening for mild cognitive impairment. The present data do not support the notion that the combination of test scores is better that the use of Mini-Mental State Examination scores alone in the screening for Alzheimer's disease.