Functional Disability in Alzheimer Disease A Validation Study of the Brazilian Version of the Disability Assessment for Dementia (DAD-Br)

Background: The assessment of activities of daily living (ADL) is important both for the diagnosis and staging of dementia. The objective of this study was to verify the applicability and validity of the Brazilian version of the Disability Assessment for Dementia (DAD-Br). Methods: The DAD was applied to caregivers of 89 patients with probable Alzheimer disease (AD) and to 40 elderly individuals without cognitive impairment (controls). We assessed the construct validity of the scale and its diagnostic accuracy (sensitivity, specificity, and predictive value). In addition, intergroup and intragroup analyses were conducted to characterize patient performance on basic and instrumental ADL and to determine underlying deficits (initiation, planning, or effective execution). Results: AD patients and controls had mean ages of 76.4 +/- 6.9 years and 74.5 +/- 7.3 years (P = 0.08), respectively. Mean Mini-Mental State Examination scores were 17.4 +/- 5.0 and 26.1 +/- 5.1 (P < 0.001) and scores on the DAD were 68.4 +/- 19.0 and 99.8 +/- 0.9 (P < 0.001), for patients and controls, respectively. The DAD scale showed good internal consistency (Cronbach alpha = 0.77) and correlation with the Mini-Mental State Examination (r = 0.44; P < 0.001). The AD group did better on basic ADL than on instrumental ADL (P < 0.001). As expected, controls did not exhibit significant deficits on the items evaluated. Conclusion: The Brazilian version of the DAD is an adequate and reliable tool for assessing functional ability in AD patients.

Synaptic vesicle transport and synaptic membrane transporter sites in excitatory amino acid nerve terminals in Alzheimer disease

The apparent L-[H-3]glutamate uptake rate (v') was measured in synaptic vesicles isolated from cerebral cortex synaptosomes prepared from autopsied Alzheimer and non-Alzheimer dementia cases, and age-matched controls. The initial synaptosome preparations exhibited similar densities of D-[H-3]aspartate membrane binding sites (B-MAX values) in the three groups. In control brain the temporal cortex D-[H-3]aspartate B-MAX was 132% of that in motor cortex, parallel with the L- [H-3]glutamate v' values (temporal = 139% of motor; NS). Unlike D- [H-3]aspartate B-MAX values, L- [H-3]glutamate v' values were markedly and selectively lower in Alzheimer brain preparations than in controls, particularly in temporal cortex. The difference could not be attributed to differential effects of autopsy interval or age at death. Non-Alzheimer dementia cases resembled controls. The selective loss of vesicular glutamate transport is consistent with a dysfunction in the recycling of transmitter glutamate.

Atividade física sistematizada e sintomas de depressão na demência de Alzheimer: uma revisão sistemática

OBJETIVO: Realizar uma revisão sistemática de artigos científicos que analisaram os efeitos da atividade física sistematizada nos sintomas de depressão de pacientes com demência de Alzheimer. MÉTODOS: Foi realizada uma busca nas seguintes bases de dados: Web of Science, PubMed, PsycINFO, MedLine e Biological Abstracts, utilizando-se as seguintes palavras-chave: "Alzheimer dementia" , "Alzheimer disease" , "Alzheimer, physical activity", "physical exercise", "motor intervention" , "physical therapy" , "exercise" , "aerobic" , "strength" , "fitness" , "depression" , "dysphoria" , "depressive symptoms" e "depressive episodes". Além da busca nas bases de dados, foi realizada também uma busca manual nas listas de referências dos artigos selecionados. RESULTADOS: Foram encontrados quatro estudos que preencheram todos os critérios de inclusão adotados para o presente trabalho. Dois estudos apresentaram reduções dos sintomas depressivos, e outros dois não encontraram redução desses sintomas. CONCLUSÃO: Com a realização desta revisão sistemática, observou-se que não há consenso em relação aos benefícios da atividade física aos sintomas depressivos em pacientes com demência de Alzheimer.

Consciência da doença na demência do tipo Alzheimer: uma revisão sistemática de estudos longitudinais

OBJETIVOS: Avaliar as definições, métodos de avaliação e hipóteses etiológicas utilizadas em estudos longitudinais sobre consciência da doença na demência do tipo Alzheimer. MÉTODO: Pesquisa, nas bases de dados Medline, ISI, Lilacs e SciELO, de estudos longitudinais sobre consciência da doença na demência do tipo Alzheimer entre 1999 e 2009. As palavras-chave utilizadas foram: "Alzheimer", "dementia", "anosognosia", "awareness of deficit", "awareness of disease", "insight" e "longitudinal study". Os artigos examinados foram classificados conforme as hipóteses etiológicas encontradas. RESULTADOS: Os nove artigos selecionados foram divididos em duas áreas: hipóteses etiológicas biológicas e hipóteses etiológicas psicossociais. Os termos "falta de consciência dos déficits", "consciência do déficit", "insight" e "negação do déficit de memória" são utilizados nos estudos como sinônimos do termo "anosognosia", mesmo sendo, conceitualmente, diferentes. O método de avaliação mais utilizado foi o uso de questionários de discrepância entre os relatos dos pacientes e cuidadores. CONCLUSÕES: Os estudos longitudinais apresentam hipóteses etiológicas heterogêneas, além da inexistência de um padrão conceitual e metodológico de avaliação. Essas dificuldades impossibilitam a obtenção de resultados homogêneos, o que gera a necessidade de aprofundamento dos estudos na área.

Approche psycholinguistique des relations entre le traitement sémantique des mots et la rétention à court terme chez l’individu sain et dans la démence de type Alzheimer

Depuis ces deux dernières décennies, des efforts considérables en psychologie cognitive et neuropsychologie ont été déployés pour mieux comprendre les dynamiques entre les différents systèmes cognitifs (fonctions exécutives, mémoire, langage, etc.). L’observation d’une co-existence entre des atteintes en rétention à court terme verbale (RCTv) et en langage dans plusieurs pathologies a conduit certains chercheurs à concevoir une alternative à la conceptualisation classique de la RCTv, telle que proposée par le modèle initial de la mémoire de travail de Baddeley (1986). Particulièrement, les travaux sur l’aphasie ont conduit à l’émergence d’une approche psycholinguistique de la RCTv, postulant que le traitement et le maintien des mots font appel à des processus communs. Cette approche, et particulièrement le modèle d’activation interactive (N. Martin & Gupta, 2004; N. Martin & Saffran, 1997), prédit que les capacités en RCTv sont notamment modulées par les caractéristiques linguistiques engagées durant l’épreuve, variant selon la nature des items verbaux et la modalité de rappel, ainsi que par les compétences linguistiques des individus. L’objectif de la présente thèse était de tester ces prédictions à partir d’une exploration des relations entre le traitement sémantique des mots et la RCTv chez l’adulte sain (article 1) et dans la démence de type Alzheimer (DTA) (article 2). Dans le premier article, deux expériences mettent en évidence l’influence des liens associatifs entre les mots sur les capacités à maintenir temporairement des informations verbales. Les participants ont tendance à faussement reconnaître des mots associés aux mots de la liste, reflet d’une activation du réseau sémantique durant la rétention temporaire. Cette contribution sémantique est accentuée en situation de suppression articulatoire, une condition qui empêche le participant de répéter les listes durant la tâche. Les résultats du second article indiquent que la modalité de réponse module différemment la performance en RCTv chez les participants âgés sans atteinte neurologique et ceux atteints de la DTA. Ces données en RCTv sont compatibles avec les atteintes spécifiques du traitement du mot, également trouvées chez le groupe avec DTA. Les implications théoriques et cliniques de ces résultats sont discutées. Les limites et perspectives futures sont également abordées.

Atividade física sistematizada e sintomas de depressão na demência de Alzheimer: uma revisão sistemática

OBJETIVO: Realizar uma revisão sistemática de artigos científicos que analisaram os efeitos da atividade física sistematizada nos sintomas de depressão de pacientes com demência de Alzheimer. MÉTODOS: Foi realizada uma busca nas seguintes bases de dados: Web of Science, PubMed, PsycINFO, MedLine e Biological Abstracts, utilizando-se as seguintes palavras-chave: Alzheimer dementia , Alzheimer disease , Alzheimer, physical activity, physical exercise, motor intervention , physical therapy , exercise , aerobic , strength , fitness , depression , dysphoria , depressive symptoms e depressive episodes. Além da busca nas bases de dados, foi realizada também uma busca manual nas listas de referências dos artigos selecionados. RESULTADOS: Foram encontrados quatro estudos que preencheram todos os critérios de inclusão adotados para o presente trabalho. Dois estudos apresentaram reduções dos sintomas depressivos, e outros dois não encontraram redução desses sintomas. CONCLUSÃO: Com a realização desta revisão sistemática, observou-se que não há consenso em relação aos benefícios da atividade física aos sintomas depressivos em pacientes com demência de Alzheimer.

Latência e amplitude do P300 auditivo na doença de Alzheimer: uma revisão sistemática

O P300 desempenha um papel fundamental como método de avaliação e monitoramento das demências, entre elas a doença de Alzheimer. OBJETIVO: Realizar uma busca por artigos que analisaram os valores de latência e amplitude de P300 na doença de Alzheimer. MÉTODOS: Foi realizada uma busca nas seguintes bases de dados: Web of Science, PubMed/Medline, Psyc Info, Biological Abstracts e Scielo. Utilizaram-se as seguintes palavras-chave: speed of information processing, speed of processing, information processing, aged, older, elderly, older people, alzheimer dementia, alzheimer disease, Alzheimer, além de referências cruzadas dos artigos selecionados. RESULTADOS: Foram encontrados oito estudos que preencheram os critérios de inclusão adotados para o presente trabalho. Estes estudos mostraram que existe um consenso em relação ao aumento da latência de P300 de idosos com doença de Alzheimer quando comparados com idosos sem a doença. Porém, verifica-se que, com relação à amplitude de P300, ainda não há um consenso, mas, isso pode estar relacionado às diferentes variáveis metodológicas adotadas nos estudos revisados. CONCLUSÃO: Há necessidade de se padronizar as variáveis envolvidas no método de avaliação do P300 para idosos com doença de Alzheimer, para que seja possível comparar os valores de latência e amplitude de P300 dessa população.

Multimodal exercise intervention improves frontal cognitive functions and gait in Alzheimer's disease: A controlled trial

Aim: The objective of the present study was to investigate the effect of a multimodal exercise intervention on frontal cognitive functions and kinematic gait parameters in patients with Alzheimer's disease. Methods: A sample of elderly patients with Alzheimer's disease (n=27) were assigned to a training group (n=14; aged 78.0±7.3years) and a control group (n=13; aged 77.1±7.4years). Multimodal exercise intervention includes motor activities and cognitive tasks simultaneously. The participants attended a 1-h session three times a week for 16weeks, and the control participants maintained their regular daily activities during the same period. The frontal cognitive functions were evaluated using the Frontal Assessment Battery, the Clock Drawing Test and the Symbol Search Subtest. The kinematic parameters of gait-cadence, stride length and stride speed were analyzed under two conditions: (i) free gait (single task); and (ii) gait with frontal cognitive task (walking and counting down from 20 - dual task). Results and discussion: The patients in the intervention group significantly increased the scores in frontal cognitive variables, Frontal Assessment Battery (P<0.001) and Symbol Search Subtest (P<0.001) after the 16-week period. The control group decreased the scores in the Clock Drawing Test (P=0.001) and increased the number of counting errors during the dual task (P=0.008) after the same period. Conclusion: The multimodal exercise intervention improved the frontal cognitive functions in patients with Alzheimer's disease. © 2012 Japan Geriatrics Society.

Efeitos de um programa de intervenção motora nos distúrbios neuropsiquiátricos e nas atividades funcionais de pacientes com demência de Alzheimer e em seus cuidadores

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Variability in obstacle clearance may (not) indicate cognitive disorders in alzheimer disease

The aim of this study was to investigate obstacle clearance and its variability in individuals with Alzheimer dementia (AD) as well as healthy elderly individuals while they approached and crossed an obstacle in their path. Fifteen people with AD and 15 age-matched/sex-matched healthy individuals (control group) participated in this study. Clinical assessment of both groups was performed by a neuropsychiatrist. Spatial-temporal parameters of 5 trials of unobstructed walking and 5 trials of obstacle crossing during walking (approach and crossing phases) were measured using a 3-dimensional optoelectronic system. The results indicated that individuals with AD showed higher variability in the approach phase for stride length and the horizontal distance from their trailing limb foot to the obstacle. However, their gait variability in the crossing phase was similar to the control group. In addition, the individuals with AD were found to walk slowly and with a short stride length in both conditions. In conclusion, individuals with AD had increased gait variability while approaching an obstacle during walking, indicating a deficit in planning to avoid obstacles that could be related to cognitive disorders. However, gait variability during the crossing phase may not be indicative of cognitive disorders in AD.

Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.

Cerebrospinal fluid biomarkers of central nervous system dysfunction in HIV-infected patients

Background :¦In addition to opportunistic infections of the central nervous system (CNS), which are due to immunosuppression related to HIV, the latter virus, itself, can cause neuropathological abnormalities which are located mainly in the basal ganglia and are characterized by microglial giant cells, reactive astrocytosis and perivascular monocytes. This HIV encephalopathy is characterized, clinically, by psycho-motor slowing, memory loss, difficulties in complex tasks requiring executive functions, as well as motor disorders .These cognitive deficits are grouped under the acronym of HIV-associated neurocognitive disorders (HAND). In fact, HANDs are subdivided in three groups in accordance with the severity of the cognitive impairment: Asymptomatic Neurocognitive Impairment (ANI), Mild/moderate Neurocognitive Disorders (MND) and HIV Associated Dementia (HAD).¦While the incidence of HAD has significantly decreased in the era of combined antiretrobiral therapy (cART), the prevalence of milder forms of HIV-associated neurocognitive disorders HAND seem to have increased. There are many potential reasons to explain this state of facts.¦An important question is to understand how soon the brain may be affected by HIV. Since performing a biopsy in these patients is not an issue, the study of the CSF represents the best available way to look at putative biomarkers of inflammation/neurodegeneration in the CNS. Here, we wanted to examined the putative usefulness of different biomarkers as early indicators of anti-retroviral failure at the level of the CNS. We chose to study the CSF levels of:¦Amyloid-β 1-42 (Aβ42), Tau total (tTau), phosphorylated Tau (pTau), Neopterin and S100-β.¦Indeed, these molecules are representative biomarkers of the major cells of the CNS, i.e. neurons,¦macrophages/microglia and astrocytes.¦To examine how sensitive were these CSF biomarkers to indicate CNS insults caused by HIV, we proposed to take advantage of the MOST (Monotherapy Switzerland/Thailand study) study, recently published in AIDS. Thus, we collaborated with Prof. Pietro Vernazza in St-Gall. In MOST study, monotherapy (MT) consisting in ritonavir-boosted lopinavir (LPV/r) was compared to continuous conventional antiretroviral therapy including several molecules, hereafter referred as CT¦Methods :We tested 61 cerebrospinal fluid (CSF) samples from 52 patients enrolled in MOST, including 34 CSF samples of CT and 27 of MT (mean duration on MT: 47+20 weeks) in patients who maintained full VL suppression in blood (<50cps/ml). Using enzyme-linked immunosorbent assay (ELISA), we determined the CSF concentration of S100-beta (astrocytosis), neopterin (microglia, inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-beta 1-42 (Abeta), the latter three markers indicating neuronal damages. The CSF samples of 37 HIV-negative patients with Alzheimer dementia (AD) served as controls. Results are expressed in pg/ml and reported as median ± interquartile range. Mann Whitney-U test was used to compare the results of a given biomarker between two groups and the Fisher test to compare frequencies.¦Results: We found a higher concentration of S100-beta (570±1132) and neopterin (2.5±2.9) in the CSF of MT versus CT (0±532, p=0.002 and 1.2±2.5, p=0.058, respectively). A cutoff of 940 pg/ml for S100-beta allowed to discriminate MT (11 above versus 16 below) from CT (1 vs 33, p=0.0003). At a lesser extent, a cutoff of 11 pg/ml for neopterin separated MT (4 above versus 23) from CT (0 vs 34, p=0.034) (Figure).¦In AD, tTau was higher (270±414) and Abeta lower (234±328) than in CT (150±153, p=0.0078, and 466±489, p=0.007, respectively). Such as for CT, Abeta was lower in AD than in MT (390±412, p=0.01). However, contrasting with CT, the levels of tTau were not different between AD and MT (199±177, p=0.11). S100b (173±214; p=0.0006) and neopterin (1.1±0.9; p=0.0014) were lower in AD than MT.¦Conclusions: Despite full VL-suppression in blood, HIV monotherapy is sufficient to trigger inflammation and, especially, astrocytosis. CSF markers of patients on CT have the same profile as reported for healthy subjects, suggesting that CT permits a good control of HIV in the brain. Finally, the levels of tTau, which are relatively similar between AD and MT patients, suggest that neurons are damaged during monotherapy.

Marked increase of the astrocytic marker S100B in the cerebrospinal fluid of HIV-infected patients on LPV/r-monotherapy.

OBJECTIVE: To determine changes of cerebrospinal fluid (CSF) biomarkers of patients on monotherapy with lopinavir/ritonavir. DESIGN: The Monotherapy Switzerland/Thailand study (MOST) trial compared monotherapy with ritonavir-boosted lopinavir with continued therapy. The trial was prematurely stopped due to virological failure in six patients on monotherapy. It, thus, offers a unique opportunity to assess brain markers in the early stage of HIV virological escape. METHODS: : Sixty-five CSF samples (34 on continued therapy and 31 on monotherapy) from 49 HIV-positive patients enrolled in MOST. Using enzyme-linked immunosorbent assay, we determined the CSF concentration of S100B (astrocytosis), neopterin (inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-β 1-42 (Aβ), the latter three indicating neuronal damage. Controls were CSF samples of 29 HIV-negative patients with Alzheimer dementia. RESULTS: In the CSF of monotherapy, concentrations of S100B and neopterin were significantly higher than in continued therapy (P = 0.006 and P = 0.013, respectively) and Alzheimer dementia patients (P < 0.0001 and P = 0.0005, respectively). In Alzheimer dementia, concentration of Aβ was lower than in monotherapy (P = 0.005) and continued therapy (P = 0.016) and concentrations of tTau were higher than in monotherapy (P = 0.019) and continued therapy (P = 0.001). There was no difference in pTau among the three groups. After removal of the 16 CSF with detectable viral load in the blood and/or CSF, only S100B remained significantly higher in monotherapy than in the two other groups. CONCLUSION: Despite full viral load-suppression in blood and CSF, antiretroviral monotherapy with lopinavir/ritonavir can raise CSF levels of S100B, suggesting astrocytic damage.

Eficacia de los inhibidores selectivos de recaptación de serotonina en síntomas no cognitivos del alzhéimer: revisión sistemática

Introducción: El Alzhéimer tiene una prevalencia de 1,6% en las personas mayores de 65 años. Se caracteriza por la pérdida de memoria y otras funciones cognoscitivas, pero más del 70% de los afectados presentan síntomas no cognitivos entre los que se encuentran alteraciones del afecto, comportamiento y psicosis. Estos síntomas están asociados a mayores tasas de institucionalización, morbilidad y mortalidad. Métodos: Revisión sistemática de la literatura de artículos que proporcionaron información sobre la eficacia de los inhibidores selectivos de recaptación de serotonina en síntomas no cognitivos del Alzhéimer. Resultados: La búsqueda inicial arrojó un total de 495 resultados, 64 artículos fueron preseleccionados y 7 se incluyeron en la revisión; éstos se clasificaron como nivel de evidencia Ib; citalopram mostró ser más eficaz que el placebo y similar a antipsicóticos para síntomas comportamentales y psicóticos asociados al Alzhéimer con un perfil de efectos adversos más tolerable; sertralina no mostró eficacia en depresión y sí una mayor incidencia de efectos adversos con respecto al placebo. Discusión: Se obtuvieron resultados favorables en síntomas comportamentales y psicóticos pero no en afectivos. Las diferencias metodológicas de los estudios le dan complejidad a la interpretación de los resultados. Conclusión: La evidencia sugiere que el tratamiento con citalopram es eficaz en síntomas comportamentales y psicóticos asociados al Alzhéimer; para el tratamiento de la depresión asociado a esta demencia aún no existe un antidepresivo que pueda considerarse de elección.

Atividade física e aspectos neuropsiquiátricos em pacientes com demência e em seus cuidadores

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)