Neuropsychiatric Symptoms of Alzheimer's Disease in Down Syndrome and Its Impact on Caregiver Distress.

BACKGROUND: Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. OBJECTIVE: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). METHODS: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). RESULTS: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2 = 0.627, F(15,76) = 8.510, p < 0.001). CONCLUSION: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome.

There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (≥30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Informant-reported behaviors related to frontal lobe dysfunction were found to correlate negatively with executive function performance. Disinhibition and executive dysfunction were associated with the clinical stage of dementia. The odds of having Alzheimer's disease increased in parallel with increases in the domain and total Frontal Systems Behavior Scale scores (p ≤ 0.5). Disinhibition, executive dysfunction and apathy should be taken into consideration during the clinical evaluation of adults with DS, and future studies should consider the intersection of neuropathology, brain connectivity, and behavior.

Cognitive screening test in primary care: cut points for low education.

OBJECTIVE: To establish the diagnostic accuracy of the Brazilian version of the General Practitioner Assessment of Cognition (GPCOG-Br) compared to the Mini-Mental State Examination (MMSE) in individuals with low educational level. METHODS: Ninety-three patients (≥ 60 years old) from Brazilian primary care units provided sociodemographic, cognitive, and functional data. Receiver operating characteristics, areas under the curve (AUC) and logistic regressions were conducted. RESULTS: Sixty-eight patients with 0-4 years of education. Cases (n = 44) were older (p = 0.006) and performed worse than controls (n = 49) on all cognitive or functional measures (p < 0.001). The GPCOG-Br demonstrated similar diagnostic accuracy to the MMSE (AUC = 0.90 and 0.91, respectively) and similar positive and negative predictive values (PPV/NPV, respectively: 0.79/0.86 for GPCOG-Br and 0.79/0.81 for MMSE). Adjusted cut-points displayed high sensitivity (all 86%) and satisfactory specificity (65%-80%). Lower educational level predicted lower cognitive performance. CONCLUSIONS: The GPCOG-Br is clinically well-suited for use in primary care.

Cognitive screening test in primary care: cut points for low education

ABSTRACT OBJECTIVE To establish the diagnostic accuracy of the Brazilian version of the General Practitioner Assessment of Cognition (GPCOG-Br) compared to the Mini-Mental State Examination (MMSE) in individuals with low educational level. METHODS Ninety-three patients (≥ 60 years old) from Brazilian primary care units provided sociodemographic, cognitive, and functional data. Receiver operating characteristics, areas under the curve (AUC) and logistic regressions were conducted. RESULTS Sixty-eight patients with 0-4 years of education. Cases (n = 44) were older (p = 0.006) and performed worse than controls (n = 49) on all cognitive or functional measures (p < 0.001). The GPCOG-Br demonstrated similar diagnostic accuracy to the MMSE (AUC = 0.90 and 0.91, respectively) and similar positive and negative predictive values (PPV/NPV, respectively: 0.79/0.86 for GPCOG-Br and 0.79/0.81 for MMSE). Adjusted cut-points displayed high sensitivity (all 86%) and satisfactory specificity (65%-80%). Lower educational level predicted lower cognitive performance. CONCLUSIONS The GPCOG-Br is clinically well-suited for use in primary care.

Psychotic symptoms in older people without dementia from a Brazilian community-based sample: A seven years' follow-up.

BACKGROUND: Studies of the incidence of psychotic symptoms in elderly people at risk of dementia are scarce. This is a seven year follow up study aiming to determine the incidence of psychotic symptoms and their correlation with other clinical aspects, in particular the rate of development of cognitive impairment. METHODS: Cohort study of a community-based sample of elderly subjects. At study entry in 2004, the sample was composed of 1,125 individuals aged 60 years and older. Of this total, 547 subjects were re-evaluated in 2011 and submitted to the original study protocol. Of these, 199 showed no psychotic symptoms at phase I, while 64 already had psychotic symptoms in 2004. RESULTS: The incidence of at least one psychotic symptom in the 7 year period was 8.0% (Visual/tactile hallucinations: 4.5%; Persecutory delusions: 3.0%; Auditory hallucinations: 2.5%). Development of psychotic symptoms was associated with epilepsy (OR: 7.75 and 15.83), lower MMSE (OR: 0.72) and reported depression (OR: 6.48). A total of 57.8% of individuals with psychotic symptoms developed cognitive impairment after 7 years. Visual/tactile hallucinations were the only psychotic symptom predictive of this impairment, which was related to lower MMSE and greater functional impairment. CONCLUSIONS: The incidence of psychotic symptoms and the conversion rate to cognitive impairment was in the upper range when compared with previous reports. Visual/tactile hallucinations were the most frequent symptoms and were predictive of cognitive impairment over the 7 year period. A significant relationship was found between the incidence of psychotic symptoms and low MMSE scores, as well as clinical comorbities such as epilepsy, reported depression, diabetes and syphilis.

Depression in Women with Recurrent Miscarriages - an Exploratory Study.

Objective To assess depression, domestic violence and the use of substances in women with recurrent miscarriages. Methods The Abuse Assessment Screen (AAS), the Edinburgh Postnatal Depression Scale (EPDS) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were used to assess violence, depression and the use of substances among women with recurrent miscarriages. The population corresponded to patients receiving prenatal care from June to August 2014. Multiple logistic regression was used to assess the multivariable relationship between depression and sociodemographic, psychosocial and medical characteristics (p < 0,10). Results The prevalence of depression was of 41.3% (95% confidence interval [CI] = 28.3-55.7%). One third of the pregnant women (32.6%) reported emotional or physical violence, and 13% were classified as abusing or addicted to tobacco according to ASSIST. History of psychiatric diseases was associated with depression (p = 0.005). Violence during life demonstrated a modest association (p = 0.073) with depression, as well as the number of miscarriages (p = 0.071). Conclusion Depression is a frequent disease among pregnant women with recurrent miscarriages. The results of this investigation suggest that a systematic assessment of depression and its associated conditions, such as domestic violence and the use of substances, should be part of the prenatal follow-up visits for women with recurrent miscarriages.

Depression in Women with Recurrent Miscarriages - an Exploratory Study / Depressão em mulheres com perdas gestacionais recorrentes - um estudo investigativo

ABSTRACT Objective: To assess depression, domestic violence and the use of substances in women with recurrent miscarriages. Methods: The Abuse Assessment Screen (AAS), the Edinburgh Postnatal Depression Scale (EPDS) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were used to assess violence, depression and the use of substances among women with recurrent miscarriages. The population corresponded to patients receiv-ing prenatal care from June to August 2014. Multiple logistic regression was used to assess the multivariable relationship between depression and sociodemographic, psychosocial and medical characteristics (p < 0,10). Results: The prevalence of depression was of 41.3% (95% confidence interval [CI] 1/4 28.3-55.7%). One third of the pregnant women (32.6%) reported emotional or physical violence, and 13% were classified as abusing or addicted to tobacco according to ASSIST. History of psychiatric diseases was associated with depression (p 1/4 0.005). Violence during life demonstrated a modest association (p 1/4 0.073) with depression, as well as the number of miscarriages (p 1/4 0.071). Conclusion: Depression is a frequent disease among pregnant women with recurrent miscarriages. The results of this investigation suggest that a systematic assessment of depression and its associated conditions, such as domestic violence and the use of substances, should be part of the prenatal follow-up visits for women with recurrent miscarriages.

RESUMO Objetivo: Avaliar a presença de depressão, violência doméstica e uso de substâncias em gestantes com história de perdas gestacionais de repetição. Métodos: Foram utilizados os instrumentos: Edinburgh Postnatal Depression Scale (EPDS), Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), Abuse Assessment Screen (AAS), além de um questionário com dados sociodemográficos e clínicos elaborado pelos investigadores. As variáveis que apresentaram associação com depressão na análise bivariada (p < 0,10), tais como número de abortos e violência durante a vida, entraram no modelo de regressão logística. Resultados: Foram entrevistadas 46 pacientes, sendo encontrada uma prevalência de depressão de 41,3% (intervalo de confiança [IC] de 95% 1/4 28,3-55,7%). Com relação à violência contra a mulher, um terço das gestantes (32,6%) foi vítima de violência emocional ou física pelo seu parceiro ou por alguém próximo a elas. O abuso e/ou dependência de tabaco estava presente em 13% das gestantes, segundo o ASSIST. Na análise bivariada, observou-se uma associação significativa entre histórico de doença psiquiátrica e depressão em mulheres com abortamento de repetição (p 1/4 0,005). Observamos também uma tendência de associação entre depressão, número de abortos (p 1/4 0,071) e histórico de violência durante a vida (p 1/4 0,073) . Conclusão: Depressão é uma doença frequente entre as gestantes com abortamento de repetição. A sobreposição entre depressão, violência doméstica e uso de substâncias aponta para a necessidade do rastreio sistemático dessas condições no pré-natal de gestantes com perdas gestacionais de repetição.

The Geriatric Anxiety Inventory in primary care: applicability and psychometric characteristics of the original and short form

Abstract Background Generalized anxiety disorder (GAD) has negative implications for people’s lives, but is often underdiagnosed in the elderly. There is a shortage of instruments to assess geriatric anxiety. Objectives To analyze the applicability and psychometric properties of the Portuguese version of the Geriatric Anxiety Inventory (GAI) and its short form (GAI-SF) within primary care. Methods Fifty-five seniors were classified as non-demented by a multidisciplinary panel. The protocol included the GAI, the Self-Reporting Questionnaire (SRQ-20), the Depression Scale D-10, Mini-Mental State Examination (MMSE), Bayer Scale for Activities of Daily Living (B-ADL) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A sub-sample also completed the Beck Anxiety Inventory (BAI). Results The GAI and GAI-SF showed good internal consistency (0.89; 0.62, respectively) and test-retest stability (0.58, 0.97). The GAI and GAI-SF correlated significantly with the SRQ-20 (0.74, 0.55) and BAI (0.75, 0.58). Discussion The psychometric characteristics of the Brazilian versions of the GAI and GAI-SF suggest these instruments are suitable for application in the Brazilian elderly population within the primary care setting.

Metamemory and aging: Psychometric properties of the Brazilian version of the Multifactorial Memory Questionnaire for elderly / Metamemória e envelhecimento: propriedades psicométricas da versão brasileira do questionário multifatorial de memória para idosos

ABSTRACT Metamemory measures provide subjective memory information and are relevant to investigate memory ability in aging. However, there is a lack of metamemory instruments available in Brazil. Objective: The aim of this study was to examine the psychometric properties of the Brazilian version of the Multifactorial Memory Questionnaire (MMQ), which evaluates different dimensions of subjective memory functioning, such as Feelings, Abilities and Strategies used in everyday life. Methods: The MMQ was translated into Portuguese and administered to 30 Brazilian elderly subjects. The participants underwent cognitive tests, mood scales and metamemory instruments. Results: Analyses revealed good internal consistency (Cronbach's a coefficient ranged from 0.75 to 0.89) and test-retest validity for each MMQ dimensions (positive correlations between two applications ranged from 0.75 to 0.8). Convergent validity evidence for the MMQ was confirmed by significant positive correlations (0.47 to 0.68) with dimensions of the Metamemory in Adulthood scale (MIA) (i.e., the Ability, Control, Self-efficacy and Strategy dimensions). Discriminant validity revealed no associations between the MMQ and cognitive performance, suggesting a weak metamemory-objective memory correspondence. Moreover, there was a negative correlation between MMQ-Ability subscale scores and mood symptoms (-0.63 for anxious symptoms, and -0.54 for depressive symptoms); and the Brazilian MMQ was comparable with MMQ translations to other languages. Conclusion: The Brazilian MMQ exhibits good psychometric properties and appears promising for clinical and research purposes. Additional studies are needed to further examine the psychometric properties of the Brazilian MMQ in a larger sample.

RESUMO Medidas de metamemória fornecem informações acerca da memória subjetiva e são relevantes para se compreender a habilidade de memória no envelhecimento. Todavia, há uma falta de instrumentos de metamemória disponíveis no Brasil. Objetivo: O presente trabalho teve como objetivo examinar as propriedades psicométricas da versão brasileira do Questionário Multifatorial de Memória (MMQ), que avalia diferentes aspectos da memória subjetiva, como Sentimentos, Habilidade e Estratégias usadas na vida diária. Métodos: O MMQ foi traduzido para o Português e administrado em 30 idosos brasileiros. Os participantes realizaram testes cognitivos, escalas de humor e questionários de metamemória. Resultados: Análises revelaram boa consistência interna (coeficiente a de Cronbach's variou de 0.75 a 0.89) e validade teste-reteste para cada dimensão do MMQ (correlações positivas entre as duas aplicações variou de 0.75 a 0.8). Validade convergente do MMQ foi identificada através de correlações positivas (0.47 a 0.68) com as dimensões do Metamemory In Adulthood Questionnaire (MIA) (i.e., Habilidade, Controle, Autoeficácia e Estratégia). Validade discriminante revelou ausência de associação entre MMQ e performance cognitiva, sugerindo uma fraca correspondência entre metamemória e memória objetiva. Além disto, observou-se uma correlação negativa entre os escores da subscala MMQ-Habilidade e sintomas do humor (-0.63 para sintomas ansiosos, e -0.54 para sintomas depressivos); e o MMQ Brasileiro se mostrou comparável a traduções do MMQ em outros idiomas. Conclusão: O MMQ Brasileiro apresenta boas propriedades psicométricas e parece ser promissor para o uso clínico e de pesquisa. Estudos adicionais são necessários para investigar caracteristicas psicométricas do MMQ Brasileiro em uma amostra maior.

Metamemory and aging: Psychometric properties of the Brazilian version of the Multifactorial Memory Questionnaire for elderly.

Metamemory measures provide subjective memory information and are relevant to investigate memory ability in aging. However, there is a lack of metamemory instruments available in Brazil. OBJECTIVE: The aim of this study was to examine the psychometric properties of the Brazilian version of the Multifactorial Memory Questionnaire (MMQ), which evaluates different dimensions of subjective memory functioning, such as Feelings, Abilities and Strategies used in everyday life. METHODS: The MMQ was translated into Portuguese and administered to 30 Brazilian elderly subjects. The participants underwent cognitive tests, mood scales and metamemory instruments. RESULTS: Analyses revealed good internal consistency (Cronbach's a coefficient ranged from 0.75 to 0.89) and test-retest validity for each MMQ dimensions (positive correlations between two applications ranged from 0.75 to 0.8). Convergent validity evidence for the MMQ was confirmed by significant positive correlations (0.47 to 0.68) with dimensions of the Metamemory in Adulthood scale (MIA) (i.e., the Ability, Control, Self-efficacy and Strategy dimensions). Discriminant validity revealed no associations between the MMQ and cognitive performance, suggesting a weak metamemory-objective memory correspondence. Moreover, there was a negative correlation between MMQ-Ability subscale scores and mood symptoms (-0.63 for anxious symptoms, and -0.54 for depressive symptoms); and the Brazilian MMQ was comparable with MMQ translations to other languages. CONCLUSION: The Brazilian MMQ exhibits good psychometric properties and appears promising for clinical and research purposes. Additional studies are needed to further examine the psychometric properties of the Brazilian MMQ in a larger sample.

Medidas de metamemória fornecem informações acerca da memória subjetiva e são relevantes para se compreender a habilidade de memória no envelhecimento. Todavia, há uma falta de instrumentos de metamemória disponíveis no Brasil. OBJETIVO: O presente trabalho teve como objetivo examinar as propriedades psicométricas da versão brasileira do Questionário Multifatorial de Memória (MMQ), que avalia diferentes aspectos da memória subjetiva, como Sentimentos, Habilidade e Estratégias usadas na vida diária. MÉTODOS: O MMQ foi traduzido para o Português e administrado em 30 idosos brasileiros. Os participantes realizaram testes cognitivos, escalas de humor e questionários de metamemória. RESULTADOS: Análises revelaram boa consistência interna (coeficiente a de Cronbach's variou de 0.75 a 0.89) e validade teste-reteste para cada dimensão do MMQ (correlações positivas entre as duas aplicações variou de 0.75 a 0.8). Validade convergente do MMQ foi identificada através de correlações positivas (0.47 a 0.68) com as dimensões do Metamemory In Adulthood Questionnaire (MIA) (i.e., Habilidade, Controle, Autoeficácia e Estratégia). Validade discriminante revelou ausência de associação entre MMQ e performance cognitiva, sugerindo uma fraca correspondência entre metamemória e memória objetiva. Além disto, observou-se uma correlação negativa entre os escores da subscala MMQ-Habilidade e sintomas do humor (-0.63 para sintomas ansiosos, e -0.54 para sintomas depressivos); e o MMQ Brasileiro se mostrou comparável a traduções do MMQ em outros idiomas. CONCLUSÃO: O MMQ Brasileiro apresenta boas propriedades psicométricas e parece ser promissor para o uso clínico e de pesquisa. Estudos adicionais são necessários para investigar caracteristicas psicométricas do MMQ Brasileiro em uma amostra maior.

Direct and indirect assessments of activities of daily living in behavioral variant frontotemporal dementia and Alzheimer disease.

BACKGROUND: There is limited information about the functional profile of behavioral variant frontotemporal dementia (bvFTD). OBJECTIVE: To compare direct and indirect assessments of activities of daily living (ADLs) in bvFTD and Alzheimer disease (AD) and their relationship with cognitive performance. METHODS: In all, 20 patients with bvFTD, 30 patients with AD, and 34 normal controls (NCs), matched for age, education, and severity of dementia, completed the Direct Assessment of Functional Performance (DAFS-BR) and usual cognitive measures. The Disability Assessment for Dementia (DAD) was completed by caregivers. RESULTS: In DAFS-BR, patients with bvFTD and AD had similar performance but lower than NCs. In DAD, there were no significant differences for effective performance, but patients with bvFTD had lower scores for initiation and planning/organization. Patients with bvFTD were less impaired than AD in cognition. CONCLUSION: Functional changes in bvFTD seem to be better documented by indirect measures.

Brazilian research on cognitive impairment and dementia from 1999 to 2013 / Pesquisa científica em comprometimento cognitivo e demência no Brasil de 1999 a 2013

The phenomenon of demographic transition in recent decades has increased the number of elderly people in Brazil, promoting an escalation in chronic-degenerative conditions, particularly dementia and cognitive related disorders. Objective: The aim of this study was to assess the evolution of the Brazilian scientific publications on dementia and related conditions from 1999 to 2013. Methods: Articles published during the analysis period were searched on three electronic databases: Scopus, Medline (via PubMed) and Lilacs (via BVS). The keywords used were Alzheimers disease, dementia and mild cognitive impairment, with Brazil as the country of affiliation. Results: A total of 1,657 articles met the conditions for inclusion in the study. The output of Brazilian researchers in the area of cognitive disorders increased 11.38-fold in the fifteen-year period of analysis and 4.98-fold from 2003 to 2013. More than half of the articles (53%) were published in international journals. The majority of institutions involved in publications were public universities while 19% were collaborative studies involving Brazilian and international institutions. Conclusion: Despite marked growth, the number of Brazilian scientific publications in the area of cognitive impairment and dementia is still low. More effort is required to improve the output of Brazilian researchers and institutions. Possible strategies to accomplish this increase could be to encourage residents to participate in publications of scientific papers during their residence program and to increase the collaborations between different institutions within Brazil and with the international scientific community.

O fenômeno da transição demográfica nas últimas décadas aumentou o número de indivíduos idosos no Brasil, promovendo um avanço de condições crônico-degenerativas, particularmente demência e outros distúrbios cognitivos relacionados. Objetivo: A intenção deste estudo foi avaliar a evolução da produção científica brasileira em demência e condições relacionadas de 1999 a 2013. Métodos: Pesquisamos artigos publicados durante esse período em três bancos de dados eletrônicos: Scopus, Medline (via PubMed) e Lilacs (via BVS). As palavras-chave utilizadas foram doença de Alzheimer, demência e comprometimento cognitivo leve, com o Brasil como país de afiliação. Resultados: Um total de 1.657 artigos cumpriram as condições para inclusão no estudo. A produção de pesquisadores brasileiros na área de distúrbios cognitivos aumentou 11,38 vezes no período de análise e 4,98 vezes de 2003 a 2013. Mais da metade dos artigos (53%) foi publicada em periódicos internacionais. A maioria das instituições envolvidas em publicações eram universidades públicas e 19% eram estudos colaborativos envolvendo instituições brasileiras e internacionais. Conclusão: Apesar do crescimento expressivo, o número de publicações cientificas brasileiras na área de comprometimento cognitivo e demência é ainda baixo. Mais esforços são necessários para melhorar a produção de pesquisadores e instituições brasileiras. Possíveis estratégias para cumprir essa tarefa poderiam ser encorajar residentes a participar de publicações de artigos científicos durante seu programa de residência e aumentar as colaborações entre diferentes instituições brasileiras e com a comunidade científica internacional.

Cognitive screening for dementia in primary care: a systematic review.

BACKGROUND: Identifying dementia in primary care could minimize the impact of a late intervention; however, it shows high rates of misdiagnosis. One of the reasons seems to be the lack of knowledge of adequate cognitive screening instruments. This is a systematic review of the available instruments for the primary care context. METHOD: For this systematic review, articles were collected according to the following combined key terms: "cognitive screening" and "dementia" and "primary care" and "review". Studies should be reviews focusing on cognitive screening instruments best used in primary care setting. RESULTS: Thirteen reviews were selected. In total, it was considered 34 cognitive screening instruments. Half of the instruments can be applied in an adequate time-limit for primary care context. Memory is the most commonly assessed cognitive function (91%). Almost half of the tests are mentioned to have influence of education or cultural factors (44%). CONCLUSION: Tests such as 6CIT, AMT, GPCOG, Mini-Cog, MIS, MoCA, and STMS seem to be good alternatives to the use of the Mini-Mental State Examination when considering factors such as application time, sensitivity, specificity, and number of studies. However, there is a wide range of tests with different characteristics, therefore it is recommended that the professional gets some expertise in a few number of instruments in order to be able to choose which to use, or use in combination, depending on the setting and the profile of the patient.

Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study).

UNLABELLED: The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. METHOD: Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. RESULTS: Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. CONCLUSION: GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658.

Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study) / Efeitos da galantamina e da galantamina combinada à nimodipina sobre a velocidade de processamento cognitivo e qualidade de vida na demência mista: ensaio clínico exploratório, randomizado e controlado com placebo (estudo REMIX)

The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. Method : Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. Results : Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. Conclusion : GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658 .

Os efeitos da galantamina (GAL) sobre qualidade de vida (QdV) e velocidade de processamento cognitivo, bem como da combinação com nimodipina (NIM) no tratamento da doença de Alzheimer (DA) com doença cerebrovascular (demência mista) ainda não foram investigados. Método : Estudo multicêntrico brasileiro, duplo-cego, controlado com placebo, avaliando os efeitos de GAL/NIM x GAL/placebo (PLA) na demência mista leve a moderada. Pacientes receberam tratamento com GAL/NIM ou GAL/PLA por 24 semanas. Medidas de eficácia primária foram as variações no desempenho em bateria de testes neuropsicológicos computadorizados e na escala QdV-DA ao final do estudo. Resultados : Vinte um pacientes receberam pelo menos uma dose da droga (9 GAL/NIM e 12 GAL/PLA). Os grupos foram emparelhados por idade, sexo, escolaridade, escores cognitivos e de QdV na linha de base. Não foram observadas diferenças significativas entre os dois grupos nas medidas de eficácia primária e secundária. Na avaliação de todos os pacientes que receberam GAL, houve melhora significativa (p<0,05) em QdV-DA e desempenho cognitivo. Os eventos adversos foram predominantemente leves a moderados. Conclusão : O tratamento com GAL proporcionou melhora da QdV na demência mista, além dos benefícios cognitivos previamente conhecidos. A combinação GAL/NIM não foi vantajosa. O reduzido tamanho amostral impede conclusões definitivas. .

Brazilian research on cognitive impairment and dementia from 1999 to 2013.

The phenomenon of demographic transition in recent decades has increased the number of elderly people in Brazil, promoting an escalation in chronic-degenerative conditions, particularly dementia and cognitive related disorders. OBJECTIVE: The aim of this study was to assess the evolution of the Brazilian scientific publications on dementia and related conditions from 1999 to 2013. METHODS: Articles published during the analysis period were searched on three electronic databases: Scopus, Medline (via PubMed) and Lilacs (via BVS). The keywords used were Alzheimer's disease, dementia and mild cognitive impairment, with Brazil as the country of affiliation. RESULTS: A total of 1,657 articles met the conditions for inclusion in the study. The output of Brazilian researchers in the area of cognitive disorders increased 11.38-fold in the fifteen-year period of analysis and 4.98-fold from 2003 to 2013. More than half of the articles (53%) were published in international journals. The majority of institutions involved in publications were public universities while 19% were collaborative studies involving Brazilian and international institutions. CONCLUSION: Despite marked growth, the number of Brazilian scientific publications in the area of cognitive impairment and dementia is still low. More effort is required to improve the output of Brazilian researchers and institutions. Possible strategies to accomplish this increase could be to encourage residents to participate in publications of scientific papers during their residence program and to increase the collaborations between different institutions within Brazil and with the international scientific community.

O fenômeno da transição demográfica nas últimas décadas aumentou o número de indivíduos idosos no Brasil, promovendo um avanço de condições crônico-degenerativas, particularmente demência e outros distúrbios cognitivos relacionados. OBJETIVO: A intenção deste estudo foi avaliar a evolução da produção científica brasileira em demência e condições relacionadas de 1999 a 2013. MÉTODOS: Pesquisamos artigos publicados durante esse período em três bancos de dados eletrônicos: Scopus, Medline (via PubMed) e Lilacs (via BVS). As palavras-chave utilizadas foram doença de Alzheimer, demência e comprometimento cognitivo leve, com o Brasil como país de afiliação. RESULTADOS: Um total de 1.657 artigos cumpriram as condições para inclusão no estudo. A produção de pesquisadores brasileiros na área de distúrbios cognitivos aumentou 11,38 vezes no período de análise e 4,98 vezes de 2003 a 2013. Mais da metade dos artigos (53%) foi publicada em periódicos internacionais. A maioria das instituições envolvidas em publicações eram universidades públicas e 19% eram estudos colaborativos envolvendo instituições brasileiras e internacionais. CONCLUSÃO: Apesar do crescimento expressivo, o número de publicações cientificas brasileiras na área de comprometimento cognitivo e demência é ainda baixo. Mais esforços são necessários para melhorar a produção de pesquisadores e instituições brasileiras. Possíveis estratégias para cumprir essa tarefa poderiam ser encorajar residentes a participar de publicações de artigos científicos durante seu programa de residência e aumentar as colaborações entre diferentes instituições brasileiras e com a comunidade científica internacional.

Translation, cross-cultural adaptation and applicability of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS) / Tradução, adaptação transcultural e aplicabilidade da Escala de Estadiamento e Progressão da Degeneração Lobar Frontotemporal

ABSTRACT Background: Staging scales for dementia have been devised for grading Alzheimer's disease (AD) but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD). Objective: To translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS) to Brazilian Portuguese. Methods: The cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators), discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0). The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), Executive Interview (EXIT-25), Neuropsychiatric Inventory (NPI), Frontotemporal Dementia Rating Scale (FTD-FRS) and Clinical Dementia Rating scale (CDR). Results: The Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate). It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0) in fact had moderate or severe levels of disability according to the FTD-FRS. Conclusion: The Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression.

RESUMO Introdução: As escalas de estadiamento das demências, como a Clinical Dementia Rating (CDR), foram elaboradas para graduar a doença de Alzheimer (DA) e não incluem os sintomas específicos da degeneração lobar frontotemporal (DLFT). Objetivo: Realizar a tradução e adaptação cultural da Frontotemporal Dementia Rating Scale (FTD-FRS) para o contexto brasileiro e apresentar dados preliminares da sua aplicabilidade. Métodos: O processo de adaptação transcultural consistiu em: tradução, retrotradução (realizadas por tradutores independentes), discussão com especialistas sobre a versão em português e equivalência com a versão original, desenvolvimento da versão final com pequenos ajustes. Foi feita uma aplicação piloto em 12 pacientes com diagnóstico de demência frontotemporal variante comportamental (DFTvc) e 11 com DA, pareados quanto à gravidade da demência (CDR=1). O protocolo de avaliação incluiu a Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini Exame do Estado Mental (MEEM), Executive Interview (EXIT-25), Inventário Neuropsiquiátrico (INP) e a Escala de Avaliação Clínica da Demência (CDR). Resultados: A FTD-FRS na versão brasileira pareceu apropriada. Resultados preliminares revelaram maiores níveis de incapacidade na DFTvc do que em pacientes com DA (DFTvc: 25% leve, 50% moderado, 25% grave; AD: 36.36% leve, 63.64% moderado). A CDR parece subestimar a gravidade da demência na DFTvc, uma vez que uma relevante proporção dos pacientes classificados com leves (CDR=1) de fato apresentaram nível moderado ou grave de comprometimento na FTD-FRS. Conclusão: A versão brasileira da FTD-FRS pode se mostrar adequada para auxiliar no estadiamento e determinar a progressão da DLFT.

Neurobiology of neuropsychiatric symptoms in Alzheimer?s disease / Neurobiologia dos Sintomas Neuropsiquiátricos na Doença de Alzheimer: Uma revisão crítica com foco na neuroimagem

The objective of this critical review of the literature was to reveal the neural circuits involved in the occurrence of neuropsychiatric symptoms (NPS) in Alzheimer?s disease (AD) patients through the association of these symptoms with neuroimaging findings. The search for articles was performed on PUBMED from January 2000 to May 2013, using thekey words: Dementia AND BPSD; Dementia AND Neuropsychiatric Symptoms; and Dementia AND Psychosis, Delusions, Hallucinations, Agitation, Depression, Anxiety, Apathy, Euphoria, Disinhibition, Irritability, Aberrant Motor Behavior, Sleep or Eating Disorders. Forty-six articles were reviewed and important contributions, especially regarding the psychopathological concepts discussed, were also considered even if not included in this time period. The available evidence suggests thethree most relevant neurobiological models for neuropsychiatric symptoms in Alzheimer?s disease are the frontal-subcortical circuits, the cortico-cortical networks, and the monoaminergic system. We discussed the association of the individual symptoms or syndromes with these models.

O objetivo dessa revisão crítica da literatura é investigar os circuitos neurais envolvidos na ocorrência dos sintomas neuropsiquiátricos nos pacientes com doença de Alzheimer através da associação destes sintomas com achados de neuroimagem. A procura dos artigos foi feita no PUBMED de Janeiro de 2000 a Maio de 2013, usando as palavras chave:Demência E BPSD; Demência E Sintomas Neuropsiquiátricos; e Demência E Psicose, Delírios, Alucinações, Agitação, Depressão, Ansiedade, Apatia, Euforia, Desinibição, Irritabilidade, Comportamento Motor Aberrante, Distúrbios do Sono ou Apetite. Quarenta e seis artigos foram revisados e contribuições importantes, especialmente considerando os conceitospsicopatológicos discutidos, foram também discutidos, mesmo se não incluídos neste período de tempo. As evidências disponíveis sugerem que os três modelos neurobiológicos mais relevantes para os sintomas neuropsiquiátricos na doença de Alzheimer são os circuitos frontal-subcorticais, as redes córtico-corticais, e o sistema monoaminérgico. Nós discutimos a associação dos sintomas individuais ou síndromes com esses modelos.

Correlation between neuropsychiatric symptoms and caregiver burden in a population-based sample from São Paulo, Brazil: a preliminary report / Correlação entre sintomas neuropsiquiátricos e sobrecarga do cuidador em uma amostra comunitária de São Paulo, Brasil: um relato preliminar

Neuropsychiatric symptoms and caregiver burden are highly prevalent in older adults with Alzheimer's disease (AD).OBJECTIVE: To evaluate the correlation between neuropsychiatric symptoms and caregiver burden in a community-based sample from São Paulo, Brazil. METHODS: A total of 1,563 randomly-selected subjects were assessed by the Mini-Mental State Examination, Fuld Object Memory Evaluation, Informant Questionnaire on Cognitive Decline in the Elderly and Bayer - Activities of Daily Living Scale. Subjects considered screen-positives were submitted to a dementia workup and diagnosis was determined according to ICD-10 criteria. The neuropsychiatric Inventory was applied to caregivers to evaluate neuropsychiatric symptoms and the Zarit Burden Interview was also applied to assess caregivers' burden. RESULTS: Sixty-one AD patients, 25 Cognitively Impaired Non Demented (CIND) and 79 healthy elderly subjects were evaluated. Zarit mean scores for controls, CIND and AD were 2.32, 3.92 and 20.11, respectively. There was strong positive correlation between total NPI and Zarit scores.

Sintomas neuropsiquiátricos e sobrecarga do cuidador apresentam alta prevalência em idosos com doença de Alzheimer (DA). OBJETIVO: Avaliar a correlação entre sintomas neuropsiquiátricos e sobrecarga do cuidador em uma amostra comunitária de São Paulo, Brasil. MÉTODOS: Um total de 1.563 indivíduos selecionados aleatóriamente foram avaliados através do Mini-Exame do Estado Mental, "Fuld Object Memory Evaluation", "Informant Questionnaire on Cognitive Decline in the Elderly" e da Escala Bayer - Atividades de Vida Diária. Indivíduos considerados suspeitos foram submetidos a uma investigação para demência, sendo o diagnóstico feito com os critérios da CID-10. Inventário Neuropsiquiátrico foi aplicado nos cuidadores para avaliar sintomas neuropsiquiátricos e a Escala Zarit de Sobrecarga no Cuidador para avaliar sobrecarga nos cuidadores. RESULTADOS: Sessenta e um pacientes com DA, 25 sujeitos com Comprometimento Cognitivo não Demência (CIND) e 79 idosos saudáveis foram avaliados. A média dos escores da Zarit para controles, CIND e DA foi, respectivamente, 2,32, 3,92 e 20,11 pontos. Houve correlação positiva boa entre os escores da NPI e da Zarit. CONCLUSÃO: Sintomas neuropsiquiátricos mostraram uma associação significativa com escores mais elevados de estresse do cuidador.

Depressive symptoms and cognitive deficits in a cancer patient submitted to chemotherapy with 5-Fluoracil: a case report / Sintomas depressivos e déficits cognitivos em paciente com câncer submetido a quimioterapia com 5-fluoracil: relato de caso

Cognitive deficits in cancer patients can be related to depression, anxiety, and the side effects of treatments such as fatigue. In this case report, we described an elderly patient with rectal adenocarcinoma, which presented depressive symptoms and memory complaints after treatment with 5-Fluoracil and Leucovorin. Depressive symptoms improved after two months but cognitive and functional impairment worsened suggesting the diagnosis of mild dementia. Structural and functional brain changes were seen on neuroimaging exams. Rivastigmine was introduced up to 12 mg/day, and after a one-year follow up the patient remained stable. Cognitive deficits can be a consequence of cancer therapies and a protocol to investigate deficits cognitive could be useful to the diferential diagnosis and management of elderly cancer patients submitted to chemotherapy.

Déficits cognitivos em pacientes com câncer podem estar relacionados à depressão, ansiedade e aos efeitos colaterais dos tratamentos, como fadiga. Neste relato de caso, descrevemos um paciente idoso com adenocarcinoma do reto, que apresentou sintomas depressivos e queixas de memória, após o tratamento com 5-Fluoracil e Leucovorin. Os sintomas depressivos melhoraram após dois meses, mas o comprometimento cognitivo e functional pioraram, sugerindo o diagnóstico de demência leve. Mudanças cerebrais estruturais e funcionais foram vistos em exames de neuroimagem. Rivastigmina foi introduzida até 12 mg/dia, e após um ano de seguimento o paciente permanecia estável. Déficits cognitivos podem ser consequência das terapias anti-neoplásicas e um protocolo para investigar déficits cognitivos pode ser útil para o diagnóstico diferencial e manejo de pacientes idosos com câncer submetidos à quimioterapia.