Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer`s disease, although no benefits were obtained from short-term treatment. Aims To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5mmol/l) (n=24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (A beta(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392. Results Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P=0.03) and better perform-ance on the cognitive subscale of the Alzheimer`s Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer`s disease.

Use of the frontal assessment battery in evaluating executive dysfunction in patients with Huntington`s disease

The frontal assessment battery (FAB) is a bedside cognitive scale designed to measure executive functions. Huntington`s disease (HD) is a neurodegenerative disorder characterized by motor, behavioral, and cognitive dysfunction. The aim of this study was to check the validity of the FAB for the evaluation of cognitive impairment in patients with HD. Forty-one patients diagnosed with HD and 53 healthy controls matched by education, sex and age were evaluated with a validated Brazilian version of the UHDRS, the VFT, the SDMT, the SIT, the MMSE, and the FAB. The diagnosis of HD was made by DNA analysis. FAB scores were lower in patients than in the controls (p < 0.001) and had significant correlations with the VFT (r = 0.79; p < 0.05), the SDMT (r = 0.80; p < 0.05), the SIT (r = 0.72; p < 0.05), the MMSE (r = 0.83; p < 0.05), the FCS (r = 0.79; p < 0.05) and the motor section of the UHDRS (r = -0.80; p < 0.05). The FAB differentiated between HD patients in the initial and later stages of the disease. The one-year longitudinal evaluation revealed a global trend toward a worsening in the second score of the FAB. The results demonstrate that the FAB presents good internal consistency and also convergent and discriminative validity; therefore it is a useful scale to assess executive functions and to evaluate cognitive impairment in patients with HD.

Validation of the Brazilian version of the quality of life scale for patients with Alzheimer`s disease and their caregivers (QOL-AD)

Quality of life (QOL) has been extensively studied in clinical trials and in research on chronic degenerative diseases and dementia. The aim of this study was to assess the reliability and construct validity of the Brazilian version of the QOL scale in Alzheimer`s disease (AD; QOL-AD). The QOL-AD was administered to 60 patients with mild or moderate AD and to their caregivers. The construct validation was accomplished through correlations amongst total scores of patients` and caregivers` reports on patients` quality of life (PQOL and C-PQOL, respectively), and data related to cognitive impairment, depressive symptoms, functional performance, behavioral disturbances and a generic instrument of quality of life (WHOQOL-brief), as well as correlation of total score of caregivers` reports on their own quality of life (CQOL) with the measurements cited above, QOL-AD patient reports, and depressive symptoms. The reliability was high for PQOL, C-PQOL, and CQOL versions (Cronbach`s alpha = 0.80, 0.83, and 0.86, respectively). We observed significant correlations in the construct validity of all three versions regarding the variables associated with the disease and also with WHOQOL-brief. The scale took, on average, six min for each version. The results indicate reliability and construct validity of the Brazilian version of the QOL-AD in the studied sample.

Alzheimer`s disease diagnosis disclosure in Brazil: a survey of specialized physicians` current practice and attitudes

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.

The Genetics of Alzheimer`s Disease in Brazil: 10 Years of Analysis in a Unique Population

Alzheimer`s Disease (AD) is the most common type of dementia among the elderly, with devastating consequences for the patient, their relatives, and caregivers. More than 300 genetic polymorphisms have been involved with AD, demonstrating that this condition is polygenic and with a complex pattern of inheritance. This paper aims to report and compare the results of AD genetics studies in case-control and familial analysis performed in Brazil since our first publication, 10 years ago. They include the following genes/markers: Apolipoprotein E (APOE), 5-hidroxytryptamine transporter length polymorphic region (5-HTTLPR), brain-derived neurotrophin factor (BDNF), monoamine oxidase A (MAO-A), and two simple-sequence tandem repeat polymorphisms (DXS1047 and D10S1423). Previously unpublished data of the interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) genes are reported here briefly. Results from others Brazilian studies with AD patients are also reported at this short review. Four local families studied with various markers at the chromosome 21, 19, 14, and 1 are briefly reported for the first time. The importance of studying DNA samples from Brazil is highlighted because of the uniqueness of its population, which presents both intense ethnical miscegenation, mainly at the east coast, but also clusters with high inbreeding rates in rural areas at the countryside. We discuss the current stage of extending these studies using high-throughput methods of large-scale genotyping, such as single nucleotide polymorphism microarrays, associated with bioinformatics tools that allow the analysis of such extensive number of genetics variables, with different levels of penetrance. There is still a long way between the huge amount of data gathered so far and the actual application toward the full understanding of AD, but the final goal is to develop precise tools for diagnosis and prognosis, creating new strategies for better treatments based on genetic profile.

Apolipoprotein E genotype is related to nitric oxide production in platelets

The presence of the, 4 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 epsilon 4 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. Copyright (C) 2008 John Wiley & Sons, Ltd.

The Prospective and Retrospective Memory Questionnaire: A population-based random sampling study

The Prospective and Retrospective Memory Questionnaire (PRMQ) has been shown to have acceptable reliability and factorial, predictive, and concurrent validity. However, the PRMQ has never been administered to a probability sample survey representative of all ages in adulthood, nor have previous studies controlled for factors that are known to influence metamemory, such as affective status. Here, the PRMQ was applied in a survey adopting a probabilistic three-stage cluster sample representative of the population of Sao Paulo, Brazil, according to gender, age (20-80 years), and economic status (n=1042). After excluding participants who had conditions that impair memory (depression, anxiety, used psychotropics, and/or had neurological/psychiatric disorders), in the remaining 664 individuals we (a) used confirmatory factor analyses to test competing models of the latent structure of the PRMQ, and (b) studied effects of gender, age, schooling, and economic status on prospective and retrospective memory complaints. The model with the best fit confirmed the same tripartite structure (general memory factor and two orthogonal prospective and retrospective memory factors) previously reported. Women complained more of general memory slips, especially those in the first 5 years after menopause, and there were more complaints of prospective than retrospective memory, except in participants with lower family income.

Influence of education and depressive symptoms on cognitive function in the elderly

Objective: The purpose of the present study was to investigate the influence that education and depression have on the performance of elderly people in neuropsychological tests. Methods: The study was conducted at the Institute of Psychiatry, University of Sao Paulo School of Medicine, Hospital das Clinicas. All of the individuals evaluated were aged 60 or older. The study sample consisted of 59 outpatients with depressive disorders and 51 healthy controls. We stratified the sample by level of education: low = 1-4 years of schooling; high = 5 or more years of schooling. Evaluations consisted of psychiatric assessment, cognitive assessment, laboratory tests and cerebral magnetic resonance imaging. Results: We found that level of education influenced all the measures of cognitive domains investigated (intellectual efficiency, processing speed, attention, executive function and memory) except the Digit Span Forward and Fuld Object Memory Evaluation (immediate and delayed recall), whereas depressive symptoms influenced some measures of memory, attention, executive function and processing speed. Although the combination of a low level of education and depression had a significant negative influence on Stroop Test part B, Trail Making Test part B and Logical Memory (immediate recall), we found no other significant effects of the interaction between level of education and depression. Conclusion: The results of this study underscore the importance of considering the level of education in the analysis of cognitive performance in depressed elderly patients, as well as the relevance of developing new cognitive function tests in which level of education has a reduced impact on the results.