Maria Aparecida Bicalho

Propriedades psicométricas de um protocolo neuropsicológico breve para uso em populações geriátricas

CONTEXTO: O aumento na expectativa de vida e na proporcao de idosos na populacao tem acarretado elevacao nas taxas de prevalencia de demencias. O diagnostico correto da demencia e muito importante para o tratamento clinico e para um melhor prognostico. Por isso, e necessario adaptar e desenvolver instrumentos para o diagnostico diferencial entre os processos de envelhecimento normal e patologico. OBJETIVO: Avaliar as propriedades psicrometricas e a estrutura fatorial de um protocolo neuropsicologico usado para avaliacao geriatrica. METODO: Pacientes (n = 69) com queixas cognitivas heterogeneas foram avaliados no Nucleo de Geriatria e Gerontologia do Hospital das Clinicas da Universidade Federal de Minas Gerais, a partir de um protocolo composto pelo Miniexame do Estado Mental, Desenho do Relogio, Cubos de Corsi, Fluencia Verbal, Span de Digitos e Token Test. A analise estatistica incluiu analise fatorial dos resultados dos testes, correlacao de Pearson entre o fator obtido e a idade, escolaridade, anos de educacao formal e a Classificacao Clinica das Demencias (CDR) e a area sob a curva ROC. RESULTADOS: A analise fatorial dos escores do teste mostrou um fator geral representativo que teve associacao moderada e significativa com o CDR (r = -0,672; p < 0,001) e anos de educacao formal (r = 0,455; p < 0,001). Esse fator teve fraca, mas significativa, correlacao com a idade (r = -0,282; p < 0,05). CONCLUSAO: Esses resultados apontam para uma boa validade de construto e de criterio do protocolo na avaliacao do declinio cognitivo de idosos. Estudos futuros sobre aplicabilidade e normas populacionais sao necessarios para aprimorar o uso clinico desse protocolo de avaliacao.

Fidedignidade e validade de construto do Teste de Aprendizagem Auditivo-Verbal de Rey em idosos brasileiros

Background: The Rey Auditory-Verbal Learning Test (RAVLT) is widely used for the assessment of episodic memory. However, there are few studies in Brazil assessing its psychometric properties. Objectives: To search for evidence of reliability and construct validity of the RAVLT, and to assess the influence of age, schooling, gender, and depressive symptoms on test performance. Methods: One hundred twenty-six healthy older adults (aged 60 and over) performed the RAVLT, Mini-Mental State Exam (MMSE), Clock Drawing Test (CDT) and the Geriatric Depression Scale. Reliability was assessed by analysis of internal consistency, and construct validity by factor analysis and correlations with the MMSE and CDT. The influence of age, schooling and depressive symptoms was estimated by conducting linear regression analysis, and the role of gender by comparing the performance of males and females. Results: The RAVLT showed a high internal consistency, weak correlations with the MMSE and CDT, and a bifactorial structure, which is related to the processes of learning and episodic memory retrieval. Only age and gender affected test performance. Discussion: Our results provide evidence of reliability and construct validity in the tested RAVLT version, attesting its potential for clinical and research purposes for the Brazilian elderly population.

The Tower of London Test: Different Scoring Criteria for Diagnosing Alzheimer's Disease and Mild Cognitive Impairment

The Tower of London (TOL) is used for evaluating planning skills, which is a component of the executive functions. Different versions and scoring criteria were developed for this task, and some of them present with different psychometrical properties. This study aimed to evaluate two specific scoring methods of the TOL in diagnosing Mild Cognitive Impairment and probable Alzheimers disease. The TOL total scores from 60 patients of each diagnosis were compared with the performance of 60 healthy-aged controls using receiver operating characteristics analysis and multinomial logistic regression. Krikorian method better diagnosed Alzheimers disease, while Portellass was better at discriminating healthy controls from Mild Cognitive Impairment, but were not efficient at comparing this last group with Alzheimers patients. Regression analysis indicates that in addition to screening tests, TOL improves the classification of the three groups. The results suggest the two scoring methods used for this task may be useful for different diagnostic purposes.

Disease-specific expression of the serotonin-receptor 5-HT2C in natural killer cells in Alzheimer's dementia

Alzheimers 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.

Specific cognitive functions and depressive symptoms as predictors of activities of daily living in older adults with heterogeneous cognitive backgrounds

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.

Development, validity, and reliability of the General Activities of Daily Living Scale: a multidimensional measure of activities of daily living for older people

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 Alzheimers 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.

Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in late-onset depression patients.

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.

Impairment of fine motor dexterity in mild cognitive impairment and Alzheimer’s disease dementia: association with activities of daily living

Objective: Cognitive impairment is a hallmark of mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD). Although the cognitive profile of these patients and its association with activities of daily living (ADLs) is well documented, few studies have assessed deficits in fine motor dexterity and their association with ADL performance. The objective of this research paper is to evaluate fine motor dexterity performance among MCI and AD patients and to investigate its association with different aspects of ADLs. Methods: We assessed normal aging controls, patients with multiple- and single-domain amnestic MCI (aMCI), and patients with mild AD. Fine motor dexterity was measured with the Nine-Hole Peg Test and cognitive functioning by the Mattis Dementia Rating Scale. We analyzed the data using general linear models. Results: Patients with AD or multiple-domain aMCI had slower motor responses when compared to controls. AD patients were slower than those with single-domain aMCI. We found associations between cognition and instrumental ADLs, and between fine motor dexterity and self-care ADLs. Conclusion: We observed progressive slowing of fine motor dexterity along the normal aging-MCI-AD spectrum, which was associated with autonomy in self-care ADLs.

Spectrum of somatic EGFR, KRAS, BRAF, PTEN mutations and TTF-1 expression in Brazilian lung cancer patients.

Lung cancer is the leading global cause of cancer-related mortality. Inter-individual variability in treatment response and prognosis has been associated with genetic polymorphisms in specific genes: EGFR, KRAS, BRAF, PTEN and TTF-1. Somatic mutations in EGFR and KRAS genes are reported at rates of 15-40% in non-small cell lung cancer (NSCLC) in ethnically diverse populations. BRAF and PTEN are commonly mutated genes in various cancer types, including NSCLC, with PTEN mutations exerting an effect on the therapeutic response of EGFR/AKT/PI3K pathway inhibitors. TTF-1 is expressed in approximately 80% of lung adenocarcinomas and its positivity correlates with higher prevalence of EGFR mutation in this cancer type. To determine molecular markers for lung cancer in Brazilian patients, the rate of the predominant EGFR, KRAS, BRAF and PTEN mutations, as well as TTF-1 expression, was assessed in 88 Brazilian NSCLC patients. EGFR exon 19 deletions (del746-750) were detected in 3/88 (3·4%) patients. Activating KRAS mutations in codons 12 and 61 were noted in five (5·7%) and two (2·3%) patients, respectively. None of the common somatic mutations were detected in either the BRAF or PTEN genes. TTF-1 was overexpressed in 40·7% of squamous-cell carcinoma (SCC). Our findings add to a growing body of data that highlights the genetic heterogeneity of the abnormal EGFR pathway in lung cancer among ethnically diverse populations.

A Reanalysis of Cognitive-Functional Performance in Older Adults: Investigating the Interaction Between Normal Aging, Mild Cognitive Impairment, Mild Alzheimer's Disease Dementia, and Depression

Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimers disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N = 274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum.