Ricardo Nitrini

Sugestões para o uso do mini-exame do estado mental no Brasil

Mini-metal state examination (MMSE) is a screening test to detect cognitive impairment. The objectives of the present study are to describe some adaptations for use of MMSE in Brazil and to propose rules for its uniform application. METHOD: We evaluated 433 healthy subjects using the MMSE and verified the possible influence of demographic variables on total scores. RESULTS: Educational level was the main factor that influenced performance, demonstrated by ANOVA: F(4,425) = 100.45, p<0.0001. The median values for educational groups were: 20 for illiterates; 25 for 1 to 4 yrs; 26.5 for 5 to 8 yrs; 28 for 9 to 11 yrs and 29 for higher levels. CONCLUSION: The MMSE is an excellent screening instrument and definitive rules are necessary for comparison purposes.

Epidemiologic survey of dementia in a community-dwelling Brazilian population

The authors report the prevalence of dementia in a community-dwelling Brazilian elderly population and correlate prevalence data with educational and socioeconomic levels. The study was conducted in Catanduva, Brazil. A total of 1,656 randomly selected subjects aged 65 years or more were submitted to a health questionnaire, the Mini-Mental State Examination (MMSE), and the Pfeffer Functional Activities Questionnaire (PFAQ). According to the PFAQ and MMSE scores, selected subjects were submitted to clinical, neurologic, and cognitive evaluations. The subjects diagnosed with dementia underwent laboratory tests and brain computed tomography (CT). Dementia was diagnosed in 118 subjects, corresponding to a prevalence of 7.1%. The main clinical diagnoses were Alzheimer disease (AD; 55.1%), vascular dementia (9.3%), and AD with cerebrovascular disease (14.4%). The prevalence increased with age and was higher in women. There was an inverse association with education (3.5% among persons with 8 or more years of schooling to 12.2% among those who were illiterate). Multivariate analysis disclosed significant association between these three variables and dementia. The prevalence of dementia in this Brazilian population was 7.1%, and AD was the most frequent diagnosis. Age, female gender, and low educational level were significantly associated with a higher prevalence of dementia.

Performance of illiterate and literate nondemented elderly subjects in two tests of long-term memory

Cognitive evaluation in developing countries is a difficult undertaking due to low levels of schooling and particularly the illiteracy still frequent in the elderly. This study was part of the epidemiologic evaluation of dementia in Catanduva, Brazil, and had the objective of comparing the performance of illiterate and literate nondemented elderly individuals in 2 tests of long-term memory-the delayed recall of a word list from the CERAD and the delayed recall of common objects presented as simple drawings from the Brief Cognitive Screening Battery (BCSB). Fifty-one elderly subjects (23 illiterates) were evaluated, and the performance of the illiterates and literates differed in the CERAD memory test, but not in the BCSB memory test. This test may be more suitable for the assessment of long-term memory in populations with a high frequency of illiterates, and therefore might prove to be a useful screening tool for the diagnosis of dementia.

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.

Testes neuropsicológicos de aplicação simples para o diagnóstico de demência

Thirty patients with dementia defined by DSM-III-R criteria (Alzheimers disease (22), vascular dementia (3), Parkinsons disease, frontal lobe dementia, possible diffuse Lewy body dementia, normal pressure hydrocephalus and uncertain diagnosis), with scores below 24 points in the Mini-Mental Status Examination and more than 4 years of education were submitted to a neuropsychological evaluation. The scores in the neuropsychological tests were compared to those obtained by thirty normal volunteers paired for age, sex and education. Sensivity, specificity and accuracy of the tests in the distinction of demented and normal volunteers were determined. The accuracies were calculated using ROC curves. Blesseds information-memory-concentration test showed greatest accuracy, followed by copy of simple figures, delayed memory of 10 figures (after 5 minutes), recognition of 10 figures and verbal fluency test (animals). A linear discriminant function, composed by 6 tests: visual perception, incidental memory, delayed memory (after 5 minutes), drawing of a clock, verbal fluency (animals) and calculation tests, was able to discriminate all controls from patients and only one patient was wrongly classified as normal control. These tests were chosen because they can be applied in less than 10 minutes and are very easy to interpret. This discriminant function must be applied in another group of patients and controls in order to demonstrate its value. When associated to the MMSE it may be useful to discriminate patients with dementia from normal people in epidemiological studies.Thirty patients with dementia defined by DSM-III-R criteria (Alzheimers disease (22), vascular dementia (3), Parkinsons disease, frontal lobe dementia, possible diffuse Lewy body dementia, normal pressure hydrocephalus and uncertain diagnosis), with scores below 24 points in the Mini-Mental Status Examination and more than 4 years of education were submitted to a neuropsychological evaluation. The scores in the neuropsychological tests were compared to those obtained by thirty normal volunteers paired for age, sex and education. Sensitivity, specificity and accuracy of the tests in the distinction of demented and normal volunteers were determined. The accuracies were calculated using ROC curves. Blesseds information-memory-concentration test showed greatest accuracy, followed by copy of simple figures, delayed memory of 10 figures (after 5 minutes), recognition of 10 figures and verbal fluency test (animals). A linear discriminant function, composed by 6 tests: visual perception, incidental memory, delayed memory (after 5 minutes), drawing of a clock, verbal fluency (animals) and calculation tests, was able to discriminate all controls from patients and only one patient was wrongly classified as normal control. These tests were chosen because they can be applied in less than 10 minutes and are very easy to interpret. This discriminant function must be applied in another group of patients and controls in order to demonstrate its value. When associated to the MMSE it may be useful to discriminate patients with dementia from normal people in epidemiological studies.

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.

Illiteracy: The neuropsychology of cognition without reading

Illiterates represent a significant proportion of the worlds population. Written language not only plays a role in mediating cognition, but also extends our knowledge of the world. Two major reasons for illiteracy can be distinguished, social (e.g., absence of schools), and personal (e.g., learning difficulties). Without written language, our knowledge of the external world is partially limited by immediate sensory information and concrete environmental conditions. Literacy is significantly associated with virtually all neuropsychological measures, even though the correlation between education and neuropsychological test scores depends on the specific test. The impact of literacy is reflected in different spheres of cognitive functioning. Learning to read reinforces and modifies certain fundamental abilities, such as verbal and visual memory, phonological awareness, and visuospatial and visuomotor skills. Functional imaging studies are now demonstrating that literacy and education influence the pathways used by the brain for problem-solving. The existence of partially specific neuronal networks as a probable consequence of the literacy level supports the hypothesis that education impacts not only the individuals day-to-day strategies, but also the brain networks. A review of the issues related to dementia in illiterates is presented, emphasizing that the association between the education level and age-related cognitive changes and education remains controversial. The analysis of the impact of illiteracy on neuropsychological test performance represents a crucial approach to understanding human cognition and its brain organization under normal and abnormal conditions.

The dorsal raphe nucleus shows phospho-tau neurofibrillary changes before the transentorhinal region in Alzheimer's disease. A precocious onset?

Aims: Alzheimers disease (AD) is a progressive and irreversible disease. There is strong evidence that the progression of the phospho‐tau neurofibrillary cytoskeletal changes, rather than the β‐amyloid burden, is crucial in determining the severity of the dementia in AD. The Braak and Braak staging system (BB) focuses mainly on the cortical cytoskeletal pathology and classifies this progressive pathology into six stages, spreading from the transentorhinal region to primary cortices. Although it is reported elsewhere that the midbrains dorsal raphe nucleus (DR), which is connected with those areas of the cerebral cortex undergoing early changes during BB I and II, exhibits AD‐related cytoskeletal pathology, this nucleus has not been considered by the BB. Methods: To determine during which BB stage and how frequently the DR is affected by AD‐related neurofibrillary changes, we studied the DR of 118 well‐characterized individuals of the Brain Bank of the Brazilian Aging Brain Study Group categorized according to the BB. Thirty‐eight of these individuals were staged as BB = 0, and 80 as BB ≥ 1. Results: In all of the BB ≥ 1 individuals (cortical neurofibrillary changes were present at least in the transentorhinal region) and in more than 1/5 of the BB = 0 individuals neurofibrillary changes were detected in the supratrochlear subnucleus of the DR. Conclusions: These observations: (i) support the hypothesis of transneuronal spread of neurofibrillary changes from the DR to its interconnected cortical brain areas; and (ii) indicate that the supratrochlear subnucleus of the DR is affected by neurofibrillary changes before the transentorhinal cortex during the disease process underlying AD.

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.

Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains

IntroductionBrain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases.MethodsThe subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained.ResultsDuring the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at US