Alzheimer Disease: Bottino CM

Nitrini R, Caramelli P, Bottino CM, Damasceno BP, Brucki SM, Anghinah R, Anonymous00265. · Departamento Científico de Neurologia Cognitiva e do Envelhecimento, Academia Brasileira de Neurologia, Brazil. · Arq Neuropsiquiatr. · Pubmed #16172733 links to  free full text

Abstract: The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimer's 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.

Nitrini R, Caramelli P, Bottino CM, Damasceno BP, Brucki SM, Anghinah R, Anonymous00264. · Departamento Científico de Neurologia Cognitiva e do Envelhecimento, Academia Brasileira de Neurologia, Brazil. · Arq Neuropsiquiatr. · Pubmed #16172732 links to  free full text

Abstract: This panel had the objective of recommending evidence-based guidelines for the clinical diagnosis of Alzheimer's 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-thyroxine, 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.

Marchetti RL, Bottino CM, Azevedo D, Marie SK, de Castro CC. · Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo. · Arq Neuropsiquiatr. · Pubmed #12131944 links to  free full text

Abstract: RATIONALE: The development of reliable techniques for volumetric measurement of mesial temporal structures (amygdala, hippocampus and parahippocampal gyrus) on magnetic resonance imaging (MRI) can provide data for the study of neuropsychiatric disorders, mainly temporal lobe epilepsy, Alzheimer's disease and schizophrenia. METHOD: We investigated these techniques performing intraobserver and interobserver reliability study concerning normal controls, epilepsy and Alzheimer's disease patients using the intra-class correlation coefficient. RESULTS: Intra-observer reliability of evaluated structures ranged from 0.93 to 0.99 (p<0.001). Inter-observer reliability ranged from 0.70 to 0.95 (p < or = 0.001). CONCLUSION: The results suggest that the technique of MRI morphometry of mesial temporal regions can be considered a reliable tool which may help in the investigation of neuropsychiatric disorders, since used by adequately trained clinicians and researchers.

Azevedo D, Tatsch M, Hototian SR, Bazzarella MC, Castro CC, Bottino CM. · Old Age Research Group, Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. · Dement Geriatr Cogn Disord. · Pubmed #18441524 No free full text.

Abstract: OBJECTIVE: To describe the findings of proton magnetic resonance spectroscopy ((1)H-MRS) in Alzheimer's disease (AD) and cognitive impairment, no dementia (CIND) elderly from a community-based sample. METHODS: Thirteen patients with AD, 12 with CIND and 15 normal individuals were evaluated. The (1)H-MRS was performed in the right temporal, left parietal and medial occipital regions studying the metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (mI). The clinical diagnosis was based on standardized cognitive tests - MMSE and CAMDEX - and the results correlated with the (1)H-MRS. RESULTS: Parietal Cho was higher in control individuals and lower in CIND subjects. AD and control groups were better identified by temporal and parietal mI combined with the temporal NAA/Cr ratio. CIND was better identified by parietal Cho. CONCLUSION: The (1)H-MRS findings confirmed the hypothesis that metabolic alterations are present since the first symptoms of cognitively impaired elderly subjects. These results suggest that combining MRS from different cerebral regions can help in the diagnosis and follow-up of community elderly individuals with memory complaints and AD.

Bottino CM, Azevedo D, Tatsch M, Hototian SR, Moscoso MA, Folquitto J, Scalco AZ, Bazzarella MC, Lopes MA, Litvoc J. · Old Age Research Group (PROTER), Institute and Department of Psychiatry, University of São Paulo, São Paulo, Brazil. · Dement Geriatr Cogn Disord. · Pubmed #18843181 No free full text.

Abstract: 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.

Avila R, Carvalho IA, Bottino CM, Miotto EC. · Old Age Research Group (PROTER), Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil. · Behav Neurol. · Pubmed #18430980 No free full text.

Abstract: OBJECTIVE: The purpose of this study was to analyze the effect of a neuropsychological rehabilitation (NR) program on patients with Alzheimer's disease (AD). METHODS: The sample was composed of 16 elderly outpatients who participated in an open trial with rivastigmine (6 to 12 mg/day) for 4 months and were randomized to 3 different groups: 1. group NR (N=5), 2. individualized NR (N=6) and 3. NR at home under supervision of a relative or caregiver (N=5). All 3 groups fulfilled the same NR protocol consisting of a once a week session. Just before and after the 22 week period of rehabilitation, all patients were evaluated using psychiatric and functional scales, and neuropsychological tests by interviewers that did not participate in the cognitive training. RESULTS: The intervention did not produce any statistically significant change, but small gains were observed on some cognition tests, activities of daily living (ADL), and psychiatric symptoms in groups 1 and 2. CONCLUSION: Group NR is recommended for reducing psychiatric symptoms, and individualized NR for improving ADL. NR at home either has no associated benefits, or the training sessions were not appropriately conducted by the caregiver. However, additional research with larger samples is necessary to confirm these observations.

Tatsch MF, Bottino CM, Azevedo D, Hototian SR, Moscoso MA, Folquitto JC, Scalco AZ, Louzã MR. · Old Age Research Group (PROTER), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. · Am J Geriatr Psychiatry. · Pubmed #16670248 No free full text.

Abstract: OBJECTIVES: The objectives of this study were to describe the prevalence of neuropsychiatric symptoms of dementia in Alzheimer disease (AD) and cognitively impaired nondemented (CIND) subjects from a community-based Brazilian sample and to correlate these symptoms with severity of cognitive deficits. METHOD: A total of 1,563 randomly selected subjects were evaluated with the following screening tests: Mini-Mental Status Examination, Fuld Object Memory Evaluation, Informant Questionnaire on Cognitive Decline in the Elderly, and Activities of Daily Living-International Scale. Screen positives were submitted to a workup for dementia, physical and neurologic examination, cranial computed tomography or cerebral magnetic resonance imaging, the Cambridge Examination for Mental Disorders, Clinical Dementia Rating Scale (CDR), and the Neuropsychiatric Inventory (NPI). Diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: Sixty patients with AD, 25 CIND, and 78 healthy elderly subjects were evaluated. Informants reported that 78.33% of patients with AD had one or more neuropsychiatric symptoms. Apathy (53.33%), depression (38.33%), sleep alterations (38.33%), and anxiety (25%) were the most prevalent disturbances in AD subjects. These disturbances were more prevalent in patients with AD than in the comparison group and CIND individuals. In the CIND group, the most frequent neuropsychiatric symptoms were anxiety and sleep alterations (both with 24%) followed by depression (16%). Total NPI scores were significantly different between AD and CIND groups, AD and comparison groups, and CIND and the comparison group. Apathy was the only neuropsychiatric symptom that was significantly different between the groups divided according to the CDR being more frequent in subjects with moderate to severe dementia. CONCLUSIONS: Neuropsychiatric symptoms seem to be as common in patients living in a developing country as they are in demented patients from the developed world. Indeed, the fact that some of our results are similar to other population-based studies may suggest that cultural factors play a minor role in the emergence of these symptoms, at least in a Latin American country like Brazil.

Azevedo D, Bottino CM, Tatsch M, Hototian SR, Bazzarella MC, Castro CC. · Projeto Terceira Idade (PROTER), Instituto e Departamento de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, SP, Brasil. · Arq Neuropsiquiatr. · Pubmed #16400423 links to  free full text

Abstract: OBJECTIVE: To describe the proton magnetic resonance spectroscopy (1H-ERM) data in Alzheimer's disease (AD) and Cognitive Impairment Not Dementia (CIND) in a community sample. METHOD: We investigated subjects with AD (n=6), CIND (n=7) and normal control (n=7). 1H-ERM was performed with single voxel (8 cm3) placed in temporal, parietal and occipital regions and studied metabolites were: N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI). RESULTS: NAA concentration was higher in control subjects than AD and intermediated in CIND patients. Cho parietal plus occipital and Cr parietal plus Cho occipital classified correctly 92.3% of subjects Control vs AD. Temporal mI classified 78.6% of subjects between Control vs CIND. CONCLUSION: Spectroscopy can be used in the diagnosis and follow-up of individuals with cognitive impairment; evaluation of community subjects may show different patterns of brain metabolites distribution.

Bottino CM, Carvalho IA, Alvarez AM, Avila R, Zukauskas PR, Bustamante SE, Andrade FC, Hototian SR, Saffi F, Câmargo CH. · Old Age Research Group (PROTER), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil. · Clin Rehabil. · Pubmed #16323385 No free full text.

Abstract: OBJECTIVE: To study the efficacy of cognitive rehabilitation combined with acetylcholinesterase inhibitor (AChE-I) treatment in patients with mild Alzheimer's disease and their relatives. METHOD: Thirteen patients with mild Alzheimer's disease treated with rivastigmine 6-12 mg/day for more than two months started cognitive rehabilitation training. Before and after the cognitive rehabilitation training patients were assessed through cognitive tests, activities of daily living scale, neuropsychological battery and scales to evaluate caregivers' depressive and anxiety symptoms. Six patients were randomized to a combined treatment group (AChE-I plus cognitive rehabilitation and caregiver support) and seven patients to a control group (AChE-I only) and followed up for five months. RESULTS: Mini-Mental State Examination (MMSE) scores (p = 0.047) and backward digit span scores (p = 0.018) were significantly different between the groups on follow-up. The combined treatment group showed a better positive treatment effect on cognitive and neuropsychological tests applied to patients and reduction of psychiatric symptoms was observed in their caregivers (nonsignificant). CONCLUSION: Cognitive rehabilitation associated with AChE-I treatment can potentially be useful to stabilize or improve cognitive and functional performance of patients with mild Alzheimer's disease and can reduce caregivers' psychiatric symptoms.

Avila R, Bottino CM, Carvalho IA, Santos CB, Seral C, Miotto EC. · Projeto Terceira Idade, Instituto de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil. · Braz J Med Biol Res. · Pubmed #15517089 links to  free full text

Abstract: Patients with Alzheimer's disease (AD) gradually lose their cognitive competence, particularly memory, and the ability to perform daily life tasks. Neuropsychological rehabilitation is used to improve cognitive functions by facilitating memory performance through the use of external aids and internal strategies. The effect of neuropsychological rehabilitation through memory training - motor movements, verbal association, and categorization - and activities of daily living (ADL) training was tested in a sample of 5 elderly out-patients (mean age: 77.4 +/- 2.88 years), with mild AD (Mini-Mental State Examination score: 22.20 +/- 2.17) and their caregivers. All patients had been taking rivastigmine (6-12 mg/day) for at least 3 months before being assigned to the rehabilitation sessions, and they continued to take the medication during the whole program. Just before and after the 14-week neuropsychological rehabilitation program all patients were assessed by interviewers that did not participate in the cognitive training, using the Mini-Mental State Examination, Montgomery-Alsberg Depression Rating Scale, Hamilton Anxiety Scale, Interview to Determine Deterioration in Functioning in Dementia, Functional Test, Memory Questionnaire of Daily Living for patient and caregiver, Quality of Life Questionnaire for patient and caregiver, and a neuropsychological battery. The results showed a statistically significant improvement in ADL measured by Functional Test (P = 0.04), and only a small improvement in memory and psychiatric symptoms. Our results support the view that weekly stimulation of memory and training of ADL is believed to be of great value in AD treatment, not only delaying the progress of the disease, but also improving some cognitive functions and ADL, even though AD is a progressively degenerative disease.

Gattaz WF, Forlenza OV, Talib LL, Barbosa NR, Bottino CM. · Laboratory of Neuroscience, University of São Paulo, Brazil. · J Neural Transm. · Pubmed #15088152 No free full text.

Abstract: Phospholipase A(2) (PLA(2)) controls the metabolism of phospholipids in cell membranes. In the brain, PLA(2) influences the processing of the amyloid precursor protein (APP) and thus the production of the amyloid-beta peptides (Abeta), which are the major components of the senile plaques in Alzheimer's disease (AD). Reduced PLA(2) activity has been reported in brain and in platelets of AD patients. In the present study we investigated PLA(2) activity in platelets from 21 AD patients as compared to 17 healthy elderly controls and 11 individuals with mild cognitive impairment (MCI). Subjects were cognitively assessed by the Mini-Mental State Examination (MMSE) and the CAMDEX schedule. Platelet PLA(2) activity was determined by radio-enzymatic assay, which mainly detected a calcium-independent form of the enzyme present also in the brain (iPLA(2)). PLA(2) activity was significantly lower in AD than in controls (p < 0.001). Mean PLA(2) activity in MCI individuals was between the values of AD patients and controls, with a subgroup showing PLA as low as the lowest AD patients, but the differences from MCI were not significant from AD and control groups. Lower PLA(2) activity was significantly correlated with a worse cognitive performance both at the MMSE (p = 0.001) and the cognitive sub-scale of the CAMDEX inventory (p = 0.002). Our data replicate previous findings of reduced platelet PLA(2) activity in AD. Both reduced PLA(2) activity and the correlation with impaired cognition were also reported in brain tissue of AD patients, suggesting thus that the present determinations in platelets may be related to a reduction in the brain. In the brain the inhibition of PLA(2) inhibits the physiological secretion of the APP, a mechanism that increases Abeta formation. Further longitudinal studies should investigate whether those MCI individuals with the lowest PLA(2) values in platelets would be at a higher risk to develop AD during a longitudinal follow up.

Busatto GF, Garrido GE, Almeida OP, Castro CC, Camargo CH, Cid CG, Buchpiguel CA, Furuie S, Bottino CM. · Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. · Neurobiol Aging. · Pubmed #12498956 No free full text.

Abstract: Several MRI studies have reported reductions in temporal lobe volumes in Alzheimer's disease (AD). Measures have been usually obtained with regions-of-interest (ROI) drawn manually on selected medial and lateral portions of the temporal lobes, with variable choices of anatomical borders across different studies. We used the fully automated voxel-based morphometry (VBM) approach to investigate gray matter abnormalities over the entire extension of the temporal lobe in 14 AD patients (MMSE 14-25) and 14 healthy controls. Foci of significantly reduced gray matter volume in AD patients were detected in both medial and lateral temporal regions, most significantly in the right and left posterior parahippocampal gyri and the left posterior inferior temporal gyrus/fusiform gyrus (P<0.05, corrected for multiple comparisons). At a more flexible statistical threshold (P<0.001, uncorrected for multiple comparisons), circumscribed foci of significant gray matter reduction were also detected in the right amygdala/enthorinal cortex, the anterior and posterior borders of the superior temporal gyrus bilaterally, and the anterior portion of the left middle temporal gyrus. These VBM results confirm previous findings of temporal lobe atrophic changes in AD, and suggest that these abnormalities may be confined to specific sites within that lobe, rather than showing a widespread distribution.

Garrido GE, Furuie SS, Buchpiguel CA, Bottino CM, Almeida OP, Cid CG, Camargo CH, Castro CC, Glabus MF, Busatto GF. · Division of Informatics, Heart Institute (InCor), University of São Paulo Medical School, Brazil. · J Neurol Neurosurg Psychiatry. · Pubmed #12397142 links to  free full text

Abstract: 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.

Bottino CM, Castro CC, Gomes RL, Buchpiguel CA, Marchetti RL, Neto MR. · Institute and Department of Psychiatry, University of São Paulo School of Medicine, Brazil. · Int Psychogeriatr. · Pubmed #12094908 No free full text.

Abstract: BACKGROUND: Volumetric magnetic resonance imaging (MRI) has been extensively studied in the last decade as a method to help with the clinical diagnosis of Alzheimer's 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.

Bottino CM, Carvalho IA, Alvarez AM, Avila R, Zukauskas PR, Bustamante SE, Andrade FC, Hototian SR, Saffi F, Camargo CH. · Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brasil. · Arq Neuropsiquiatr. · Pubmed #11965412 links to  free full text

Abstract: OBJECTIVE: This study aims to show preliminary results of the 'combined treatment' (acetylcholinesterase inhibitor + cognitive training) on a group of mild Alzheimer's disease (AD) patients, followed-up for 7 months. METHODS: Six mild AD patients, diagnosed according to ICD-10 and NINCDS-ADRDA criteria, were included on a open trial with Rivastigmine, 6-12 mg/day, for 2 months, followed by a weekly cognitive rehabilitation group, for 5 months. Caregivers were submitted to a weekly group of counseling and support for 5 months. RESULTS: Stabilization or mild improvement of patients' cognitive and activities of daily living deficits were found, besides reduction of patients and caregivers' depressive and anxiety levels. CONCLUSION: The 'combined treatment' can help on the stabilization or result on a mild improvement of AD patients' cognitive and functional deficits. Support and counseling interventions can reduce the levels of caregivers' psychiatric symptoms.

Lopes MA, Bottino CM. · Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brasil. · Arq Neuropsiquiatr. · Pubmed #11965411 links to  free full text

Abstract: 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 Alzheimer's 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.