Search

The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

Objectives In 2012, Kamboh and colleagues published a genome-wide association study that identified the DCHS2 gene (rs1466662 T/A) influencing the age at onset of Alzheimer's disease (AD). We aimed to investigate if there is association between the DCHS2 gene and amnestic mild cognitive impairment (aMCI) and AD in a sample of the Brazilian population. Methods 143 controls, 79 aMCI and 299 AD patients were selected and submitted to the same protocol of tests. Genotyping was performed using the Real Time PCR Results Amnestic MCI patients showed a higher prevalence of AA than controls and a lower frequency of TT when compared with controls. We also stratified the sample according to the APOE e4 status. No difference in DCHS2 genotype or allelic frequency occurred in the APOE e4 allele carrier subgroup. Amnestic MCI patients showed a higher frequency of AA genotype and a lower frequency of TA and TT when compared with controls in APOE e4 allele non-carrier subgroup. The allelic distribution followed the same pattern. In AD group, we observed a significant difference with a higher A allelic frequency in AD in this subgroup. A multiple logistic regression demonstrated that in APOE e4 non-carriers, allele rs1466662 was associated to aMCI group. Different variables were associated with aMCI and AD according to APOE e4 status in our sample. Low level of education was associated with AD, while diabetes mellitus type 2 was associated with aMCI. Copyright © 2016 John Wiley & Sons, Ltd. Conclusions Our findings suggest a possible role for DCHS2 gene in aMCI and AD.

The scope of this study was to assess the prevalence and factors associated with frailty among the elderly in Primary Health Care. It is a cross-sectional study carried out with 1750 elderly people in the Southeast of Brazil. The Brazilian Older American Resources and Services Multidimensional Functional Assessment Questionnaire (BOMFAQ) and the Clinical-Functional Vulnerability Index (CFVI) were used for data collection. Descriptive and bivariate analyzes were performed, followed by Poisson regression analysis, with robust variance, to obtain adjusted prevalence ratios (PR). The CFVI identified 357 frail elderly people (20.1%). The variables that remained statistically associated with frailty after multiple analysis were: single/widowed (PR = 1.05; 95%CI = 1.02-1.07); four years of schooling (PR = 1.05; 95%CI = 1.03-1.08); polypathology (PR = 1.05; 95%CI = 1.01-1.09); polypharmacy (PR = 1.21; 95%CI = 1.17-1.26); mental disorder (PR = 1.16; 95%CI = 1.12-1.21); cognitive impairment (PR = 1.71; 95%CI = 1.57-1.86); Daily Living Activity impairment (PR = 1.12; 95%CI = 1.09-1.14); falls (PR = 1.06; 95%CI = 1.03-1.10); hospitalization (PR = 1.39; 95%CI = 1.27-1.52); urinary incontinence and self-perception of health. The conclusion that a significant prevalence of frailty in the study reaffirms the need for a multidimensional approach to the elderly.Objetivou-se conhecer a prevalência e os fatores associados à fragilidade em idosos na Atenção Primária à Saúde. Trata-se de estudo transversal realizado com1750 idosos no Sudeste do Brasil. Utilizou-se para coleta o Brazilian Older Americans Resources and Services MultiDimensional Function Assessment Questionnaire (BOMFAQ) e o Índice de Vulnerabilidade Clínico-funcional (IVCF-20). Realizaram-se as análises descritivas e bivariadas, seguidas da análise regressão de Poisson, com variância robusta, para obtenção de razões de prevalência ajustadas. O IVCF-20 identificou 357 idosos frágeis (20,1%). As variáveis estatisticamente associadas à fragilidade após análise múltipla foram: estado civil (RP = 1,05; IC95% = 1,02-1,07), escolaridade (RP = 1,05; IC95% = 1,03-1,08), polipatologia (RP = 1,05; IC95% = 1,01-1,09), polifarmácia (RP = 1,21; IC95% = 1,17-1,26), transtorno mental (RP = 1,16; IC95% = 1,12-1,21), comprometimento cognitivo (RP = 1,71; IC95% = 1,57-1,86), comprometimento de atividades de vida diária (RP = 1,12; IC95% = 1,09-1,14), quedas (RP = 1,06; IC95% = 1,03-1,10), internação (RP = 1,39; IC95% = 1,27-1,52) e incontinência urinária, autopercepção da saúde. Concluiu-se que a significante prevalência de fragilidade do estudo reitera a necessidade de abordagem multidimensional do idoso.

Previous studies suggest that executive functions influence the performance on visuoconstructional tasks. This study aims to investigate whether the relationship between planning ability and the copy of complex figures is mediated by distinct components of executive functions (i.e., working memory, inhibitory control and cognitive flexibility). We included a 129 older adults with Alzheimer’s disease (n=36, AD), mild cognitive impairment (MCI, n=67), and with no evidence of cognitive impairment (controls, n=26). We evaluated the mediation effect of planning abilities, working memory, cognitive flexibility and inhibitory control on visuoconstructional tasks using a multiple mediation models. We found a significant direct effect of planning on visuoconstructional abilities and a partial mediation effect of working memory and cognitive flexibility on visuoconstructional abilities. The present results indicate that the performance on visuoconstructional task is mediated by multiple interrelated executive functions components, in particular working memory and cognitive flexibility. (JINS, 2015, 21, 392–398)

Background:Evidences suggest thatGAB2andBDNFgenes may be associated with Alzheimer's disease (AD). We aimed to investigate theGAB2rs2373115 andBDNFrs6265 polymorphisms and the risk of AD in a Brazilian sample.Methods:269 AD patients and 114 controls were genotyped with Real-time PCR. Multifactor dimensionality reduction (MDR) was employed to explore the effects of gene–gene interactions.Results:GAB2andBDNFwere not associated with AD in our sample. NeverthelessBDNFVal allele (rs6265) presented a synergic association with theAPOEε4 allele. A multiple logistic regression demonstrated that theAPOEε4 allele and years of education were the best predictors for AD. In ε4 non-carriers sex, education and hypertension were independently correlated with AD, while in ε4 carriers we did not observe any association. The findings were further confirmed by bootstrapping method.Conclusions:Our data suggest that the interaction ofBDNFandAPOEhas significant effect on AD. Moreover in absence of ε4, female sex, low level of education and hypertension are independently associated with AD. Interventions aimed to prevent AD should focus on these factors and also taking into account theAPOEalleles.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Neurotrophic factors and inflammatory markers may play considerable roles in AD. In this study we measured, through Enzyme-Linked Immunosorbent Assay, the plasma levels of brain derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and neuronal growth factor (NGF), as well as tumor necrosis factor-alpha soluble receptors, sTNFR1 and sTNFR2, and soluble intercellular adhesion molecule 1 (sICAM-1), in 50 AD patients, 37 patients with mild cognitive impairment (MCI) and 56 healthy elderly controls. BDNF levels, expressed as median and interquartile range, were higher for AD patients (2545.3, 1497.4–4153.4 pg/ml) compared to controls (1503.8, 802.3–2378.4 pg/ml), P

Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia.

Summary Objective: Translate, transcultural adaptation and application to Brazilian Portuguese of the Alzheimer’s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale as a cognitive screening instrument. Method: We applied the back translation added with pretest and bilingual methods. The sample was composed by 95 elderly individuals and their caregivers. Thirty-two (32) participants were diagnosed as mild cognitive impairment (MCI) patients, 33 as Alzheimer’s disease (AD) patients and 30 were considered as cognitively normal individuals. Results: There were only little changes on the scale. The Cronbach alpha coefficient was 0.89. The scores were 72.9 for control group, followed by MCI (65.1) and by AD (55.9), with a p-value < 0.001. The ROC curve value was 0.89. We considered a cut point of 72 and we observed a sensibility of 86.2%, specificity of 70%, positive predictive value of 86.2%, negative predictive value of 70%, positive likelihood ratio of 2.9 and negative likelihood ratio of 0.2. Conclusion: ADCS-ADL scale presents satisfactory psychometric properties to discriminate between MCI, AD and normal cognition. Resumo Objetivo: Tradução, adaptação transcultural para o português brasileiro e aplicação da escala Alzheimer’s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) como instrumento de triagem cognitiva. Método: Retrotradução associada ao método bilíngue e de pré-teste. A amostra foi constituída por 95 idosos e seus respectivos acompanhantes, sendo 30 controles, 32 portadores de comprometimento cognitivo leve (CCL) e 33 portadores de demência de Alzheimer (DA) em fase inicial. Resultados: Um pequeno número de modificações ocorreu na escala. O coeficiente alpha de Cronbach foi 0,89. O grupo controle pontuou 72,9, seguido pelo CCL (65,1) e pelo DA (55,9), valor p

Higher risk of dementia is expected for patients with late onset depression (LOD) history. The IL-10 polymorphisms are associated with Alzheimer disease (AD). On the other hand, there is no study associating IL-10 polymorphisms to LOD. This study aimed to investigate the -1082G/A polymorphism association in LOD, AD patients and controls and also the peripheral expression of IL-10 in CD4+ T cells. It was done in a case-control study comparing immune system phenotype and genetic polymorphism association among control individuals, LOD and AD patients. Participants were 569 subjects composed the genetics sample (249 AD, 222 LOD and 98 controls) from a tertiary medical center based on Belo Horizonte, Brazil. Flow cytometry analysis was performed in 55 people (22 AD patients, 11 LOD patients and 22 controls). A real time PCR for IL-10 SNP (rs 1800896) through genotyping analysis and flow cytometry evaluation of CD4+ T cells expressing IL-10 was done. An increased CD4+ T cells expressing IL-10 were detected only in the AD group. There was no difference detected in allele or genotype analysis for IL-10 polymorphism among LOD, AD patients or controls. IL-10 might have a role in the modulation of immune response in AD patients, however it is not presented in LOD population.

Objectives Examine the association between polymorphisms in the AKT1 and AKTIP genes and late-onset depression (LOD). Major depressive disorder is one of the most prevalent neuropsychiatric diseases. LOD is a disorder that starts after 65 years old. AKT1 is a downstream enzyme that has been implicated in the pathogenesis of neurotransmitter-related disorders, such as depression. The identification of a novel AKT1-binding protein (AKTIP) was pointed as an important new target. AKTIP binds directly to AKT1, enhancing the phosphorylation of regulatory sites, and this modulation are affected by AKT1 activation. The association of AKT1 and AKTIP polymorphisms with depressive symptoms was not investigated in LOD. Design Genotype tagSNPs in the AKT1 and AKTIP in LOD patients and controls. Settings An academic medical center. Participants Sample composed by 190 outpatients with LOD and 77 healthy individuals. Measures The participants were evaluated using Diagnostic and Statistical Manual IV criteria, MINI-PLUS and the Geriatric Depression Scale. Results Our findings suggested an association between the tagSNP rs3730358 homozygous A/A (p = 0.006) and LOD. A strong association of allele A and increased association for LOD was demonstrated with tagSNP rs3730358 (p-value = 0.003). Limitations Limitation include composition of our control group, where the exclusion criteria generated a kind of super-healthy older group what might have produced a hidden stratification when compared with the LOD. Conclusion This study is the first one to establish the association of the AKT1/AKTIP genes and LOD, and further studies are necessary to clarify the functional role of these proteins. Copyright © 2013 John Wiley & Sons, Ltd.

OBJETIVO: Analisar o perfil clínico e a atividade autonômica de pacientes com diagnóstico de doença de Alzheimer ou demência mista (DM). MÉTODOS: Foram avaliados 54 pacientes com indicação de uso de inibidores da colinesterase, por meio de exame clínico, de eletrocardiograma de repouso e da análise espectral da variabilidade da frequência cardíaca (VFC). RESULTADOS: A casuística estudada, constituída por 61,1% de mulheres, apresentava média de 77,1 anos de idade, 3,3 anos de escolaridade, pontuação de 16,4 no miniexame do estado mental e intervalo médio de 26,2 meses entre o início dos sintomas e o diagnóstico. A quase totalidade (90,7%) apresentava comorbidades, com o uso, em média, de 3,7 drogas/paciente. Trinta e um (57,4%) pacientes apresentavam alterações eletrocardiográficas e nove (16,6%), hipotensão ortostática (HO). Esta apresentou associação com o diagnóstico de DM (p = 0,001) e com valores mais baixos dos componentes de baixa (BF) e de alta (AF) frequência da VFC na posição supina (p = 0,000 e p = 0,017), além de valores médios menores de BF em ortostatismo (p = 0,006). O diagnóstico de DM se associou a menores valores de BF nas duas posições (p = 0,003 e p = 0,007). CONCLUSÃO: Na amostra estudada, a presença de comorbidades e o uso de vários fármacos foram frequentes. Foram observados sinais de disfunção autonômica, resultando em HO, principalmente nos pacientes com DM. OBJECTIVE: To analyze the clinical and autonomical profile of patients with Alzheimer's disease or mixed dementia (MD). METHODS: Fifty-four patients with indication for cholinesterase inhibitors usewere evaluated through clinical examination, rest electrocardiogram, and spectral analysis of heart rate (HR) variability through digital Holter system recordings. RESULTS: Overall, 61.1% of patients were female and were, on average, 77.1 years of age, 3.3 years of schooling and scored 16.4 points on the Mini Mental State Examination. The gap between symptom onset and diagnosis was 26.2 months. Almost all patients (90.7%) presented at least one clinical comorbidity, and each patient took, on average, 3.7 drugs to control them. Thirty-one patients had some alteration on the electrocardiogram and nine (16.6%) had orthostatic hypotension (OH). The latter was associated with the diagnosis of MD (p = 0.001), with lower values of low (LF) and high (HF) frequency components of the spectral analysis in the supine position (p = 0.000 and p = 0.017, respectively) and with lower values of LF in the orthostatic position (p = 0.006). Diagnosis ofMDwas associated with lower values of LF in both positions (p = 0.003 and p = 0.007). CONCLUSION: This sample of patients had frequent comorbidities, which resulted in the prescription of multiple drugs. Signs of autonomic dysfunction resulting in OH were found mainly in those with MD.

Background:The assessment of visuospatial abilities is usually performed by drawing tasks. In patients with very low formal education, the use of these tasks might be biased by their cultural background. The Stick Design Test was developed for the assessment of this population. We aim to expand the test psychometric properties by assessing its construct, criterion-related and ecological validity in older adults with low formal education.Method:Healthy older adults (n = 63) and Alzheimer's disease patients (n = 92) performed the Stick Design Test, Mini-Mental State Examination, Digit Span Forward and the Clock Drawing Test. Their caregivers answered Personal Care and Instrumental Activities of Daily Living). Construct validity was assessed by factor analysis, convergent correlations (with the Clock Drawing Test), and divergent correlations (with Digit Span Forward); criterion-related validity by receiver operating characteristic curve analysis and binary logistic regression; and Ecological validity by correlations with ADL.Results:The test factor structure was composed by one component (R2 = 64%). Significant correlations with the Clock Drawing Test and Digit Span Forward were found, and the relationship was stronger with the first measure. The test was less associated with formal education than the Clock Drawing Test. It classified about 76% of the participants correctly and had and additive effect with the Mini-Mental State Examination (84% of correct classification). The test also correlated significantly with measures of ADL, suggesting ecological validity.Conclusions:The Stick Design Test shows evidence of construct, criterion-related and ecological validity. It is an interesting alternative to drawing tasks for the assessment of visuospatial abilities.

OBJETIVO: Este estudo avaliou a associação entre as doenças crônico-degenerativas e o declínio funcional, a cognição e a predição da mortalidade. MÉTODOS: Um estudo transversal foi realizado em um Serviço de Geriatria em Belo Horizonte, Brasil, envolvendo 424 pacientes subdivididos em dois grupos: controle e com demência. Foram analisados dados sociodemográficos e ambientais, doenças crônicas degenerativas, o Índice de Charlson, dados sobre a demência, funcionais e de cognição. RESULTADOS: Após análise univariada, houve maior frequência de acidente vascular encefálico (AVE), incontinência urinária, constipação intestinal e distúrbio do sono no grupo demência, enquanto na análise multivariada houve maior número de fatores ambientais e distúrbio do sono. Quanto ao Mini Exame do Estado Mental (MEEM), pacientes com doença pulmonar obstrutiva crônica (DPOC), AVE e insuficiência cardíaca apresentaram escores mais baixos. Em relação ao Índice de Charlson, houve maior pontuação no grupo com demência. CONCLUSÃO: As comorbidades foram associadas ao declínio funcional nos idosos com demência. OBJECTIVE: To assess the association between chronic degenerative diseases and functional decline, cognition, and mortality prediction. METHODS: A cross-sectional study was conducted in a geriatrics service in Belo Horizonte, Brazil, involving 424 patients subdivided into two groups: control and dementia. The study analyzed socio-demographic and environmental data, chronic degenerative diseases, the Charlson index, and data on functional and cognitive dementia. RESULTS: After a univariate analysis, there was a greater frequency of cerebrovascular accident (CVA), urinary incontinence, constipation, and sleep disorder in the dementia group, while the multivariate analysis showed a greater number of environmental factors and sleep disorder. Regarding the Mini Mental State Examination (MMSE), patients with chronic obstructive pulmonary disease (COPD), CVA, and heart failure presented lower scores. There was a greater score in the dementia group with regarding the Charlson index. CONCLUSION: These comorbidities were associated with the functional decline in elderly people with dementia.

Life expectancy in Brazil has increased markedly over the last 30 years. Hence, age-related disorders, such as Alzheimer's disease (AD), warrant special attention due to their high prevalence in the elderly. Pharmacologic treatment of AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest clinical benefits both in the short and long-term. However, clinical response is heterogeneous and needs further investigation. Objective: To investigate the rate of response to ChEI in AD after three months of treatment. Methods: Patients with mild or moderate dementia due to probable AD or to AD associated with cerebrovascular disease were included in the study. The subjects were assessed at baseline and again after three months of ChEI treatment. Subjects were submitted to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire, Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good response was defined by a gain of ≥2 points on the MMSE after three months of treatment in relation to baseline. Results: Seventy-one patients, 66 (93%) with probable AD and five (7%) with AD associated with cerebrovascular disease, were evaluated. The good response rate at three months was 31.0%, being 37.2% and 21.4% in mild and moderate dementia, respectively. There were no significant differences on most tests, except for improvement in hallucinations, agitation and dysphoria in moderate dementia patients. Conclusion: The rate of good clinical response to ChEI was higher than usually reported. Specific behavioral features significantly improved in the subgroup of moderate dementia. RESUMO A expectativa de vida no Brasil aumentou significativamente nos últimos 30 anos. Desse modo, transtornos relacionados à idade, como a doença de Alzheimer (DA), merecem especial atenção, devido à elevada prevalência. O tratamento farmacológico da DA se baseia nos inibidores da colinesterase (IChE) e na memantina, com melhora modesta em curto e longo prazo. Entretanto, a resposta clínica é heterogênea e necessita maior investigação. Objetivo: Investigar a taxa de resposta aos IChE em pacientes com DA após três meses de tratamento. Métodos: Pacientes com demência leve ou moderada devida à DA ou DA com doença cerebrovascular foram avaliados antes e após três meses de uso de IChE. Todos foram submetidos ao Mini-Exame do Estado Mental (MEEM), Escala de Demência Mattis, avaliação das atividades básicas de vida diária de Katz, Questionário de Pfeffer, Inventário Neuropsiquiátrico e Escala de Depressão de Cornell. Boa resposta foi definida pelo ganho de ≥2 pontos no MEEM em relação à primeira consulta, após três meses. Resultados: Setenta e um pacientes, 66 (93%) com DA provável e cinco (7%) com DA associada à doença cerebrovascular, foram avaliados. A taxa de boa resposta clínica em três meses foi de 31.0%, sendo 37,2% e 21,4% na demência leve e moderada, respectivamente. Não houve diferença significativa na maioria dos testes, exceto para melhora de alucinação, agitação e depressão em pacientes com demência moderada. Conclusão: A taxa de boa resposta clínica aos IChE foi superior à encontrada na literatura. Observou-se melhora de alguns sintomas comportamentais em pacientes com DA moderada.

Introduction: The Frontal Assessment Battery (FAB) is a for the assessment of executive functions. We investigated its validity and reliability and proposed normative data in a representative sample of older adults. Method: 391 healthy elderly subjects and 93 Alzheimer’s disease (AD) patients performed the FAB. Internal consistency, convergent correlations, ROC curve and logistic regression were used to assess its psychometric properties. Results: We found good internal consistency, significant correlations with other tests and moderate accuracy (64%) for AD diagnosis. The use of specific subtests increased diagnostic potential (75%). Normative data stratified by age and education were proposed. Conclusion: The FAB showed adequate psychometric properties. The normative values stratified by age and education can improve its clinical use for neuropsychological assessment.

Objective Depression might be a prodromal stage of dementia. Many factors contribute to the etiology of depression and dementia, being inflammation one of those. The present work measured and analyzed immune molecules involved in the innate immunity on cluster of differentiation 14 (CD14+) monocytes trying to investigate any relationship among late-onset depression (LOD) and Alzheimer's disease (AD). Methods Immune molecules were evaluated in monocytes of AD, LOD patients, and controls using flow cytometry. Results Interestingly, interleukin 1 beta (IL-1β) expressing CD14+ monocytes were increased in AD patients compared with controls. LOD presented intermediate frequency of CD14+ monocytes expressing IL-1β between controls and AD patients. Conclusion Results suggest that an increased frequency of CD14+ monocytes expressing IL-1β level could be a stage marker related to the pathophysiology of dementia process between normal aging and AD. Copyright © 2013 John Wiley & Sons, Ltd.

As the proportion of population above age 65 grows, so too increases the prevalence of those individuals who are obese. This phenomenon of an elderly population with obesity is the source of much research and debate with regards to treatment recommendations. It appears that older individuals on the extreme ends of the BMI spectrum, those who are underweight and those who are morbidly obese, have an increased risk of mortality. One major concern in the treatment of obese, elderly individuals is that many may have sarcopenic obesity which can be worsened with weight loss where some degree of lean body mass loss is inevitable. While various methods of weight loss may be recommended in some elderly who are obese, it is clear that any chosen method should be accompanied by a resistance training program in order to preserve muscle mass. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG .

Objectives: This study aims to evaluate the association between polymorphisms in circadian genes and Alzheimer’s disease (AD) and/or late-onset depression (LOD). AD pathology leads to circadian disturbances, with clear negative influence on quality of life. In addition, there is an increasing evidence that regulators of circadian system have effects on AD and LOD pathology. Design and Subjects: An exploratory case-control study designed to evaluate SNPs in the PER2, PER3, CLOCK and OX2R genes in a sample composed by 249 AD, 222 LOD and 112 healthy individuals. Measures: The participants were evaluated using DSM-IV criteria for LOD and NINCDS-ADRDA for AD. Results: In allelic analysis, the OX2R SNP, rs2134294, showed an association of allele C with LOD (p =0.02, OR= 1.6) and AD (p=0.04, OR =1.5). The rs2134294 also showed a genotypic association C/C (p =0.01) for higher risk to develop LOD compared to the control group, with an odd’s ratio of 2.7. The rs9370399 (OX2R) has also shown an association between A allele (p=0.03, OR= 1.4) and AD. These results do not persist after a 1,000 permutations test. For other markers of the OX2R gene and for all other markers of this study no association was found. Conclusion: In conclusion, the present study found that the investigated Circadian Genes (PER2, PER3, CLOCK and OX2R) polymorphisms were not associated with LOD or AD.

Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded β-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well.

Objective Alzheimer's disease (AD) has a multifactorial etiology involving an interaction of genetic and environmental factors. The Apolipoprotein E e4 (ApoE e4) is the single most important genetic risk factor for sporadic AD. Our aim was to study the association between sociodemographic, clinical data and gene polymorphisms in patients with sporadic AD in a heterogeneous genomic Brazilian population with low educational levels. Methods We selected 169 sporadic AD patients and 97 controls older than 65 years and compared co-variables between them: age, years of education, vascular risk factors, genomic ancestry, and functional polymorphisms of ApoE, BDNF, COMT, and 5-HTTLPR. We also determined the genomic ancestry of all individuals. Results The average years of education was significantly smaller in the patient's group (p = 0.003), and they had a history of depression when compared with controls (p

Recent finding suggests that in Amnestic Mild Cognitive Impairment (MCI) executive functions deficits may be a frequent clinical finding. Automatic and Controlled attentional processes are related to the allocation of cognitive resources in different stimuli, being important to executive functioning. The present study aims at assessing the hypothesis of executive dysfunction deficits in MCI patients. Method: forty five MCI patients and forty five normal aging controls (NC) were assessed with the Five Digits Test (5D), a Mini-Verbal test version of the Stroop Test. Group comparisons were performed by t tests and the non-parametric Mann-Whitney test. Results: comparisons indicates significant differences between NC and MCI in efficiency measures of controlled attentional processes, with moderate effect sizes, but not in automatic attentional processes or processing speed. Conclusion: the present work shows a selective pattern of impairment in MCI, indicating specific deficits in executive functioning with spared processing speed.

Alzheimer's disease (AD) is characterized by impairment in memory and autonomy, causing excessive pressure on family and an overburdened health care system. Early diagnosis, with the appropriate treatment, is important to reduce the pattern of disease progression. Objective: The study sought to identify the most probable causes of delay in diagnosis. Methods: A cross-sectional study involving AD patients followed at an Outpatient Geriatric Clinic from a tertiary public university hospital was conducted between June 2009 and February 2011. Results: Ninety-four patients were evaluated (66% women), aged 77.76±6.8 years and with median educational level of 3 years (95% CI 2.7-3.80). Regarding severity of dementia, 51.8% of patients were classified as having mild dementia (CDR 1), 40% moderate dementia (CDR 2) and 8.2% severe dementia (CDR 3). Mean educational level of caregivers was 8.3±3.9 years. Among those who believed there was a delay, 36% stated that the "family thought that the changes were normal for the age of the patient" reporting average delay of 1.8 years (95% CI: 1.3-2.5) while 45.3% stated that the "doctor did not reach a diagnosis" reporting a median delay of 1.5 years (95% CI: 1.4-2.3). Conclusion: Based on these results, it can be concluded the time between onset of symptoms and diagnosis was excessive. This study may be useful to help increase awareness of issues not sufficiently discussed in the literature, such as diagnostic delay and influence of caregivers' educational level on treatment. Resumo A doença de Alzheimer é caracterizada por comprometimento na memória e na autonomia, causando pressão excessiva em familiares e sobrecarregando o sistema público de saúde. O diagnóstico precoce, com o tratamento adequado, é importante para reduzir o padrão de evolução da doença. Objetivo: O estudo pretende identificar as causas mais prováveis de atraso no diagnóstico. Métodos: Trata-se de um estudo transversal envolvendo pacientes com DA acompanhados em Ambulatório de Geriatria de um hospital terciário público entre junho de 2009 e fevereiro de 2011. Resultados: Noventa e quatro pacientes foram avaliados (66% mulheres), com média de idade de 77,8±6,8 anos e com mediana de escolaridade de 3 anos (IC 95%: 2,7-3,8). Quanto à gravidade da doença, 51,8% foram classificados como demência leve (CDR 1), 40% como demência moderada (CDR 2) e 8,2% como demência grave (CDR 3). A escolaridade do cuidador foi de 8,3±3,9 anos. Entre aqueles que acreditavam que havia um atraso no diagnóstico, 36% responderam que "a família achava as alterações como normais para a idade do paciente", com média de 1,8 anos (IC 95%: 1,3-2,5) e 45,3% responderam que "o médico não fez o diagnóstico", com mediana de 1,5 anos (IC 95%: 1,4-2,3). Foi observado que o tempo entre o início dos sintomas e o diagnóstico foi maior do que deveria ser. Conclusão: Este estudo pode contribuir para aumentar o conhecimento sobre questões ainda pouco discutidas na literatura científica, como atraso no diagnóstico e influência da escolaridade do cuidador no tratamento.

In 2012, Kamboh and colleagues published a genome-wide association study that identified the DCHS2 gene (rs1466662 T/A) influencing the age at onset of Alzheimer's disease (AD). We aimed to investigate if there is association between the DCHS2 gene and amnestic mild cognitive impairment (aMCI) and AD in a sample of the Brazilian population.143 controls, 79 aMCI and 299 AD patients were selected and submitted to the same protocol of tests. Genotyping was performed using the Real Time PCR RESULTS: Amnestic MCI patients showed a higher prevalence of AA than controls and a lower frequency of TT when compared with controls. We also stratified the sample according to the APOE ε4 status. No difference in DCHS2 genotype or allelic frequency occurred in the APOE ε4 allele carrier subgroup. Amnestic MCI patients showed a higher frequency of AA genotype and a lower frequency of TA and TT when compared with controls in APOE ε4 allele non-carrier subgroup. The allelic distribution followed the same pattern. In AD group, we observed a significant difference with a higher A allelic frequency in AD in this subgroup. A multiple logistic regression demonstrated that in APOE ε4 non-carriers, allele rs1466662 was associated to aMCI group. Different variables were associated with aMCI and AD according to APOE ε4 status in our sample. Low level of education was associated with AD, while diabetes mellitus type 2 was associated with aMCI. Copyright © 2016 John WileySons, Ltd.Our findings suggest a possible role for DCHS2 gene in aMCI and AD.

Cognitive functioning influences activities of daily living (ADL). However, studies reporting the association between ADL and neuropsychological performance show inconsistent results regarding what specific cognitive domains are related to each specific functional domains. Additionally, whether depressive symptoms are associated with a worse functional performance in older adults is still under explored. We investigated if specific cognitive domains and depressive symptoms would affect different aspects of ADL. Participants were 274 older adults (96 normal aging participants, 85 patients with mild cognitive impairment, and 93 patients probable with mild Alzheimer’s disease dementia) with low formal education (∼4 years). Measures of ADL included three complexity levels: Self-care, Instrumental-Domestic, and Instrumental-Complex. The specific cognitive functions were evaluated through a factorial strategy resulting in four cognitive domains: Executive Functions, Language/Semantic Memory, Episodic Memory, and Visuospatial Abilities. The Geriatric Depression Scale measured depressive symptoms. Multiple linear regression analysis showed executive functions and episodic memory as significant predictors of Instrumental-Domestic ADL, and executive functions, episodic memory and language/semantic memory as predictors of Instrumental-Complex ADL (22 and 28% of explained variance, respectively). Ordinal regression analysis showed the influence of specific cognitive functions and depressive symptoms on each one of the instrumental ADL. We observed a heterogeneous pattern of association with explained variance ranging from 22 to 38%. Different instrumental ADL had specific cognitive predictors and depressive symptoms were predictive of ADL involving social contact. Our results suggest a specific pattern of influence depending on the specific instrumental daily living activity.

This study evaluated barriers to access to treatment for Alzheimer's disease based on administrative cases involving cholinesterase inhibitors (ChEIs) and submitted to the Minas Gerais State Health Secretariat in Brazil in 2012 and 2013. Drawing on data from 165 randomly selected cases, the study addressed the following dimensions of access: geographic accessibility, accommodation, acceptability, availability, and affordability. The administrative processing to supply ChEIs took an average of 39 days and was influenced by characteristics of the path taken by the user. The majority of the prescribers met less than 80% of the required criteria in the Clinical Protocol and Therapeutic Guidelines (CPTG) for Alzheimer's disease. As a result, 38% of requests for medication were denied. Private treatment with ChEIs cost the equivalent of 21 days of the monthly minimum wage. In conclusion, bureaucratic administrative procedures and prescribers' difficulty in following the CPTG hindered access to treatment of Alzheimer's disease and imposed a heavy burden on patients' pockets.

Background Naturalistic studies evaluate individuals in their usual way of living, presenting more "real-life" data regarding patients and their diseases. Objective To investigate demographic, clinical, and genetic factors that could be predictive of good response to cholinesterase inhibitors (ChEI) treatment in Alzheimer's disease (AD) and AD + cerebrovascular disease (CVD). Patients and methods A total of 129 patients were diagnosed with AD or AD + CVD and with mild-to-moderate dementia. After a 12-month treatment, 97 patients completed the study. They were evaluated at baseline and after three, six, and 12 months of ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6 polymorphisms were determined for all of the participants. In each visit, we used cognitive, functional, mood, and behavior scales. We classified patients according to their scores in the Mini-Mental State Examination (MMSE). Good responders were defined as those scoring ≥2 in the MMSE at 12 months. Results The rate of good clinical response was 27.8%. In a longitudinal analysis, the patients with mild AD and also good responders at three months were considered to be good responders at 12 months. There was no correlation between ChEI dose, APOE and CYP2D6 polymorphisms, and the pattern of clinical response. Conclusion A higher rate of good response was observed in this study compared to that in previous investigations. The pharmacogenetic aspects do not seem to have an influence in the response.

Introduction: elderly people with mild cognitive impairment (CCL) manifest difficulties in performing daily living activities (AVD), however, there are difficulties related to identification and classification of impaired activities. Objective: to assess whether there is evidence in the literature of AVD impairment in older adults with CCL. Methods: literature review based on search in the PUBMED and LILACS databases using the keywords: “mild cognitive impairment” AND “activities of daily living” and their correlates in Portuguese and Spanish that resulted in 759 publications. Repeated studies, reviews, validation, editorials, and guidelines studies, and letters to the editor and commentaries were excluded. Clinical trials, descriptive, comparative, and cohorts studies in English, Spanish, and Portuguese, published up to 2012 were selected, whose main objective was to investigate AVD in older adults with CCL. The inclusion criteria were met by 41 studies for this review. Results: clinical, cognitive, and functional variables were measured. There was variation in the sample Functional decline in elderly people with mild cognitive impairment Fabiana Carla Matos da Cunha1, Marco Tulio Gualberto Cintra2, Joalce Magalhaes Dornelas3, Marcella Guimaraes Assis4, Janine Gomes Cassiano5, Rodrigo Nicolato6, Leandro Fernandes Malloy-Diniz7, Edgar Nunes de Moraes8, Maria Aparecida Camargos Bicalho9 1 Terapeuta Ocupacional. Mestre em Neurociencias. Hospital Sao Judas Tadeu. Ribeirao das Neves, MG – Brasil. 2 Medico. Mestre em Saude do Adulto. Hospital das Clinicas da Universidade Federal de Minas Gerais-UFMGInstituto Jenny de Andrade Faria de Atencao a Saude do Idoso. Belo Horizonte, MG-Brasil. 3 Medica. Faculdade de Medicina da UFMG. Belo Horizonte, MG – Brasil. 4 Terapeuta Ocupacional. Doutora. Professora titular do Departamento de Terapia Ocupacional, da Escola de Educacao Fisica, Fisioterapia e Terapia Ocupacional, da UFMG. Belo Horizonte, MG – Brasil. 5 Terapeuta Ocupacional. Doutora. Professora Adjunta do Departamento de Terapia Ocupacional da UFMG. Belo Horizonte, MG – Brasil. 6 Medico. Doutor. Professor adjunto de Psicologia Medica do Departamento de Saude Mental da Faculdade de Medicina da UFMG. Belo Horizonte, MG – Brasil. 7 Psicologo. Doutor. Professor Adjunto do Departamento de Saude Mental da Faculdade de Medicina da UFMG. Belo Horizonte, MG – Brasil. 8 Medico. Doutor. Professor Associado do Departamento de Clinica Medica da Faculdade de Medicina da UFMG. Belo Horizonte, MG – Brasil. 9 Medica. Doutora. Professora adjunta do Departamento Clinica Medica e pesquisadora da Faculdade de Medicina da UFMG. Belo Horizonte, MG – Brasil. Declinio funcional em idosos com comprometimento cognitivo leve DOI: 10.5935/2238-3182.20150081

Introduction: Great efforts have been made to develop diagnostic methods for precisely screen patients with mild cognitive impairment (MCI) who will progress to dementia. Many biomarkers have been studied for that. However, their high costs, small availability and need for invasive procedures sometimes make these biomarkers of limited usefulness. With the advantages of its low cost and being non-invasive, the P300 evoked potential (EP) is one methods under investigation. Objective: To assess whether the P300 evoked potential can estimate the risk of MCI progression to Alzheimer’s dementia (AD). Methods: Review of the PubMed database using the descriptors: “evoked potentials”, “Alzheimer’s disease” and “mild cognitive impairment”. Results: We selected eight among 929 articles after applying the exclusion criteria. From the articles we concluded that the electrode placed at the parietal region is the most effective and that the latency increase and amplitude decrease of the electrode reading are related to the higher risk of progression from MCI to a diagnosis of AD. Most of the selected studies sustain P300 EP to estimate the progression risk from MCI to AD. However, the low number of studies, small sample size and heterogeneous results are pointed as important limitations. Conclusion: The P300 represents a promising method to estimate the likelihood of the MCI progression to AD. However, more studies are needed to support P300 for daily clinical practice.

Objectives The objectives of this study were to assess demographic trends of a long-term care institution (LTCI) for the aged throughout 24 years and to discuss the results considering regulations and demographic, socioeconomic, and epidemiological changes in Brazil during this period. Methods We assessed administrative data of 394 residents of a Brazilian LTCI between January 1, 1990, and December 31, 2013. We calculated age at admission, age at death, length of stay (LOS), and median age of the residents on December 31 for each year from 1990 to 2013. Annual mortality index and total number of admissions and discharges also were analyzed. We used the Jonckheere-Terpstra trend test and 1-way ANOVA for statistical analysis. Results We observed a significant statistical increased trend of the mean age at admission, of the median age of the residents, and of the median LOS throughout the period. There was no increased or decreased trend of the median age at death. Conclusions The increased trend of the mean age at admission and the median age of the residents may reflect improvements in health, socioeconomic status, life expectancy, and the development of protective regulations for older adults in Brazil. The increased trend of the median LOS may reflect the aforementioned improvements, but we expect a future inversion of this trend due to the admission of older, sicker, and more functionally dependent elderly individuals.

The article aims to describe the profile of elderly victims of falls and traffic accidents from the data of the Surveillance Survey of Violence and Accidents (VIVA). The VIVA Survey was conducted in the emergency health-services of the Unified Health System in the capitals of Brazil in 2011. The sample of elderly by type of accident was subjected to the two-step cluster procedure. Of the 2463 elderly persons in question, 79.8% suffered falls and 20.2% were the victims of traffic accidents. The 1812 elderly who fell were grouped together into 4 clusters: Cluster 1, in which all had disabilities; Cluster 2, all were non-white and falls took place in the home; Cluster 3, younger and active seniors; and Cluster 4, with a higher proportion of seniors 80 years old or above who were white. Among cases of traffic accidents, 446 seniors were grouped into two clusters: Cluster 1 of younger elderly, drivers or passengers; Cluster 2, with higher age seniors, mostly pedestrians. The main victims of falls were women with low schooling and unemployed; traffic accident victims were mostly younger and male. Complications were similar in victims of falls and traffic accidents. Clusters allow adoption of targeted measures of care, prevention and health promotion.

Objective: To propose and evaluate the psychometric properties of a multidimensional measure of activities of daily living (ADLs) based on the Katz and Lawton indices for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: In this study, 85 patients with MCI and 93 with AD, stratified by age (≤ 74 years, > 74 years), completed the Mini Mental State Examination (MMSE) and the Geriatric Depression Scale, and their caregivers completed scales for ADLs. Construct validity (factor analysis), reliability (internal consistency), and criterion-related validity (receiver operating characteristic analysis and logistic regression) were assessed. Results: Three factors of ADL (self-care, domestic activities, and complex activities) were identified and used for item reorganization and for the creation of a new inventory, called the General Activities of Daily Living Scale (GADL). The components showed good internal consistency (> 0.800) and moderate (younger participants) or high (older participants) accuracy for the distinction between MCI and AD. An additive effect was found between the GADL complex ADLs and global ADLs with the MMSE for the correct classification of younger patients. Conclusion: The GADL showed evidence of validity and reliability for the Brazilian elderly population. It may also play an important role in the differential diagnosis of MCI and AD.

The semantic verbal fluency task is broadly used in the neuropsychological assessment of elderly subjects. Even some studies have identified differences in verbal fluency clustering and switching measures between subjects with normal aging and a clinical condition such as Mild Cognitive Impairment (MCI) and Alzheimer’s disease, the results are not always consistent. This study aimed to compare clustering and switching measures of an animal’s semantic verbal fluency task among normal controls (n=25), amnestic Mild Cognitive Impairment (aMCI; n=25), amnestic multiple domain Mild Cognitive Impairment (a+mdMCI; n=25) and Alzheimer’s disease (AD; n=25) Brazilian subjects. The analyses were executed considering three (unifying the MCI subtypes) and four groups. As the data were not normally distributed, we carried out non-parametric tests (Kruskal-Wallis and Mann-Whitney tests) to evaluate the differences in performance in the measures of the verbal fluency test among the groups. The comparison demonstrated that the groups differed in the total of correct words produced, number of clusters and switching but the measure of new subcategories was the only with significant difference among the NC and all the clinical groups. The measure of new subcategories is the number of original subcategories inside the higher category of animals that the subject produced, such as farm, domestic, African animals. Our results indicate that semantic memory impairment is a visible and recent deficit that occurs even in non-demented subjects with very mild cognitive impairment and the implications of theses findings are discussed.

No Brasil, a distribuição etária do tétano é pouco estudada. Neste trabalho foi analisada a evolução histórica do coeficiente de mortalidade por tétano no Brasil, entre 1980 e 1991, e estabelecida a distribuição dos casos pela faixa etária, tendo por base o Sistema de Informações de Mortalidade. Os coeficientes de mortalidade por faixa etária foram calculados conforme os dados fornecidos pela FUNASA-CENEPI, DATASUS e IBGE. Utilizou-se o teste qui-quadrado para comparar os coeficientes de mortalidade para as diversas faixas etárias, por ano e região do país. Houve declínio dos coeficientes de mortalidade em todas as faixas etárias, exceto nos idosos. Nas regiões Norte e Sul houve aumento do coeficiente de mortalidade nos idosos. No Brasil, o tétano vem apresentando comportamento epidemiológico semelhante ao observado nos países desenvolvidos, onde os idosos representam o principal grupo de risco para adoecer e morrer da doença. Epidemiological data regarding the age distribution of tetanus in Brazil is scarce. This work analyzed the historical evolution of tetanus in Brazil, between 1980 and 1991, according to the Mortality Information System and established the age distribution for this disease. The data used was that provided by FUNASA-CENEPI, DATASUS and IBGE. Between 1980 and 1991, the coefficient of general incidence dropped from 2.6 to 1.0 case per 100,000 inhabitants. There was a decline in the mortality coefficients within all the age groups, except in the elderly. In the North and South regions, there was an increase in the mortality coefficient among the elderly. Infantile tetanus is disappearing, particularly, in the developed areas. However, the overall lethality tended to rise in this period and, in 1991, it reached 32.5%. In Brazil, tetanus presents epidemic behavior similar to that observed in the developed countries, where the elderly represent the main risk group to contract and die from the disease.

Objective Depressive pseudodementia (DPD) is a clinical condition characterized by depressive symptoms followed by cognitive and functional impairment characteristics of dementia. Memory complaints are one of the most related cognitive symptoms in DPD. The present study aims to assess the verbal learning profile of elderly patients with DPD. Methods Ninety-six older adults (34 DPD and 62 controls) were assessed by neuropsychological tests including the Rey auditory-verbal learning test (RAVLT). A multivariate general linear model was used to assess group differences and controlled for demographic factors. Results Moderate or large effects were found on all RAVLT components, except for short-term and recognition memory. Conclusion DPD impairs verbal memory, with large effect size on free recall and moderate effect size on the learning. Short-term storage and recognition memory are useful in clinical contexts when the differential diagnosis is required. Objetivo A pseudodemência depressiva (PDD) é uma condição clínica onde sintomas depressivos são acompanhados por comprometimento cognitivo e funcional característicos da demência. Queixas de memória são um dos sintomas mais comumente relatados na PDD. O presente estudo almeja investigar a aprendizagem verbal de pacientes idosos com PDD. Método 96 idosos (34 PDD e 62 controles) realizaram testes neuropsicológicos incluindo o Teste de Aprendizagem Auditivo-Verbal de Rey (RAVLT). Adotou-se um modelo linear geral multivariado para comparação dos grupos controlando variáveis sociodemográficas. Resultados Pacientes com PDD apresentaram déficits em todo o RAVLT, com exceção no armazenamento de curto-prazo e reconhecimento, com tamanhos de efeito moderados ou altos. Conclusão A PDD compromete a memória verbal mais intensamente na evocação livre e de forma moderada na aprendizagem. A memória de curto-prazo e de reconhecimento são úteis em contextos onde o diagnóstico diferencial é necessário.

(CFT-T) in screening Alzheimer’s disease (AD). Methods:We administered the CFT (animal category) and the Mini Mental Status Examination (MMSE) to 235 mild AD patients and their age-, genderand educationmatched Mild Cognitive Impairment (MCI) patients and cognitively normal elderly controls (NC). We developed a composite score for screening AD comprised of weighted sub-index scores of CFT (first-half response, second-half response, perseverative error, intrusion error, switching score and clustering score) and demographic characteristics. W eighting coefficients were estimated by stepwise and forward selection method of logistic regression analysis. We compared the diagnostic accuracies among the CFT-C, CFT-T and MMSE using receiver operator curve analysis. Results: The weighted composite index was calculated using the logit of test scores weighted by their coefficients from logistic regression models:logit (case) 1⁄4 5.541 -0.0303 age 0.1133 gender + 0.062 3 education level 0.179 3 first-half score 0.1863 second-half score0.472 3 switching score 0.185 3 clustering score + 0.4973 perseveration score. The area under the ROC (AUC) of the CFT-C for diagnosing AD was .837 (SE 1⁄4 .018, 95% CI1⁄4 .801-.872), which was smaller than that of the MMSE (AUC 1⁄4 .889, SE 1⁄4 .015, 95% CI 1⁄4 .860.918) but larger than that of the CFT-T (AUC 1⁄4 .801, SE 1⁄4 .020, 95% CI 1⁄4 .762-.841). The AUC of the CFT-C for diagnosing MCI (AUC 1⁄4 .623, SE 1⁄4 .026, 95% CI 1⁄4 .572-.673) was significantly larger than that of the MMSE (AUC 1⁄4 .467, SE 1⁄4 .027, 95% CI 1⁄4 .414-.519) and the CFT-T (AUC 1⁄4 .576, SE 1⁄4 .026, 95% CI 1⁄4 .524-.628). These results were consistently replicated in 100 bootstrapped re-samples. Conclusions: The CFT can be a good alternative to the MMSE in screening AD and MCI if we use its weighted composite score instead of total score.

Examine the association between polymorphisms in the AKT1 and AKTIP genes and late-onset depression (LOD). Major depressive disorder is one of the most prevalent neuropsychiatric diseases. LOD is a disorder that starts after 65 years old. AKT1 is a downstream enzyme that has been implicated in the pathogenesis of neurotransmitter-related disorders, such as depression. The identification of a novel AKT1-binding protein (AKTIP) was pointed as an important new target. AKTIP binds directly to AKT1, enhancing the phosphorylation of regulatory sites, and this modulation are affected by AKT1 activation. The association of AKT1 and AKTIP polymorphisms with depressive symptoms was not investigated in LOD.Genotype tagSNPs in the AKT1 and AKTIP in LOD patients and controls.An academic medical center.Sample composed by 190 outpatients with LOD and 77 healthy individuals.The participants were evaluated using Diagnostic and Statistical Manual IV criteria, MINI-PLUS and the Geriatric Depression Scale.Our findings suggested an association between the tagSNP rs3730358 homozygous A/A (p = 0.006) and LOD. A strong association of allele A and increased association for LOD was demonstrated with tagSNP rs3730358 (p-value = 0.003).Limitation include composition of our control group, where the exclusion criteria generated a kind of super-healthy older group what might have produced a hidden stratification when compared with the LOD.This study is the first one to establish the association of the AKT1/AKTIP genes and LOD, and further studies are necessary to clarify the functional role of these proteins.

Background and objectivesThe neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use.Methods and resultsA protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living.ConclusionThe study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education.

Introducao: Estudos naturalisticos sobre Doenca de Alzheimer, os quais avaliam individuos em sua forma habitual de vida, sem seleciona-los previamente, mostrando-os com suas comorbidades e diferentes idades, sao raros no Brasil. Objetivos: Este trabalho objetiva investigar os fatores demograficos, clinicos e geneticos que podem ser preditivos de boa resposta ao tratamento com os inibidores da colinesterase (IChE) na doenca de Alzheimer (DA) e DA + doenca cerebrovascular (DCV); medir a concentracao plasmatica de donepezila em pacientes em uso da medicacao; verificar a correlacao entre a concentracao de donepezila com os polimorfismos do gene Apoliproteina E (APOE) e do gene CYP2D6, bem como com a resposta clinica. Pacientes e Metodos: De um total de 129 pacientes diagnosticados com DA ou DA + DCV, com demencia leve a moderada, 97 pacientes completaram o estudo apos 12 meses de seguimento e foram avaliados no inicio, apos tres, seis e 12 meses de uso de IChE (donepezila, galantamina ou rivastigmina). A genotipagem da APOE foi determinada para todos os participantes e os polimorfismos da CYP2D6 para aqueles que fizeram uso da donepezila. Em cada visita, foram administradas escalas de avaliacao cognitiva, funcional, de humor e de comportamento, bem como medida a concentracao plasmatica de donepezila nas ultimas 3 visitas. Os pacientes foram classificados de acordo com a pontuacao no Mini-Exame do Estado Mental (MEEM). Bons respondedores foram definidos como aqueles que pontuaram 2 no MEEM em 12 meses em relacao ao MEEM da primeira consulta. Resultados: A taxa de boa resposta clinica foi de 27,8%. Metade destes pacientes eram carreadores do alelo APOE4. Na analise longitudinal, os pacientes com DA leve e tambem os pacientes que pontuaram 2 no MEEM aos tres meses apresentaram maior chance de serem bons respondedores aos 12 meses. A resposta clinica a donepezila foi investigada em razao da concentracao da droga no plasma e pela frequencia dos polimorfismos da APOE e CYP2D6 em 42 pacientes que fizeram uso da medicacao (dose de 10 mg) durante 12 meses. Nao houve correlacao entre polimorfismos da APOE, da CYP2D6 e o padrao de resposta clinica. No entanto, os bons e neutros respondedores tiveram maior concentracao plasmatica de donepezila aos 12 meses de tratamento em relacao aos tres e seis meses, sugerindo haver melhor resposta com concentracoes mais elevadas da droga. Conclusao: Os principais fatores preditivos de boa resposta a estas drogas aos 12 meses de tratamento foram a gravidade leve da demencia e a presenca de boa resposta aos tres meses de uso da medicacao. Nao houve correlacao entre polimorfismo da APOE, da CYP2D6 e o padrao de resposta clinica na populacao estudada. A concentracao plasmatica de donepezila foi maior nos bons e neutros respondedores.

Cholinesterase inhibitors (ChEIs), the mainstay treatment for dementia, have systemic actions that can affect cardiovascular and autonomic nervous system (ANS). Thirty-nine patients with Alzheimer´s disease or mixed dementia underwent a comprehensive clinical evaluation, prior to and during ChEIs therapy, including orthostatic challenge, electrocardiogram (EKG) and heart rate variability (HRV) spectral analysis through Holter recordings. ChEIs therapy determined a decrease in supine diastolic blood pressure (BP) and in both diastolic and systolic BP in orthostatic position (79.8 ± 9.0 vs. 76.4 ± 9.3 mmHg, p=0.012; 79.9 ± 11.6 vs. 75.3 ± 9.9, p=0.005 and 144.6 ± 25.8 vs. 137.6 ± 21.1, p=0.020, respectively). Spectral analysis revealed no difference on static HRV components, but, during orthostatic challenge, an increase in LF/HF ratio (2.2±2.4 vs. 4.6±5.9, p=0.011) and a reduction in HF component emerged (1604.3 ± 5610.1 vs. 266.1 ± 525.5, p=0.010). ChEIs showed no influence on EKG parameters or on the occurrence of orthostatic hypotension. Treatment with ChEIs was associated with functional improvement of the ANS behavior and to a decrease in supine DBP and in both orthostatic SBP and DBP.

To analyze the clinical and autonomical profile of patients with Alzheimer's disease or mixed dementia (MD).Fifty-four patients with indication for cholinesterase inhibitors use were evaluated through clinical examination, rest electrocardiogram, and spectral analysis of heart rate (HR) variability through digital Holter system recordings.Overall, 61.1% of patients were female and were, on average, 77.1 years of age, 3.3 years of schooling and scored 16.4 points on the Mini Mental State Examination. The gap between symptom onset and diagnosis was 26.2 months. Almost all patients (90.7%) presented at least one clinical comorbidity, and each patient took, on average, 3.7 drugs to control them. Thirty-one patients had some alteration on the electrocardiogram and nine (16.6%) had orthostatic hypotension (OH). The latter was associated with the diagnosis of MD (p=0.001), with lower values of low (LF) and high (HF) frequency components of the spectral analysis in the supine position (p=0.000 and p=0.017, respectively) and with lower values of LF in the orthostatic position (p=0.006). Diagnosis of MD was associated with lower values of LF in both positions (p=0.003 and p=0.007).This sample of patients had frequent comorbidities, which resulted in the prescription of multiple drugs. Signs of autonomic dysfunction resulting in OH were found mainly in those with MD.