Edgar Nunes de Moraes

Clinical Applicability and Cutoff Values for an Unstructured Neuropsychological Assessment Protocol for Older Adults with Low Formal Education

Background and Objectives The neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use. Methods and Results A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living. Conclusion The study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education.

Ascorbic acid, alpha-tocopherol, and beta-carotene reduce oxidative stress and proinflammatory cytokines in mononuclear cells of Alzheimer's disease patients.

Abstract Objectives The in vitro effect of a vitamin complex in generating and reducing oxidative species in peripheral blood mononuclear cells (PBMNC) and plasma of patients with Alzheimers disease (AD) and healthy subjects (HS) was evaluated. Methods Two concentrations of a vitamin complex ([A] and [20A]) with ascorbic acid, alpha-tocopherol, and beta-carotene were incubated with either mononuclear cells or plasma. The generation of oxidizing species was measured in a luminol-dependent chemiluminescence assay and the reducing response by the MTT dye reduction assay. The levels of cytokines (interleukin [IL]-1β, IL-6, and IL-4) were measured by sandwich enzyme-linked immunosorbent assay. Results Our results demonstrated that the increase in the vitamin complex concentration reduced the reactive oxygen species (ROS) production and enhanced cellular reduction capacity in cells of AD patients in concentration [20A]. Plasma reduction capacity rose significantly for both groups (AD and HS). Concentration [A] did not alter the IL-1β production, increased IL-4 production in both groups and lowered IL-6 production in AD cells. Concentration [20A] increased pro-inflammatory cytokines (IL-1β and IL-6) and decreased IL-4 production by PBMNC of HS leading to a pro-inflammatory status. Discussion The antioxidant vitamin complex was effective in reducing oxidative stress in PBMNC of AD patients by lowering ROS production, improving cellular antioxidant capacities and modifying cytokine induced inflammation.

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.

Tetanus in Brazil: a disease of the elderly?

Epidemiological data regarding the age distribution of tetanus in Brazil is scarce. This work analyzed the historical evolution of tetanus in Brazil, between 1980 and 1991, according to the Mortality Information System and established the age distribution for this disease. The data used was that provided by FUNASA-CENEPI, DATASUS and IBGE. Between 1980 and 1991, the coefficient of general incidence dropped from 2.6 to 1.0 case per 100,000 inhabitants. There was a decline in the mortality coefficients within all the age groups, except in the elderly. In the North and South regions, there was an increase in the mortality coefficient among the elderly. Infantile tetanus is disappearing, particularly, in the developed areas. However, the overall lethality tended to rise in this period and, in 1991, it reached 32.5%. In Brazil, tetanus presents epidemic behavior similar to that observed in the developed countries, where the elderly represent the main risk group to contract and die from the disease.

Mapping the clockworks: what does the Clock Drawing Test assess in normal and pathological aging?

The Clock Drawing Test (CDT) is a cognitive screening tool used in clinical and research settings. Despite its role on the assessment of global cognitive functioning, the specific cognitive components required for test performance are still unclear. We aim to assess the role of executive functioning, global cognitive status, visuospatial abilities, and semantic knowledge on Shulmans CDT performance. Fifty-three mild cognitive impairment, 60 Alzheimers dementia, and 57 normal elderly controls performed the CDT, the Frontal Assessment Battery, the Mini-Mental State Examination, the Stick Design Test, and a naming test (TN-LIN). An ordinal regression assessed specific neuropsychological influences on CDT performance. All the cognitive variables were related to the CDT, accounting for 53% of variance. The strongest association was between the CDT and executive functions, followed by global cognitive status, visuospatial processing, and semantic knowledge. Our result confirms the multidimensional nature of the test and the major role of executive functions on performance.

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.

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 Alzheimers disease, the results are not always consistent. This study aimed to compare clustering and switching measures of an animals 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 Alzheimers 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.

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.

Elderly patients attended in emergency health services in Brazil: a study for victims of falls and traffic accidents

The article aims to describe the profile of elderly victims of falls and traffic accidents from the data of the Surveillance Survey of Violence and Accidents (VIVA). The VIVA Survey was conducted in the emergency health-services of the Unified Health System in the capitals of Brazil in 2011. The sample of elderly by type of accident was subjected to the two-step cluster procedure. Of the 2463 elderly persons in question, 79.8% suffered falls and 20.2% were the victims of traffic accidents. The 1812 elderly who fell were grouped together into 4 clusters: Cluster 1, in which all had disabilities; Cluster 2, all were non-white and falls took place in the home; Cluster 3, younger and active seniors; and Cluster 4, with a higher proportion of seniors 80 years old or above who were white. Among cases of traffic accidents, 446 seniors were grouped into two clusters: Cluster 1 of younger elderly, drivers or passengers; Cluster 2, with higher age seniors, mostly pedestrians. The main victims of falls were women with low schooling and unemployed; traffic accident victims were mostly younger and male. Complications were similar in victims of falls and traffic accidents. Clusters allow adoption of targeted measures of care, prevention and health promotion.