Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms.

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

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.

Working Memory and Cognitive Flexibility Mediates Visuoconstructional Abilities in Older Adults with Heterogeneous Cognitive Ability.

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

Predictive factors of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study.

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

Psychometric properties of the Brazilian version of Pfeffer's Functional Activities Questionnaire.

Pfeffer's Functional Activities Questionnaire (FAQ) is one of the most commonly employed tools in studies on pathological cognitive aging. Despite the different versions of the questionnaire translated for use in clinical practice, few studies have analyzed the psychometric properties of the Brazilian version of the FAQ (P-FAQ). Thus, the aim of the present study was to analyze the P-FAQ with regard to internal consistency, factorial structure and associations with demographic factors (age, sex, and schooling), depressive symptoms, cognitive measures and other measures of functionality. One hundred sixty-one older adults were divided into four groups (91 with dementia, 46 with mild cognitive impairment, 11 with psychiatric disorders and 13 healthy controls). All participants were evaluated by cognitive, behavioral and functional tests and scales. Their caregivers answered the P-FAQ. The questionnaire showed high internal consistency (α = 0.91). Factor analysis revealed a two-factor structure, which, accounted for 66% of the total variance. The P-FAQ was not correlated with demographic factors, was weakly correlated with depressive symptoms (ϱ = 0.271, p < 0.01, R (2) = 7%) and strongly correlated with cognitive measures (Matttis Dementia Rating Scale total score: ϱ = -0.574, p < 0.01, R (2) = 33%) as well as complex instrumental activities of daily living (ϱ = -0.845, p < 0.01, R (2) = 71%). Cognitive performance and depression status were independent predictors of P-FAQ scores in regression models. The present findings indicate that the P-FAQ has satisfactory reliability, internal consistency, construct validity and ecological validity. Therefore, this questionnaire can be used in clinical practice and research involving the Brazilian population of older adults.

Impaired generation of new subcategories and switching in a semantic verbal fluency test in older adults with mild cognitive impairment.

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

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

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

Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.

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

Tétano no Brasil: doença do idoso? / Tetanus in Brazil: a disease of the elderly?

No Brasil, a distribuiçäo etária do tétano é pouco estudada. Neste trabalho foi analisada a evoluçäo histórica do coeficiente de mortalidade por tétano no Brasil, entre 1980 e 1991, e estabelecida a distribuiçäo dos casos pela faixa etária, tendo por base o Sistema de Informaçöes de Mortalidade. Os coeficientes de mortalidade por faixa etária foram calculados conforme os dados fornecidos pela FUNASA-CENEPI, DATASUS e IBGE. Utilizou-se o teste qui-quadrado para comparar os coeficientes de mortalidade para as diversas faixas etárias, por ano e regiäo do país. Houve declínio dos coeficientes de mortalidade em todas as faixas etárias, exceto nos idosos. Nas regiöes Norte e Sul houve aumento do coeficiente de mortalidade nos idosos. No Brasil, o tétano vem apresentando comportamento epidemiológico semelhante ao observado oos países desenvolvidos, onde os idosos representam o principal grupo de risco para adoecer e morrer da doença