Cássio M.C. Bottino

Prevalence of dementia in Latin America: a collaborative study of population-based cohorts

BACKGROUND Dementia is becoming a major public health problem in Latin America (LA), yet epidemiological information on dementia remains scarce in this region. This study analyzes data from epidemiological studies on the prevalence of dementia in LA and compares the prevalence of dementia and its causes across countries in LA and attempts to clarify differences from those of developed regions of the world. METHODS A database search for population studies on rates of dementia in LA was performed. Abstracts were also included in the search. Authors of the publications were invited to participate in this collaborative study by sharing missing or more recent data analysis with the group. RESULTS Eight studies from six countries were included. The global prevalence of dementia in the elderly (> or =65 years) was 7.1% (95% CI: 6.8-7.4), mirroring the rates of developed countries. However, prevalence in relatively young subjects (65-69 years) was higher in LA studies The rate of illiteracy among the elderly was 9.3% and the prevalence of dementia in illiterates was two times higher than in literates. Alzheimers disease was the most common cause of dementia. CONCLUSIONS Compared with studies from developed countries, the global prevalence of dementia in LA proved similar, although a higher prevalence of dementia in relatively young subjects was evidenced, which may be related to the association between low educational level and lower cognitive reserve, causing earlier emergence of clinical signs of dementia in the LA elderly population.

Diagnóstico de doença de Alzheimer no Brasil: avaliação cognitiva e funcional. Recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimers disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended.The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimers disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended.

Cognitive intervention in amnestic Mild Cognitive Impairment: a systematic review.

Mild Cognitive Impairment (MCI) represents a transitional state between normal aging and early dementia and is commonly associated with memory impairment (amnestic or A-MCI). Several studies have investigated therapeutic approaches to A-MCI, including cholinestherase inhibitors (I-ChEs), although this practice is still controversial. Thus, there is a current need to determine the effects of cognitive interventions either in combination with I-ChEs or alone. To assess the efficacy of such treatments, neuropsychological instruments and self-evaluated scoring of memory, mood, daily life activities and quality of life are employed. Recently, some studies have used functional magnetic resonance imaging (fMRI) in order to understand the neurobiological effects of these interventions. The aim of this systematic review is to investigate the effectiveness of cognitive interventions on the enhancement of learning abilities as well as their impacts on cognitive measurements of mood, everyday functioning and functional neuroimaging. This review also focused on the methodological aspects of such studies and attempted to introduce new perspectives on cognitive interventions in this population. The authors concluded that a-MCI patients are capable to learn new information and memory strategies. Although findings in standardized neuropsychological tests are limited, non-standardized cognitive measures and subjective measures show significant changes. Furthermore, fMRI reveals changes in the patterns of brain activation and increase of connectivity.

Volumetric MRI measurements can differentiate Alzheimer's disease, mild cognitive impairment, and normal aging.

BACKGROUND Volumetric magnetic resonance imaging (MRI) has been extensively studied in the last decade as a method to help with the clinical diagnosis of Alzheimers disease (AD). In recent years, researchers have also started investigating if that technique would be useful to identify individuals with mild cognitive impairment (MCI), differentiating them from AD patients and from normal elderly controls. This research project was planned to assess the accuracy of volumetric MRI to differentiate those groups of individuals. METHOD The investigation involved 39 patients with diagnosis of mild to moderate dementia in AD, according to the criteria of the NINCDS-ADRDA, DSM-III-R, and ICD-10; 21 subjects with complaints of cognitive decline without other psychiatric disorders (MCI); and 20 normal elderly controls. All the subjects were submitted to a standard protocol, including volumetric MRI evaluations. RESULTS The results indicated that all regions of interest measured (amygdala, hippocampus, and parahippocampal gyrus) were significantly different (p < .005) in AD patients compared to MCI subjects and controls. The left volumetric measures (amygdala, hippocampus, and parahippocampal gyrus) were also significantly different between the MCI subjects and controls (p < .05). The discriminant function analysis correctly classified 88.14% of the AD patients and controls, 81.67% of AD patients and MCI subjects, and 80.49% of the MCI subjects and controls. CONCLUSIONS The results suggest that measures of medial temporal lobe regions are useful to identify mild to moderate AD patients and MCI subjects, separating them from normal elderly individuals.

Peripheral Oxidative Stress Biomarkers in Mild Cognitive Impairment and Alzheimer's Disease

Oxidative stress has been associated with normal aging and Alzheimers disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = -0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = -0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders.

Prevalência de demência em diversas regiões do mundo: Análise dos estudos epidemiológicos de 1994 a 2000

OBJECTIVE To analyse the prevalence studies of dementia from 1994 to 2000. METHODS The papers were searched on Medline and Lilacs and the inclusion criteria were: to be an original study, that estimated dementia prevalence and investigated community samples. RESULTS thirty-eight studies were evaluated from all continents. The mean age-specific prevalence rates of dementia were 1,17% for the 65-69 years group, and 54,83% over 95 years. The results were strongly influenced by age. Dementia prevalence rates were higher on women on 75% of the papers reviewed. The Alzheimers disease/vascular dementia ratio was higher in South America and lower in Asia. DISCUSSION Methodological advances were found, specially regarding the homogeneity of diagnostic criteria. The effect of age on the rates of dementia prevalence was pronounced, up to 90 years of age.OBJECTIVE: To analyse the prevalence studies of dementia from 1994 to 2000. METHODS: The papers were searched on Medline and Lilacs and the inclusion criteria were: to be an original study, that estimated dementia prevalence and investigated community samples. RESULTS: thirty-eight studies were evaluated from all continents. The mean age-specific prevalence rates of dementia were 1,17% for the 65-69 years group, and 54,83% over 95 years. The results were strongly influenced by age. Dementia prevalence rates were higher on women on 75% of the papers reviewed. The Alzheimers disease/vascular dementia ratio was higher in South America and lower in Asia. DISCUSSION: Methodological advances were found, specially regarding the homogeneity of diagnostic criteria. The effect of age on the rates of dementia prevalence was pronounced, up to 90 years of age.

Estimate of Dementia Prevalence in a Community Sample from São Paulo, Brazil

Aims: To estimate dementia prevalence and describe the etiology of dementia in a community sample from the city of São Paulo, Brazil. Methods: A sample of subjects older than 60 years was screened for dementia in the first phase. During the second phase, the diagnostic workup included a structured interview, physical and neurological examination, laboratory exams, a brain scan, and DSM-IV criteria diagnosis. Results: Mean age was 71.5 years (n = 1,563) and 58.3% had up to 4 years of schooling (68.7% female). Dementia was diagnosed in 107 subjects with an observed prevalence of 6.8%. The estimate of dementia prevalence was 12.9%, considering design effect, nonresponse during the community phase, and positive and negative predictive values. Alzheimer’s disease was the most frequent cause of dementia (59.8%), followed by vascular dementia (15.9%). Older age and illiteracy were significantly associated with dementia. Conclusions: The estimate of dementia prevalence was higher than previously reported in Brazil, with Alzheimer’s disease and vascular dementia being the most frequent causes of dementia. Dementia prevalence in Brazil and in other Latin American countries should be addressed by additional studies to confirm these higher dementia rates which might have a sizable impact on countries’ health services.

Instrumentos combinados na avaliação de demência em idosos: resultados preliminares

ABSTRACT - Objective : To determine if a functional scale combined with a cognitive test would improve thediagnostic accuracy of dementia. Method : Thirty patients with mild to moderate dementia, diagnosed accordingto ICD-10 and DSM-III-R criteria, and 46 elderly controls, divided into three groups according to theirsocioeconomic status and educational level (high, medium and low) were investigated. The subjects wereassessed with the MMSE, and their informants were assessed with the scales IQCODE and B-ADL. Results : Onthe logistic regression, the MMSE isolated classified correctly 86.8% of patients and controls (80% sensitivityand 91.3% specificity). The combination MMSE + IQCODE classified correctly 92.1% of the subjects (83.3%sensitivity and 97.8% specificity), and the combination MMSE + B-ADL classified correctly 92.1% of subjects(86.7% sensitivity and 95.7% specificity). Conclusion : The results suggest that the combination of a cognitivetest with a functional scale can improve the detection of mild to moderate cases of dementia even on samplesof a very heterogeneous population regarding its socioeconomic status and educational level, as the Brazilian.KEY WORDS: dementia, diagnosis, cognitive test, functional scales.

Diagnóstico de doença de Alzheimer no Brasil: critérios diagnósticos e exames complementares. Recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

This panel had the objective of recommending evidence-based guidelines for the clinical diagnosis of Alzheimers disease (AD) in Brazil. Guidelines from other countries and papers on the diagnosis of AD in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. The panel concluded that dementia diagnosis should be based on the DSM criteria and AD diagnosis, on the McKhann et al. criteria (NINCDS-ADRDA). The recommended auxiliary tests are: blood cell count, blood urea nitrogen, serum levels of creatinine, free-tyroxine, thyroid-stimulant hormone, albumin, hepatic enzymes, vitamin B12 and calcium, serological tests for syphilis and, for those aged less than 60 years, serological tests for HIV. Cerebrospinal fluid examination is recommended in special situations. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory and has the main objective of excluding other diseases. SPECT and EEG are optional diagnostic methods.

Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer’s disease: a combined MRI and SPECT study

Objective: To investigate the relation between atrophy of the hippocampal region and brain functional patterns during episodic memory processing in Alzheimer’s disease. Patients and methods: Whole brain structural magnetic resonance imaging (MRI) data and single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF) were obtained during a verbal recognition memory task in nine subjects with mild Alzheimer’s disease and 10 elderly healthy controls. Using the statistical parametric mapping approach, voxel based comparisons were made on the MRI data to identify clusters of significantly reduced grey matter concentrations in the hippocampal region in the Alzheimer patients relative to the controls. The mean grey matter density in the voxel cluster of greatest hippocampal atrophy was extracted for each Alzheimer subject. This measure was used to investigate, on a voxel by voxel basis, the presence of significant correlations between the degree of hippocampal atrophy and the rCBF SPECT measures obtained during the memory task. Results: Direct correlations were detected between the hippocampal grey matter density and rCBF values in voxel clusters located bilaterally in the temporal neocortex, in the left medial temporal region, and in the left posterior cingulate cortex during the memory task in the Alzheimer’s disease group (p < 0.001). Conversely, measures of hippocampal atrophy were negatively correlated with rCBF values in voxel clusters located in the frontal lobes, involving the right and left inferior frontal gyri and the insula (p < 0.001). Conclusions: Hippocampal atrophic changes in Alzheimer’s disease are associated with reduced functional activity in limbic and associative temporal regions during episodic memory processing, but with increased activity in frontal areas, possibly on a compensatory basis.