Validade da versão em português da Clinical Dementia Rating

OBJETIVO: Analisar a validade da versão em português da Clinical Dementia Rating para classificar a função cognitiva de idosos. MÉTODOS: Utilizou-se o instrumento Mini-Mental State Examination para rastreamento de déficit cognitivo em coorte composta por 424 idosos. Foram selecionados todos que obtiveram escores <26 (108 idosos) e 48 idosos com escores >26. Os 156 idosos selecionados foram submetidos a uma avaliação clínica e testes neuropsicológicos para diagnóstico de casos de demência. Tanto os casos como os não-casos foram classificados segundo a versão em português da Clinical Dementia Rating em: normais, casos questionáveis e casos de demência leve, moderada ou grave. RESULTADOS: Entre os 156 avaliados, 122 eram não-casos, destes 62 (51%) foram classificados como normais (CDR=0) e questionáveis 60 (49%) (CDR=0,5). Entre os 34 casos de demência, 17 (50%) foram classificados como demência leve (CDR=1), 8 (23%) moderada (CDR=2) e 6 (18%) grave (CDR=3). Apenas três (9%) dos casos foram considerados questionáveis pelo Clinical Dementia Rating. Sua sensibilidade foi de 91,2% e a especificidade de 100%, com valor preditivo positivo de 100% e negativo de 97,6%. As pontuações no Mini-Mental State Examination declinaram significativamente conforme o grau de demência. CONCLUSÕES: O Clinical Dementia Rating mostrou ser instrumento válido para classificar o grau de demência entre idosos. Quase metade dos não-casos foram casos questionáveis pelo Clinical Dementia Rating e podem corresponder a casos de transtorno cognitivo leve, com maior risco de conversão em demência.

The Brazilian version of the Neuropsychiatric Inventory-Clinician rating scale (NPI-C): Reliability and validity in dementia

ABSTRACT Background: Patients with dementia may be unable to describe their symptoms, and caregivers frequently suffer emotional burden that can interfere with judgment of the patient's behavior. The Neuropsychiatric Inventory-Clinician rating scale (NPI-C) was therefore developed as a comprehensive and versatile instrument to assess and accurately measure neuropsychiatric symptoms (NPS) in dementia, thereby using information from caregiver and patient interviews, and any other relevant available data. The present study is a follow-up to the original, cross-national NPI-C validation, evaluating the reliability and concurrent validity of the NPI-C in quantifying psychopathological symptoms in dementia in a large Brazilian cohort. Methods: Two blinded raters evaluated 312 participants (156 patient-knowledgeable informant dyads) using the NPI-C for a total of 624 observations in five Brazilian centers. Inter-rater reliability was determined through intraclass correlation coefficients for the NPI-C domains and the traditional NPI. Convergent validity included correlations of specific domains of the NPI-C with the Brief Psychiatric Rating Scale (BPRS), the Cohen-Mansfield Agitation Index (CMAI), the Cornell Scale for Depression in Dementia (CSDD), and the Apathy Inventory (AI). Results: Inter-rater reliability was strong for all NPI-C domains. There were high correlations between NPI-C/delusions and BPRS, NPI-C/apathy-indifference with the AI, NPI-C/depression-dysphoria with the CSDD, NPI-C/agitation with the CMAI, and NPI-C/aggression with the CMAI. There was moderate correlation between the NPI-C/aberrant vocalizations and CMAI and the NPI-C/hallucinations with the BPRS. Conclusion: The NPI-C is a comprehensive tool that provides accurate measurement of NPS in dementia with high concurrent validity and inter-rater reliability in the Brazilian setting. In addition to universal assessment, the NPI-C can be completed by individual domains. © International Psychogeriatric Association 2013.

Incidence of dementia and cause of death in elderly Japanese emigrants to Brazil before World War II

In 1997 we examined the prevalence of dementia among the Japanese elderly immigrants living in the Sao Paulo metropolitan area (n = 166). Herein, we followed up on these subjects for causes of death and dementia incidence. We were able to contact 108 subjects: 54 were already dead. The most common cause of death was cardiac disease. For dementia, 31.6% of the dead subjects were found to have developed dementia before they died, and 20.8% of the living subjects were demented. As for the baseline the clinical dementia rating (CDR), 20.8% of CDR 0 and 50.0% of CDR 0.5 subjects developed dementia in the dead group; whereas in the living group, 23.9% of CDR 0 and 52.6% of CDR 0.5 developed dementia. As a whole, the incidence was 34.2% per 1000 person-years. Cardiac disease as the most common cause of death was probably due to the higher prevalence of diabetes mellitus. Compared with the previous study, the lower incidence of dementia from the CDR 0.5 group may have been due to a higher mortality rate. This is the first study on the incidence of dementia in elderly Japanese immigrants in Brazil. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old.

The relative contributions of Alzheimer disease (AD) and vascular lesion burden to the occurrence of cognitive decline are more difficult to define in the oldest-old than they are in younger cohorts. To address this issue, we examined 93 prospectively documented autopsy cases from 90 to 103 years with various degrees of AD lesions, lacunes, and microvascular pathology. Cognitive assessment was performed prospectively using the Clinical Dementia Rating scale. Neuropathologic evaluation included the Braak neurofibrillary tangle (NFT) and β-amyloid (Aβ) protein deposition staging and bilateral semiquantitative assessment of vascular lesions. Statistics included regression models and receiver operating characteristic analyses. Braak NFTs, Aβ deposition, and cortical microinfarcts (CMIs) predicted 30% of Clinical Dementia Rating variability and 49% of the presence of dementia. Braak NFT and CMI thresholds yielded 0.82 sensitivity, 0.91 specificity, and 0.84 correct classification rates for dementia. Using these threshold values, we could distinguish 3 groups of demented cases and propose criteria for neuropathologic definition of mixed dementia, pure vascular dementia, and AD in very old age. Braak NFT staging and severity of CMI allow for defining most of demented cases in the oldest-old. Most importantly, single cutoff scores for these variables that could be used in the future to formulate neuropathologic criteria for mixed dementia in this age group were identified.

Identification of dementia cases in the community: A Brazilian experience

OBJECTIVES: To describe the application in Brazil of a simple, low-cost procedure, developed in India by the 10/66 Dementia Research Group, for the identification of dementia cases in the community.DESIGN: Community-based dementia case-finding method.SETTING: Piraju, São Paulo, Brazil.PARTICIPANTS: Twenty-five community health workers were trained to identify dementia cases in 2,222 people aged 65 and older in Piraju, a Brazilian town with 27,871 inhabitants.MEAUREMENTS: After the training, the health workers prepared a list of possible cases that afterward an experienced psychiatrist clinically evaluated, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria and the Clinical Dementia Rating.RESULTS: of the 72 cases that were clinically assessed, 45 met the DSM-IV diagnostic criteria for dementia. Therefore, the positive predictive value of this case finding method was 62.5%; the estimated frequency of dementia was 2%. Most of the confirmed cases met clinical criteria for Alzheimer's disease and vascular dementia.CONCLUSION: This simple method was appropriate to identify cases of dementia in the general population and can possibly be extended to other developing countries with limited resources to be applied in health programs.

A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease

OBJETIVO: Analisar os efeitos de seis meses de intervenção de um programa de atividade física sobre os distúrbios neuropsiquiátricos e o desempenho nas atividades instrumentais da vida diária de idosos com Doença de Alzheimer (DA). MÉTODOS: Foram recrutados 20 pacientes nos estágios entre leve e moderado da DA. Segundo o escore clínico de demência (CDR), foram distribuídos em dois grupos: o grupo treinamento (GT), composto por dez mulheres que participaram de um program de exercícios físicos por um período de seis meses, e o grupo controle (GC), composto por dez outras participantes que não realizaram nenhum tipo de intervenção motora estruturada durante o mesmo período. Todas as participantes foram avaliadas por meio do Miniexame do Estado Mental, para obtenção da caracterização cognitiva; Inventário Neuropsiquiátrico, para identificação dos distúrbios neuropsiquiátricos mais prevalentes e Questionário de Atividades Instrumentais de Pfeffer, para verificação do grau de comprometimento funcional. RESULTADOS: Os participantes do GC mostraram uma deterioração tanto no desempenho das atividades instrumentais quanto na intensificação dos distúrbios neuropsiquiátricos, quando comparados os momentos pré e pós-intervenção. CONCLUSÃO: O GT demonstrou uma atenuação da intensificação dos distúrbios neuropsiquiátricos e do desempenho funcional em relação ao grupo sedentário.

Caregiver report versus clinician impression: disagreements in rating neuropsychiatric symptoms in Alzheimer's disease patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Semantic Dementia Versus Nonfluent Progressive Aphasia Neuropsychological Characterization and Differentiation

Background: Early progressive nonfluent aphasia (PNFA) may be difficult to differentiate from semantic dementia (SD) in a nonspecialist setting. There are descriptions of the clinical and neuropsychological profiles of patients with PNFA and SD but few systematic comparisons. Method: We compared the performance of groups with SD (n = 27) and PNFA (n = 16) with comparable ages, education, disease duration, and severity of dementia as measured by the Clinical Dementia Rating Scale on a comprehensive neuropsychological battery. Principal components analysis and intergroup comparisons were used. Results: A 5-factor solution accounted for 78.4% of the total variance with good separation of neuropsychological variables. As expected, both groups were anomic with preserved visuospatial function and mental speed. Patients with SD had lower scores on comprehension-based semantic tests and better performance on verbal working memory and phonological processing tasks. The opposite pattern was found in the PNFA group. Conclusions: Neuropsychological tests that examine verbal and nonverbal semantic associations, verbal working memory, and phonological processing are the most helpful for distinguishing between PNFA and SD.

Dementia severity of the care receiver predicts procoagulant response in Alzheimer caregivers

BACKGROUND: The procoagulant factor D-dimer has been shown to be associated with thrombus formation and degradation as seen with conditions such as myocardial infarction and unstable angina. Research has demonstrated that spousal dementia caregivers have elevated levels of D-dimer relative to their non-caregiving peers. OBJECTIVE: The objective of this study was to determine the relationship of basal level and laboratory stressor-induced concentration of D-dimer to severity of dementia in spousal care recipients. METHODS: Seventy-one elderly caregivers were compared with a comparison group of 37 non-caregivers (average age: 71 years). Clinical Dementia Rating (CDR), a global measure of dementia, was used to assess severity of spousal dementia. Plasma D-dimer was measured at baseline and in response to an acute speech stressor. RESULTS: Regression analysis revealed a significant positive association between severity of spousal dementia and caregiver D-dimer, both at baseline and in response to acute stress, while controlling for age. The model examined an exponential relationship, with D-dimer increasing progressively across the span of dementia stages. DISCUSSION: Dementia severity of the care recipient was associated with increasing hypercoagulability among elderly caregivers. Effect size estimates suggest that such D-dimer increases may have clinical implications, particularly among late-stage caregivers.

Effects of gender and dementia severity on Alzheimer's disease caregivers' sleep and biomarkers of coagulation and inflammation

BACKGROUND: Being a caregiver for a spouse with Alzheimer's disease is associated with increased risk for cardiovascular illness, particularly for males. This study examined the effects of caregiver gender and severity of the spouse's dementia on sleep, coagulation, and inflammation in the caregiver. METHODS: Eighty-one male and female spousal caregivers and 41 non-caregivers participated (mean age of all participants 70.2 years). Full-night polysomnography (PSG) was recorded in each participants home. Severity of the Alzheimer's disease patient's dementia was determined by the Clinical Dementia Rating (CDR) scale. The Role Overload scale was completed as an assessment of caregiving stress. Blood was drawn to assess circulating levels of D-dimer and Interleukin-6 (IL-6). RESULTS: Male caregivers who were caring for a spouse with moderate to severe dementia spent significantly more time awake after sleep onset than female caregivers caring for spouses with moderate to severe dementia (p=.011), who spent a similar amount of time awake after sleep onset to caregivers of low dementia spouses and to non-caregivers. Similarly, male caregivers caring for spouses with worse dementia had significantly higher circulating levels of D-dimer (p=.034) than females caring for spouses with worse dementia. In multiple regression analysis (adjusted R(2)=.270, p<.001), elevated D-dimer levels were predicted by a combination of the CDR rating of the patient (p=.047) as well as greater time awake after sleep onset (p=.046). DISCUSSION: The findings suggest that males caring for spouses with more severe dementia experience more disturbed sleep and have greater coagulation, the latter being associated with the disturbed sleep. These findings may provide insight into why male caregivers of spouses with Alzheimer's disease are at increased risk for illness, particularly cardiovascular disease.

Prevalence of mixed neuropathologies in autopsied older adults and associations with clinical disease progression

Thesis (Ph.D.)--University of Washington, 2016-06

Validity of the Katz Index to assess activities of daily living by informants in neuropathological studies

Abstract OBJECTIVE To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL) by informants, to assist neuropathological studies in the elderly. METHOD A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG) database. Sample was divided in two subsamples for the analysis (N=325, each) and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR). Factor analyses with calculations of internal consistency and invariance were performed. RESULTS Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.

Demyelination of superficial white matter in early Alzheimer's disease: a magnetization transfer imaging study.

Assuming selective vulnerability of short association U-fibers in early Alzheimer's disease (AD), we quantified demyelination of the surface white matter (dSWM) with magnetization transfer ratio (MTR) in 15 patients (Clinical Dementia Rating Scale [CDR] 0.5-1; Functional Assessment Staging [FAST]: 3-4) compared with 15 controls. MTRs were computed for 39 areas in each hemisphere. We found a bilateral MTR decrease in the temporal, cingulate, parietal, and prefrontal areas. With linear discriminant analysis, we successfully classified all the participants with 3 variates including the cuneus, parahippocampal, and superior temporal regions of the left hemisphere. The pattern of dSWM changed with the age of AD onset. In early onset patients, we found bilateral posterior demyelination spreading to the temporal areas in the left hemisphere. The late onset patients showed a distributed bilateral pattern with the temporal and cingulate areas strongly affected. A correlation with Mini Mental State Examination (MMSE), Lexis, and memory tests revealed the dSWM impact on cognition. A specific landscape of dSWM in early AD shows the potential of MTR imaging as an in vivo biomarker superior to currently used techniques.

Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

The loss of presynaptic markers is thought to represent a strong pathologic correlate of cognitive decline in Alzheimer's disease (AD). Spinophilin is a postsynaptic marker mainly located to the heads of dendritic spines. We assessed total numbers of spinophilin-immunoreactive puncta. in the CA I and CA3 fields of hippocampus and area 9 in 18 elderly individuals with various degrees of cognitive decline. The decrease in spinophilin-immunoreactivity was significantly related to both Braak neurofibrillary tangle (NFT) staging and clinical severity but not A beta deposition staging. The total number of spinophilin-immunoreactive puncta in CA I field and area 9 were significantly related to MMSE scores and predicted 23.5 and 61.9% of its variability. The relationship between total number of spinophilin-immunoreactive puncta in CA I field and MMSE scores did not persist when adjusting for Braak NFT staging. In contrast, the total number of spinophilin-immunoreactive puncta in area 9 was still significantly related to the cognitive outcome explaining an extra 9.6% of MMSE and 25.6% of the Clinical Dementia Rating scores variability. Our data suggest that neocortical dendritic spine loss is an independent parameter to consider in AD clinicopathologic correlations.

Interhemispheric distribution of Alzheimer disease and vascular pathology in brain aging

BACKGROUND AND PURPOSE: Most of the neuropathological studies in brain aging were based on the assumption of a symmetrical right-left hemisphere distribution of both Alzheimer disease and vascular pathology. To explore the impact of asymmetrical lesion formation on cognition, we performed a clinicopathological analysis of 153 cases with mixed pathology except macroinfarcts. METHODS: Cognitive status was assessed prospectively using the Clinical Dementia Rating scale; neuropathological evaluation included assessment of Braak neurofibrillary tangle and Ass deposition staging, microvascular pathology, and lacunes. The right-left hemisphere differences in neuropathological scores were evaluated using the Wilcoxon signed rank test. The relationship between the interhemispheric distribution of lesions and Clinical Dementia Rating scores was assessed using ordered logistic regression. RESULTS: Unlike Braak neurofibrillary tangle and Ass deposition staging, vascular scores were significantly higher in the left hemisphere for all Clinical Dementia Rating scores. A negative relationship was found between Braak neurofibrillary tangle, but not Ass staging, and vascular scores in cases with moderate to severe dementia. In both hemispheres, Braak neurofibrillary tangle staging was the main determinant of cognitive decline followed by vascular scores and Ass deposition staging. The concomitant predominance of Alzheimer disease and vascular pathology in the right hemisphere was associated with significantly higher Clinical Dementia Rating scores. CONCLUSIONS: Our data show that the cognitive impact of Alzheimer disease and vascular lesions in mixed cases may be assessed unilaterally without major information loss. However, interhemispheric differences and, in particular, increased vascular and Alzheimer disease burden in the right hemisphere may increase the risk for dementia in this group.