Marcia Radanovic

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 Alzheimers 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 (0.25-0.5 mmol/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 (Aβ(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 Alzheimers 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 Alzheimers disease.

CAMcog as a screening tool for diagnosis of mild cognitive impairment and dementia in a Brazilian clinical sample of moderate to high education

The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut‐off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut‐off values are also necessary, taking into account cultural and educational effects.

Mild cognitive impairment: cognitive screening or neuropsychological assessment?

OBJECTIVE To describe the neuropsychological profile of mild cognitive impairment subtypes (amnestic, non-amnestic and multiple-domain) of a clinical sample. We further address the diagnostic properties of the Mini-Mental State Examination and the Cambridge Cognitive Examination for the identification of the different mild cognitive impairment subtypes in clinical practice. METHOD Cross-sectional clinical and neuropsychological evaluation of 249 elderly patients attending a memory clinic at a university hospital in Sao Paulo, Brazil. RESULTS The performance of patients with mild cognitive impairment was heterogeneous across the different subtests of the neuropsychological battery, with a trend towards an overall worse performance for amnestic (particularly multiple domain) mild cognitive impairment as compared to non-amnestic subtypes. Screening tests for dementia (Mini-Mental State Examination and Cambridge Cognitive Examination) adequately discriminated cases of mild Alzheimers disease from controls, but they were not accurate to discriminate patients with mild cognitive impairment (all subtypes) from control subjects. CONCLUSIONS The discrimination of mild cognitive impairment subtypes was possible only with the aid of a comprehensive neuropsychological assessment. It is necessary to develop new strategies for mild cognitive impairment screening in clinical practice.

Normative data for the Brazilian population in the Boston Diagnostic Aphasia Examination: influence of schooling

In Neurolinguistics, the use of diagnostic tests developed in other countries can create difficulties in the interpretation of results due to cultural, demographic and linguistic differences. In a country such as Brazil, with great social contrasts, schooling exerts a powerful influence on the abilities of normal individuals. The objective of the present study was to identify the influence of schooling on the performance of normal Brazilian individuals in the Boston Diagnostic Aphasia Examination (BDAE), in order to obtain reference values for the Brazilian population. We studied 107 normal subjects ranging in age from 15 to 84 years (mean +/- SD = 47.2 +/- 17.6 years), with educational level ranging from 1 to 24 years (9.9 +/- 4.8 years). Subjects were compared for scores obtained in the 28 subtests of the BDAE after being divided into groups according to age (15 to 30, N = 24, 31 to 50, N = 33 and 51 years or more, N = 50) and education (1 to 4, N = 26, 5 to 8, N = 17 and 9 years or more, N = 61). Subjects with 4 years or less of education performed poorer in Word Discrimination, Visual Confrontation Naming, Reading of Sentences and Paragraphs, and Primer-Level Dictation (P < 0.05). When breakdown by schooling was 8 years or less, subjects performed poorer in all subtests (P < 0.05), except Responsive Naming, Word Recognition and Word-Picture Matching. The elderly performed poorer (P < 0.05) in Complex Ideational Material, Visual Confrontation Naming, Comprehension of Oral Spelling, Written Confrontation Naming, and Sentences to Dictation. We present the reference values for the cut-off scores according to educational level.

Performance of a Brazilian population on the test of functional health literacy in adults

OBJECTIVE To analyze the scoring obtained by an instrument, which evaluates the ability to read and understand items in the health care setting, according to education and age. METHODS The short version of the Test of Functional Health Literacy in Adults was administered to 312 healthy participants of different ages and years of schooling. The study was conducted between 2006 and 2007, in the city of São Paulo, Southeastern Brazil. The test includes actual materials such as pill bottles and appointment slips and measures reading comprehension, assessing the ability to read and correctly pronounce a list of words and understand both prose passages and numerical information. Pearson partial correlations and a multiple regression model were used to verify the association between its scores and education and age. RESULTS The mean age of the sample was 47.3 years(sd=16.8) and the mean education was 9.7 years(sd=5; range: 1 - 17). A total of 32.4% of the sample showed literacy/numeracy deficits, scoring in the inadequate and marginal functional health literacy ranges. Among the elderly (65 years or older) this rate increased to 51.6%. There was a positive correlation between schooling and scores (r=0.74; p<0.01) and a negative correlation between age and the scores (r=-0.259; p<0.01). The correlation between the scores and age was not significant when the effects of education were held constant (rp=-0.031, p=0.584). A significant association (B=3.877, Beta =0.733; p<0.001) was found between schooling and scores. Age was not a significant predictor in this model (B=-0.035, Beta=-0.22; p=0.584). CONCLUSIONS The short version of the Test of Functional Health Literacy in Adults was a suitable tool to assess health literacy in the study population. The high number of individuals classified as functional illiterates in this test highlights the importance of special assistance to help them properly understand directions for healthcare.OBJETIVO: Analisar os escores de instrumento que avalia habilidade de leitura e compreensao de materiais da area da saude segundo escolaridade e idade. METODOS: Foram avaliados 312 participantes saudaveis de diferentes idades por meio da versao reduzida do instrumento Test of Functional Health Literacy in Adults. O estudo foi realizado entre 2006 e 2007 na cidade de Sao Paulo (SP). O instrumento envolve materiais como frascos de medicamentos e cartoes de agendamento de consultas, avaliando a compreensao de leitura e de conceitos numericos. Os testes de correlacao parcial e de Pearson e um modelo de regressao multipla foram usados para verificar a associacao entre os escores no instrumento, escolaridade e idade. RESULTADOS: As medias de idade e de escolaridade da amostra foram respectivamente 47,3 (dp=16,8 ) e 9,7 (dp=5; de um a 17 anos de estudo). O total de 32,4% da amostra mostraram deficits de alfabetizacao funcional/ uso de conceitos numericos na area de saude, com desempenho inadequado ou limitrofe no instrumento. Entre idosos (65 anos ou mais) esta taxa atingiu 51,6%. Encontrou-se correlacao positiva entre anos de estudo e escores no instrumento (r=0,740; p<0,01) e correlacao negativa entre idade e escores no instrumento (r=-0,259; p<0,01). A correlacao entre escores no instrumento e idade nao foi significante quando os efeitos da escolaridade foram controlados (r=-0,031, p=0,584). Uma associacao significante (B=3,877, Beta=0,733; p<0,001) foi encontrada entre anos de estudo e escores no instrumento. A idade nao foi uma variavel preditiva no modelo (B=-0,035, Beta=-0,22; p=0,584). CONCLUSOES: O instrumento e adequado para avaliar a alfabetizacao funcional em saude na populacao brasileira. O elevado numero de individuos classificados como analfabetos funcionais indica a importância de adocao de medidas especiais para ajudar estes individuos a compreenderem corretamente as orientacoes para cuidados de saude.

Boston naming test: performance of Brazilian population from São Paulo

BACKGROUND The Boston Naming Test is frequently used to evaluate naming deficits. The scores used in Brazil have been the same as those used in the American version. In the case of individuals with poor schooling associated to cerebral lesions, a frequent situation in our country, one runs the risk of considering a poor performance as a deficit, what in fact is a consequence of lack of knowledge and cultural deprivation. AIM to evaluate the influence of age and schooling in the naming ability of normal individuals, from São Paulo city, in a visual confrontation task. METHOD 133 normal volunteers, aged between 28 and 70 years. RESULTS the scores obtained in spontaneous naming were [mean (SD)]: [39.4 (9.8)]; per age group: 28 - 50 years [39.5 (10.5)], 51 - 70 years [39.1 (9.1)]; per schooling: 1 - 4 years [33.7 (9.6)], 5 - 8 years [36.6 (7.9)], 9 or more [47.4 (6)]. The comparison between the performances of the two age groups did not reveal any significant differences. Higher educational level determined a better performance both in spontaneous and facilitated naming. Cues of stimuli were necessary for the individuals to access the correct name, especially for the group with lower educational level. Phonemic cues, on the other hand, benefited individuals with more than eight years of formal education. The suggested cut-off score for the test to be use in Brazil was calculated by the ROC curve analysis and based on the comparison between normal and aphasic individuals. CONCLUSION schooling was the variable that had the greatest influence on performance. Although the level of difficulty of a few items may, to some extent, differ between English and Portuguese, the translated version of the BNT can be used without any adaptations for the Brazilian population, provided that the level of education is taken in consideration when interpreting the results.

Profiles of functional deficits in mild cognitive impairment and dementia: benefits from objective measurement.

The magnitude of functional impairment that may indicate the threshold between MCI and incipient Alzheimers disease (AD) has not been clearly defined. The objective was to examine the pattern of functional impairment in the continuum MCI-AD. Eighty-nine older adults (32 cognitively unimpaired, 31 MCI, and 26 AD patients) were examined with the Brazilian version of the Direct Assessment of Functional Status (DAFS-BR) at a university-based memory clinic. MCI patients were sub-divided according to the progression to AD upon follow-up, and had baseline cognitive, functional and biological variables analyzed. MCI patients displayed mild deficits in functional abilities, with intermediate scores as compared to controls and AD. The DAFS-BR items that differentiated MCI from controls involved the ability to deal with finances and shopping skills. At baseline, scores obtained by MCI patients who converted to AD were not significantly different from scores of nonconverters. The magnitude of functional deficits was associated with AD-like pathological findings in the CSF. In conclusion, MCI patients present with early functional changes in complex, instrumental abilities that require the integrity of memory and executive functions. The objective measurement of the functional state may help identify older adults with increased risk of developing dementia in the MCI-AD continuum.

Speech and language disturbances due to subcortical lesions

Over the last few decades, the number of studies concerning the role of subcortical structures in cognition has increased due to advances in neuroimaging. We describe the language and speech disturbances found in 16 patients with subcortical lesions (9 in basal ganglia and 7 in thalamus), evaluated by CT scan, MRI, and SPECT. Language assessment included the Boston Diagnostic Aphasia Examination, Boston Naming Test, and Token Test. Motor-articulatory alterations predominated in the non-thalamic group; in the thalamic group, there was a higher frequency of language alterations, especially in naming and auditory comprehension; verbal memory and attentional impairments may have contributed to this. We also found hypoperfusion in cortical language areas, and therefore participation of cortical dysfunction cannot be ruled out.

Thalamus and language: interface with attention, memory and executive functions

Subcortical structures are in a strategic functional position within the cognitive networks. Their lesion can interfere with a great number of functions. We studied six patients with thalamic vascular lesions (three left sided, two right sided and one bilateral), to characterize their repercussion in the communicative abilities and the interface between language alterations and other cognitive abilities, as attention, memory and frontal executive. All patients were evaluated through a functional interview (discourse analysis), and the following batteries: Boston Diagnostic Aphasia Examination, Boston Naming Test, Token Test, Benton Visual Retention Test, Trail Making, Wisconsin Card Sorting and frontal scripts. All patients performed MRI and five underwent SPECT. Results show that these patients present impairment in several cognitive domains, especially attention and executive functions (working memory, planning and self-monitoring); those with right lesions have an additional visuospatial impairment. Such alterations interfere with language abilities, and this fact must be considered in the rehabilitation efforts.

Prevalence of potentially reversible dementias in a dementia outpatient clinic of a tertiary university-affiliated hospital in Brazil

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. Alzheimers 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%).