Alzheimer Disease: Caramelli P

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.

Machado JC, Caramelli P. · Aurus IEPE - Institute of Research and Education on Aging, Lucas Machado Foundation, Faculty of Medical Sciences of Minas Gerais, Belo Horizonte, Brazil. · Curr Opin Psychiatry. · Pubmed #17012934 No free full text.

Abstract: PURPOSE OF REVIEW: The aim of this article is to discuss new data on presently approved drugs for dementia, such as cholinesterase inhibitors and memantine, and concerns regarding the use of antipsychotics for treating neuropsychiatric symptoms, as well as to summarize some relevant studies recently published on emerging therapies with potential disease-modifying effects. RECENT FINDINGS: The main focuses of recent studies of cholinesterase inhibitors and memantine have been on efficacy and safety aspects in extended clinical trials, combined treatments or comparative analysis between agents, and also on potential neuroprotective effects and new indications. Other publications have assessed the evidence of efficacy and the increased risk of cerebrovascular events, rapid cognitive decline, and mortality with the use of antipsychotics in dementia, providing important information in relation to the controversy surrounding its use. Although more studies are warranted, a sizable literature on novel treatment options under investigation is currently available as a result of a better understanding of pathogenesis of dementia. SUMMARY: So far, there is no established method to predict better responders or long-term benefits with currently approved drugs for treatment of dementia. Recent systematic reviews and new research on current treatment, however, provide valuable information for clinicians, and novel drugs under investigation reveal promising new therapeutic strategies.

Teixeira AL, Caramelli P. · Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, 30180-120 Belo Horizonte, MG, Brasil. · Rev Bras Psiquiatr. · Pubmed #16816880 links to  free full text

Abstract: Apathy is the most common neuropsychiatry syndrome in Alzheimer's disease affecting 30-60% of patients. It can be defined as a loss of motivation and manifests in affect, cognition and behavioral changes, determining blunted emotional response, lack of insight and social retraction, respectively. In this paper, the clinical features and the therapeutic perspectives of apathy are presented. There is considerable overlap between apathy and depression in Alzheimer's disease, but both are considered discrete syndromes. Pharmacological interventions for apathy include psychostimulants, such as methylphenidate, dopaminergic agents and cholinesterase inhibitors, but the results are controversial and there is no established treatment.

Charchat-Fichman H, Caramelli P, Sameshima K, Nitrini R. · Departamento de Neurologia, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil. · Rev Bras Psiquiatr. · Pubmed #15867989 links to  free full text

Abstract: Decline of cognitive capacity (DCC) is due to normal physiological aging processes or to pre-dementia stage. Epidemiological studies show that elderly with decline of cognitive capacity have higher risk to develop Alzheimer's disease (AD), especially those with episodic memory deficits. This review presents the most important diagnosis criteria, neuropathological and neuropsychological findings of decline of cognitive capacity during aging.

Kawamoto EM, Munhoz CD, Glezer I, Bahia VS, Caramelli P, Nitrini R, Gorjão R, Curi R, Scavone C, Marcourakis T. · Department of Pharmacology, School of Medicine, University of São Paulo, São Paulo, Brazil. · Neurobiol Aging. · Pubmed #15718044 No free full text.

Abstract: Several studies have shown involvement of peroxynitrite anion, a potent oxidative agent, in Alzheimer's disease (AD) neuropathology. Herein, we assessed in platelets and erythrocytes of AD patients, age-matched and young adults controls: thiobarbituric acid-reactive substances (TBARS) production; superoxide dismutase (SOD), nitric oxide synthase (NOS) and Na,K-ATPase activities; cyclic GMP (cGMP) content, both basal and after sodium nitroprusside (SNP) stimulation. Aging was associated with an increase in TBARS production and NOS activity, a decrease in basal cGMP content and no change in SOD and Na,K-ATPase activities. AD patients, compared to aged controls, have: increase in TBARS production and in NOS, SOD and Na,K-ATPase activities but no alteration in basal cGMP content. SNP increased cGMP platelets production in all groups. In conclusion, we demonstrated in platelets and erythrocytes a disruption in systemic modulation of oxidative stress in aging and with more intensity in AD.

Caramelli P, Chaves ML, Engelhardt E, Machado JC, Schultz RR, Vale FA, Charchat-Fichman H, Anonymous00245. · Department of Neurology, University of São Paulo, São Paulo, SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #15273830 links to  free full text

Abstract: OBJECTIVE: To investigate the effects of galantamine on the performance of patients with mild to moderate Alzheimer's disease (AD) in a computerized neuropsychological test battery (CNTB). METHOD: Thirty-three patients with probable AD were treated with galantamine for three months and evaluated in a prospective, open-label, multi-center study. The CNTB and the ADAS-Cog were administered at baseline and after 12 weeks. The CNTB includes reaction time tests to evaluate attention, implicit and episodic memory for faces and words. Statistical comparisons were performed between the results in week 12 versus baseline. Patients who did not reach the therapeutic doses were excluded from the efficacy analysis. RESULTS: Four patients (12.1%) were excluded from the analysis either because of treatment discontinuation (n=3) or because a therapeutic dose was not reached (n=1). The remaining 29 patients were treated with doses of 24 mg/day (n=22) and 16 mg/day (n=7). After 12 weeks, significant reductions in reaction time were seen in the test of episodic memory for faces (p=0.023) and in the test of two-choice reaction time (p=0.039) of the CNTB. CONCLUSION: Treatment with galantamine produced improvement in computerized tests of attention and episodic memory after 12 weeks, leading to statistically significant reduction in the reaction times.

Nitrini R, Buchpiguel CA, Caramelli P, Bahia VS, Mathias SC, Nascimento CM, Degenszajn J, Caixeta L. · Department of Neurology, University of São Paulo School of Medicine, Brazil. · Acta Neurol Scand. · Pubmed #10705939 No free full text.

Abstract: OBJECTIVE: To investigate why bilateral parietotemporal hypoperfusion, the typical SPECT pattern of Alzheimer's disease (AD), occurs in some but not in all patients with probable AD. METHODS: We reviewed the SPECT scans of 220 patients presenting with cognitive impairment. Among them, 104 patients fulfilled NINCDS-ADRDA criteria for probable AD, 48 (32 women) with early onset (before age of 65) and 56 (40 women) with late onset of the symptoms. Dementia severity was assessed by the Mini-Mental State Examination. The SPECT scans were classified by visual inspection blind to clinical diagnoses. RESULTS: Bilateral parietotemporal hypoperfusion was more frequent in patients with severe AD, in those with early onset of the symptoms, and in men. Duration of symptoms, type of gamma-camera or radiopharmaceutical agent used were not associated with this SPECT pattern. CONCLUSION: These findings may be useful in the clinical setting and point to heterogeneity of AD according to age at onset.

de Souza-Talarico JN, Chaves EC, Nitrini R, Caramelli P. · Department of Medical-Surgical Nursing, School of Nursing, University of São Paulo, São Paulo, Brazil. · J Clin Nurs. · Pubmed #19077019 No free full text.

Abstract: AIM: To investigate stress intensity and coping style in older people with mild Alzheimer's disease. BACKGROUND: The potential risk assessment of a stress event and the devising of coping strategies are dependent on cognitive function. Although older individuals with Alzheimer's disease present significant cognitive impairment, little is known about how these individuals experience stress events and select coping strategies in stress situations. DESIGN: Survey. METHOD: A convenient sample of 30 cognitively healthy older people and 30 individuals with mild Alzheimer's disease were given an assessment battery of stress indicators (Symptom Stress List, Cornell Scale for Depression in Dementia, State-Trait Anxiety Inventory), coping style (Jalowiec Coping Scale) and cognitive performance (mini-mental state exam) were applied in both groups. Statistical analysis of the data employed the Mann-Whitney test to compare medians of stress indicators and coping style, Fischer's exact test to compare proportions when expected frequencies were lower than five, and Spearman's correlation coefficient to verify correlation between coping style and cognitive performance. RESULTS: Both groups suffered from the same stress intensity (p = 0.254). Regarding coping styles, although differences were not statistically significant (p = 0.124), emotion-oriented coping was predominant in the patients with Alzheimer's disease. However, those individuals displaying better cognitive performance in the Alzheimer's disease group had selected coping strategies focused on problem solving (p = 0.0074). CONCLUSIONS: Despite a tendency for older people with Alzheimer's disease to select escape strategies and emotional control, rather than attempting to resolve or lesser the consequences arising from a problem, coping ultimately depends on cognitive performance of the individual. RELEVANCE TO CLINICAL PRACTICE: The findings of this study provide information and data to assist planning of appropriate support care for individuals with Alzheimer's disease who experience stress situations, based on their cognitive performance.

Marcourakis T, Bahia VS, Kawamoto EM, Munhoz CD, Gorjão R, Artes R, Kok F, Caramelli P, Nitrini R, Curi R, Scavone C. · Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil. · Cell Biochem Funct. · Pubmed #18846579 No free full text.

Abstract: The presence of the epsilon4 allele of apolipoprotein E (APOE) is considered a risk factor for sporadic Alzheimer's disease (AD). Our recent data demonstrated that the systemic modulation of oxidative stress in platelets and erythrocytes is disrupted in aging and AD. In this study, the relationship between APOE genotype and oxidative stress markers, both in AD patients and controls, was evaluated. The AD group showed an increase in the content of thiobarbituric acid-reactive substances (TBARS) and in the activities of nitric oxide synthase (NOS) and Na, K-ATPase, when compared to controls. Both groups had a similar cGMP content and superoxide dismutase activity. APOE epsilon4 allele carriers showed higher NOS activity than non-carriers. These results suggest a possible influence of APOE genotype on nitric oxide (NO) production that might enhance the effects of age-related specific factor(s) associated with neurodegenerative disorders.

Bahia VS, Kok F, Marie SN, Shinjo SO, Caramelli P, Nitrini R. · Behavioral and Cognitive Neurology Unit, Department of Neurology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil. · Alzheimer Dis Assoc Disord. · Pubmed #18317248 No free full text.

Abstract: Alzheimer disease (AD) is the most frequent cause of dementia in Western countries. Putative genetic risk factors for AD are polymorphisms in the apolipoprotein E (APOE) gene and in the low-density lipoprotein receptor-related protein (LRP) gene. Our objective was to investigate the role of the APOE coding region polymorphisms epsilon 2, epsilon 3, and epsilon 4 and APOE promoter variants A/T at position -491 and G/T at -219, as well as LRP polymorphism C/T, as risk factors for AD in Brazilian individuals. One hundred and twenty patients with probable AD, along with 120 controls were analyzed. A significant difference between patients and controls for epsilon 4 alleles was observed: frequency of this allele in AD was 0.31, and 0.10 in controls. Individuals with 2 epsilon 4 alleles had a higher risk for AD than subjects with only 1 such allele; presence of 1 epsilon 2 allele proved protective. The presence of the T allele of the -219 polymorphism was also associated with an increased risk of AD, but this polymorphism is in linkage disequilibrium with APOE epsilon polymorphisms. No significant differences between patients and controls were observed for -491 APOE or LRP polymorphisms. In this Brazilian population, both the epsilon 4 allele and T -219 polymorphism were associated with an increased risk for AD.

Carthery-Goulart MT, Areza-Fegyveres R, Schultz RR, Okamoto I, Caramelli P, Bertolucci PH, Nitrini R. · Clínica Neurológica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #17952309 links to  free full text

Abstract: The original version of the Disability Assessment for Dementia (DAD) was translated into Portuguese and back translated to English. The divergences of translation were identified and discussed, resulting in a version that was used in a preliminary investigation for cross-cultural adaptation. The final version was administered to 29 patients with mild to moderate probable Alzheimer's disease. The correlation coefficients of DAD were 0.929 and 0.932 for the inter-examiner and test-retest evaluations respectively. The reliability indexes were also high (Kappa 0.72 p<0.001 inter-examiners and 0.85 p<0.001 test-retest). The Brazilian version of DAD was easy to administer and had good reliability to assess the functional status of demented patients. It will contribute to the follow-up of these patients in our population. Moreover, it can be used in transcultural studies on functional abilities in dementia.

Carthery-Goulart MT, Areza-Fegyveres R, Schultz RR, Okamoto I, Caramelli P, Bertolucci PH, Nitrini R. · Clínica Neurológica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #17952308 links to  free full text

Abstract: OBJECTIVE: Translating and adapting the Cornell scale for depression in dementia to the Portuguese language and verifying the interrater and test-retest reliability of the translated and adapted version. METHOD: The Cornell scale was translated into Portuguese and back translated into English. Divergences of translation were identified and discussed, resulting in a version which was submitted to a pre-test for cross-cultural adaptation. The final version was administered to a sample of 29 patients with probable AD and to their caregivers. RESULTS: The Cornell Scale presented good interrater (Kappa=0,77; p<0,001) and test-retest reliability (Kappa=0,76; p<0,001). The final version was easy to administer and well understood by the caregivers. CONCLUSION: The Brazilian version of the Cornell Scale is an instrument with good reliability to evaluate depression in patients with dementia. This tool will contribute to the evaluation and follow-up of depressed patients with dementia in our population and may also be used in multicentric studies with Brazilian population.

Areza-Fegyveres R, Rosemberg S, Castro RM, Porto CS, Bahia VS, Caramelli P, Nitrini R. · Behavioral and Cognitive Neurology Unit, Department of Neurology, School of Medicine, University of São Paulo, Rua Oscar Freire 1702/44, 05409-011 São Paulo, SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #17952290 links to  free full text

Abstract: A 61-year-old ex-boxer presented with a three-year history of progressive memory decline. During a seven-year follow-up period, there was a continuous cognitive decline, very similar to that usually observed in Alzheimer's disease. Parkinsonian, pyramidal or cerebellar signs were conspicuously absent. Neuropathological examination revealed the typical features of dementia pugilistica: cavum septi pellucidi with multiple fenestrations, numerous neurofibrillary tangles in the cerebral isocortex and hippocampus (and rare senile plaques). Immunohistochemistry disclosed a high number of tau protein deposits and scarce beta-amyloid staining. This case shows that dementia pugilistica may present with clinical features practically undistinguishable from Alzheimer's disease.

Raicher I, Shimizu MM, Takahashi DY, Nitrini R, Caramelli P. · Behavioral and Cognitive Neurology Unit, University of São Paulo School of Medicine, São Paulo, Brazil. · Int Psychogeriatr. · Pubmed #17822571 No free full text.

Abstract: BACKGROUND: There is little, though growing, interest in the research area of attitudes held among physicians towards disclosing the diagnosis of dementia and Alzheimer's disease (AD), or the current practice on AD disclosure. This study aimed to investigate the practice and attitudes of specialized physicians towards AD diagnosis disclosure in Brazil. METHODS: A questionnaire was devised to survey the current practice and attitudes regarding diagnosis disclosure of AD in Brazil and sent to specialized physicians (170 geriatricians, 300 neurologists and 500 psychiatrists) by electronic mail. RESULTS: From 970 potential respondents, 181 physicians who usually attend AD patients returned the questionnaire. There were no significant differences between the three specialties regarding the frequency with which they informed patients of their AD diagnosis (p = 0.17). The results revealed that only 44.8% of the physicians would regularly inform the patient of the diagnosis, although 85.6% of these use clear terminology. Despite their usual practice, 76.8% would want to know their diagnosis if they themselves were affected by AD. CONCLUSIONS: Disclosure of AD diagnosis is not common among specialized physicians in Brazil and different factors are involved. In the clinical context, discussion on advantages of diagnosis disclosure can be useful for improving the care of AD patients and their families.

Serrano CM, Allegri RF, Caramelli P, Taragano FE, Camera L. · LLaboratorio de Investigación de la Memoria del Hospital A. Zubizarreta (GCBA), Buenos Aires, Argentina. 2 · Medicina (B Aires). · Pubmed #17408016 No free full text.

Abstract: Mild cognitive impairment (MCI) refers to persons who are slightly cognitively impaired for age but do not meet the criteria for dementia. MCI has been related to a pre-dementia stage of Alzheimer's disease (AD). However, other possible diagnoses such as cerebro-vascular disease, frontotemporal dementia or normal aging have been considered. Diagnosis, etiology and conversion to dementia are a source of ambiguity in MCI. The aim was to evaluate the opinion of experts on dementia and of general practitioners concerning MCI. A total of 24 experts from Argentina and Brazil (16 neurologists and 8 psychiatrists) and 30 general practitioners agreed to reply to a questionnaire on MCI (adapted from Dubois inventory, 2003). Of these, 92% of experts considered MCI as an ambiguous entity, not necessarily as a "pre-dementia" stage; 63% confirmed a tendency to worsen over the time and 83% of experts decided to initiate treatment using cholinesterase inhibitors, memantine and vitamin E. The opinion on MCI was that a priori it is not only an Alzheimer disease pre-dementia stage, but most of them consider the treatment against AD. MCI is a heterogeneous entity that should be classified as an open category and making it necessary to standardize definitions and design diagnosis guides to better understand Alzheimer disease pre-dementia stage.

de Souza JN, Chaves EC, Caramelli P. · College of Nursing, University of São Paulo. · Rev Lat Am Enfermagem. · Pubmed #17375238 links to  free full text

Abstract: The intensity of stress experiences and elaboration of coping essentially depend on individuals' cognitive assessment. Considering the cognitive impairment of elderly persons with Alzheimer's disease (DA), this study aimed to identify their coping style. The Jalowiec Coping Inventory was applied to 60 elderly, 30 in the control group and 30 in the DA group. The results demonstrated a predominance of emotion-focused coping in the DA group and problem-focused coping in the control group, but the difference was not statistically significant (p=0.124). In addition, it was observed that individuals with better cognitive development in the DA group selected problem-focused coping strategies (p=0.0074). Thus, it seems there is a tendency to select evasive and emotional control strategies in demented elderly with worsened cognitive performance, rather than attempting to solve the problem or minimize its consequences.

Caramelli P, Carthery-Goulart MT, Porto CS, Charchat-Fichman H, Nitrini R. · Behavioral and Cognitive Neurology Unit, Department of Neurology, University of São Paulo School of Medicine, São Paulo, Brazil. · Alzheimer Dis Assoc Disord. · Pubmed #17334275 No free full text.

Abstract: Brief cognitive tests are widely used for dementia screening, but are usually influenced by education. The present work aimed to determine education-adjusted cut-off scores and correspondent sensitivity (S) and specificity (Sp) values of the category fluency (CF) test (animals/min) as a screening tool for Alzheimer disease (AD). Eighty-eight patients with mild AD and 117 normal matched controls were evaluated. Patients and controls were divided into 4 groups according to educational level (illiterates, 1 to 3, 4 to 7, and > or =8 y) and were administered the CF test. In each group, cut-off values were determined using Receiver Operator Characteristic analysis. The areas under Receiver Operator Characteristic curves were 0.922/0.914/0.963/0.954, for the identification of AD among the groups of illiterates, 1 to 3, 4 to 7, and > or =8 years of education, respectively. The cut-off points for each group were 9 (S=90.5% and Sp=80.6%) for illiterates; 12 (S=95.2%% and Sp=80.0%) for 1 to 3 years; 12 (S=91.3% and Sp=91.9%) for 4 to 7 years, and 13 for those with > or =8 years (S=82.6% and Sp=100.0%). These results suggest that the CF may be a useful screening test for mild AD in different educational levels, with the need of using specific cut-off scores adjusted for each range of schooling.

Vilela LP, Caramelli P. · Departamento de Neurologia, Faculdade de Medicina, Universidade de São Paulo, Rua Itapeva 518, 01332-000 São Paulo/SP. · Rev Assoc Med Bras. · Pubmed #16847520 links to  free full text

Abstract: BACKGROUND: There are several ethical aspects related to the medical assistance of patients with Alzheimer's disease (AD) including diagnostic disclosure to the patient, performance of autopsy for diagnostic confirmation, and also topics pertaining to the caregivers constantly subjected by these patients to physical and mental stress. This work investigates some of these issues, by comparing family caregivers of patients with AD followed-up at both public and private health services. METHODS: Twenty family caregivers of AD patients followed up at a public university hospital and 20 family caregivers of AD patients followed up at a private clinic were interviewed using a specific questionnaire comprised of 36 questions about diagnosis, treatment and prognosis of the disease. RESULTS: The two groups presented similar age and gender distributions while the socioeconomic level was higher for the private clinic group. No differences were found between opinions of both groups regarding diagnostic disclosure to the patients, with 42.5% of the total in favor of disclosing the information only to the family. The number of caregivers who agreed with performance of autopsy was significantly higher in the public service (35% against 30% in the private clinic). Twenty caregivers (50% of the total sample) spontaneously manifested the wish to allow an autopsy for research purposes. CONCLUSION: Disclosure of AD diagnosis to patients was approved by more than half of all family caregivers and these rates were not correlated to the socioeconomic level. This variable, however, influenced the concordance rate related to the post-mortem neuropathological examination.

Novelli MM, Dal Rovere HH, Nitrini R, Caramelli P. · Grupo de Neurologia Cognitiva e do Comportamento da Divisião de Clínica Neurológica do Hospital das Clínicas (HC) da Faculdade de Medicina da Universidade de São Paulo (FMUSP) São Paulo, SP, Brasil. · Arq Neuropsiquiatr. · Pubmed #16100962 No free full text.

Abstract: OBJECTIVE: To present the internal validation of the quality of life (QOL) evaluation scale for patients with Alzheimer's disease (AD) and their caregivers/family members, proposed by Logsdon et al. METHOD: The scale was adapted through translation, back translation and equivalence evaluation. The Portuguese version was administered to a sample of 40 patients with mild to moderate AD according to NINCDS ADRDA and DSM-III-R criteria, and also to their respective caregivers/family members. RESULTS: The reliability of the instrument was excellent, both in the intra and the inter-examiner test-retest. The correlation coefficients for the intra-examiner assessment were 0.87/0.95/0.95 (p < 0.001)) for the patient, family and caregiver versions, respectively. The correlation coefficients for the inter-examiner assessment were 0.76/0.96/0.93 (p < 0.001) for the patients, family and caregiver versions, respectively. The reliability was excellent for both the patient and the relatives' versions in relation to the patient's QOL (alpha = 0.81 and 0.85, respectively), and also in relation to the caregiver's QOL (alpha = 0.84). CONCLUSION: The adapted version of the instrument proved to be straightforward and brief, presenting excellent stability and reliability. The Portuguese version can be obtained by contacting the first author.

Nitrini R, Caramelli P, Herrera E, de Castro I, Bahia VS, Anghinah R, Caixeta LF, Radanovic M, Charchat-Fichman H, Porto CS, Teresa Carthery M, Hartmann AP, Huang N, Smid J, Lima EP, Takahashi DY, Takada LT. · Behavioral and Cognitive Neurology Unit, Department of Neurology, University of São Paulo School of Medicine, Brazil. · Int J Geriatr Psychiatry. · Pubmed #15717343 No free full text.

Abstract: BACKGROUND: The influence of dementia on mortality has not yet been reported for a Latin American country. OBJECTIVES: To evaluate the influence of dementia on mortality of a community-dwelling elderly population in Brazil, and to verify the extent to which the diagnosis of dementia is reported on death certificates. METHODS: A cohort of 1,656 individuals, aged 65 and over, was screened for dementia at their domiciles, in 1997. The same population was re-evaluated in 2000, and information on deaths was obtained from relatives and from the municipal obituary service. Kaplan-Meier curves were used for the survival analysis, and the mortality risk ratio (MMR) was calculated using Cox proportional hazards models. RESULTS: We obtained data from 1,393 subjects, corresponding to 84.1% of the target population. The number of deaths was 58 (51.3%) among the patients with dementia and 163 (12.7%) among those without dementia in 1997 (p <0.0001). Dementia and Alzheimer's disease (AD) decreased survival, with hazards ratios of 5.16 [95% Confidence Interval (CI): 3.74-7.12] for dementia and 4.76 (95% CI: 3.16-7.18) for AD. The Cox proportional hazards model identified dementia (MMR=3.92, 95% CI: 2.80-5.48) as the most significant predictor of death, followed by age, history of stroke, complaints of visual impairment and heart failure and by severe arterial hypertension in the baseline evaluation. Dementia and/or AD were mentioned in only 12.5% of the death certificates of individuals with dementia. CONCLUSIONS: Dementia causes a significant decrease in survival, and the diagnosis of dementia is rarely reported on death certificates in Brazil.

Nitrini R, Caramelli P, Herrera E, Bahia VS, Caixeta LF, Radanovic M, Anghinah R, Charchat-Fichman H, Porto CS, Carthery MT, Hartmann AP, Huang N, Smid J, Lima EP, Takada LT, Takahashi DY. · Behavioral and Cognitive Neurology Unit, Department of Neurology, University of São Paulo School of Medicine, São Paulo, Brazil. · Alzheimer Dis Assoc Disord. · Pubmed #15592138 No free full text.

Abstract: The authors report the incidence of dementia in a community-dwelling Brazilian population. In 1997, 1656 individuals aged 65 years or more, the majority being of very low educational level, were screened at their homes in Catanduva, Brazil, and dementia was diagnosed in 118 cases. The remaining 1538 individuals were rescreened 3.25 years later applying a health questionnaire, the Mini-Mental State Examination (MMSE) and the Pfeffer Functional Activities Questionnaire (PFAQ). According to 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. A total of 1119 individuals were rescreened and 50 incident cases of dementia (28 with Alzheimer disease [AD]) were identified. The incidence rate of dementia was 13.8 and of AD was 7.7 per 1000 person-years for individuals aged 65 years or older. The incidence rates of dementia almost doubled with every 5 years of age. There was no difference according to gender, but women had a higher incidence of dementia, predominantly AD, in very old age. There was a trend for higher incidence of dementia in illiterates (p = 0.07), but multivariate analysis disclosed significant association only between age and higher incidence of dementia. The incidence rates of dementia in this Brazilian community are comparable to those reported in Western and Asian studies.

Hartmann AP, Almeida SM, Livramento JA, Nitrini R, Takahashi D, Caramelli P. · Department of Neurology, University of São Paulo School of Medicine, São Paulo SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #15476062 links to  free full text

Abstract: Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and tau-associated neurofibrillary tangles in the cerebral tissue. The search for antemortem biomarkers is intense including analysis of cerebrospinal fluid (CSF) beta-amyloid and tau proteins concentrations seeking for an accurate and early diagnosis. Levels of hyperphosphorylated tau at threonine 181 were measured in the CSF of 34 patients with AD (19 with senile AD - SAD and eight with presenile AD - PSAD) and seven with other dementias (OD). The levels of CSF phosphotau were significantly higher in the AD patients compared to OD (AUC 0.812), with no association with severity of dementia, age of onset, duration of the disease or scores in the Mini-Mental State Examination. There were no differences of phosphotau levels between SAD and PSAD patients. These findings corroborate some previous studies and indicate that CSF phosphotau may help to differentiate AD from other dementias.

Takada LT, Caramelli P, Radanovic M, Anghinah R, Hartmann AP, Guariglia CC, Bahia VS, Nitrini R. · Behavioral and Cognitive Neurology Unit, Department of Neurology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #14762592 links to  free full text

Abstract: The importance of investigating the etiology for dementia lies in the possibility of treating potentially reversible dementias. The aims of this retrospective study are to determine the prevalence of potentially reversible dementias among 454 outpatients seen at the Cognitive and Behavioral Neurology Unit, Hospital das Clínicas, São Paulo University School of Medicine-Brazil, between the years of 1991 and 2001, and observe their evolution in follow-up. Among the initial 454 patients, 275 fulfilled the DSM-IV criteria for dementia. Alzheimer's disease was the most frequent diagnosis (164 cases; 59.6%). Twenty-two cases (8.0%) of potentially reversible dementia were observed, the most frequent diagnoses being neurosyphilis (nine cases) and hydrocephalus (six cases). Full recovery was observed in two patients and partial recovery in 10 patients. Two cases were not treated and eight cases were lost on follow-up. The prevalence found in the present study falls within the range reported in previous studies (0-30%).

Porto CS, Fichman HC, Caramelli P, Bahia VS, Nitrini R. · Behavioral and Cognitive Neurology Unit, Department of Neurology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #12894264 links to  free full text

Abstract: OBJECTIVES: To verify the diagnostic accuracy of the Brazilian version of the Mattis Dementia Rating Scale (DRS) in the diagnosis of patients with mild dementia in Alzheimer's disease (AD); to verify the interference of the variables age and schooling on the performance of the DRS. METHOD: The DRS was administered to 41 patients with mild AD and to 60 controls. In order to analyze the effects of age and schooling on the performance of the tests, patients and controls were separated into three age groups and three levels of schooling. RESULTS: The cutoff score of 122 showed a sensitivity of 91.7 % and specificity of 87.8 %. Age and schooling interfered in the DRS total score and in the scores of its subscales. CONCLUSION: The DRS showed good diagnostic accuracy in the discrimination of patients with mild AD from the control individuals. In the sample examined, the effects of schooling were more marked than age.