Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment

Objectives: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. Methods: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. Results: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively. Conclusion: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.

Decision tree-based classification as a support to diagnosis in the Alzheimer's disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis

Objective: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. Methods: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aβ1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. Results: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. Conclusion: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.

Early diagnosis and treatment of Alzheimers disease: new definitions and challenges

The prevalence of Alzheimer's disease (AD), a progressive neurodegenerative disorder, is expected to more than double by 2050. Studies on the pathophysiology of AD have been changing our understanding of this disorder and setting a new scenario for drug development and other therapies. Concepts like the "amyloid cascade" and the "continuum of AD," discussed in this article, are now well established. From updated classifications and recommendations to advances in biomarkers of AD, we aim to critically assess the literature on AD, addressing new definitions and challenges that emerged from recent studies on the subject. Updates on the status of major clinical trials are also given, and future perspectives are discussed.

Assessing treatment response to prophylactic lithium use in patients with bipolar disorder / Avaliação da resposta terapêutica ao tratamento de manutenção com lítio em pacientes com transtorno afetivo bipolar

ABSTRACT Objetive To identify potential clinical and epidemiological predictors of long-term response to lithium treatment. Methods A total of 40 adult outpatients followed in an university hospital, with confirmed diagnosis of bipolar disorder and with history of lithium use for at least a six months period, had their response to this medication assessed through the use of a standardized instrument. The ALDA scale is based on retrospective clinical data, in our study assessed through a thoroughly reviewed of the medical charts, and is used to evaluate the clinical improvement with the treatment (Criterion A), corrected by the acknowledgement of possible confounding factors, such as duration of the treatment, compliance and concomitant use of additional medications (Criterion B), in order to estimate the response that can be specifically attributable to lithium. Results Our study found an inverse relation between the number of mood episodes with psychotic symptoms and lithium treatment outcome. Conclusion The results reinforce the hypothesis that lithium seems to be less efficacious in patients with bipolar disorder who present psychotic symptoms.

RESUMO Objetivo Identificar potenciais preditores clínicos e epidemiológicos de resposta terapêutica ao uso prolongado de lítio. Métodos Um total de 40 pacientes adultos em tratamento ambulatorial em um hospital universitário, com diagnóstico confirmado de transtorno afetivo bipolar e história de pelo menos seis meses de uso de lítio, teve sua resposta a essa medicação avaliada com a utilização de um instrumento padronizado. A escala ALDA leva em consideração informações clínicas obtidas de forma retrospectiva, em nosso estudo, por meio de minuciosa revisão dos prontuários médicos, para julgar a melhora clínica obtida com o tratamento (Critério A), corrigida pela identificação de possíveis fatores confundidores, tais como duração do tratamento, adesão e uso concomitante de outras drogas (Critério B), de forma a estimar a resposta que pode ser atribuída especificamente ao uso do lítio. Resultados Nosso estudo encontrou uma relação inversa entre o número de episódios de humor com a presença de sintomas psicóticos e o desfecho no tratamento com lítio. Conclusão Esses resultados reforçam a hipótese de que o lítio parece ser menos eficaz em pacientes com transtorno afetivo bipolar que manifestam sintomas psicóticos.

Psychosis associated with methimazole-induced hypothyroidism: a case report / Psicose associada com hipotireoidismo induzido por metimazol: um relato de caso

INTRODUCTION: Thyroid dysfunction has often been associated with several psychiatric manifestations. Previous case reports/series suggest the possible role played by acute alteration of thyroid status in the onset of psychotic symptoms. METHODS: Case report and literature review. RESULTS: A 45-year-old woman with no psychiatric antecedents was brought to the ER with a full-blown psychotic episode, marked by paranoid delusions, which developed gradually over two months. She had been treated elsewhere for hyperthyroidism for five years with methimazole 40 mg/d, with poor compliance. One month before the beginning of the psychotic symptoms, methimazole was raised to 60 mg/d and she started taking it correctly. Five months earlier she had TSH: 0.074 uUI/ml and free T4: 1.3 ng/dl. At admission we found a diffuse thyroid goiter, TSH: 70.9 uUI/ml and free T4: 0.03 ng/dl. Brain CT was normal. We hospitalized her with the diagnosis of a psychosis secondary to hypothyroidism, suspended methimazole, and gave her levothyroxine (up to 75 µg/d) and risperidone (2 mg/d). The patient had a quick remission and was discharged after 15 days. Within one month she had TSH: 0.7 uUI/ml and was completely recovered psychiatrically. She has been well since then, with risperidone in the first 8 months, and without it for 10 months now. CONCLUSION: This case report is a reminder of the necessity of checking thyroid status as part of clinical assessment of psychoses. It also supports the hypothesis that antithyroid drugs may have severe psychiatric consequences, especially when they lead to an acute change of thyroid status.

INTRODUÇÃO: Disfunções tireoidianas têm sido frequentemente associadas a diversas manifestações psiquiátricas. Séries e relatos de caso sugerem o possível papel da alteração aguda do status tireoidiano na vigência dos sintomas psicóticos. MÉTODOS: Relato de caso e revisão de literatura. RESULTADOS: Uma mulher de 45 anos sem antecedentes psiquiátricos foi trazida para Unidade de Emergência Referenciada com episódio psicótico, marcado por delírios paranoides, que se desenvolveram gradualmente nos dois meses anteriores. Ela tinha sido tratada, em outro serviço, por hipertireoidismo durante cinco anos com metimazol 40 mg/d, com aderência ruim. Um mês antes do início dos sintomas psicóticos, o metimazol foi aumentado para 60 mg/d, dose que ela estava tomando corretamente. Cinco meses antes ela tinha TSH: 0,074 uUI/ml e T4 livre: 1,3 ng/dl. Na admissão, encontraram-se aumento difuso da glândula, TSH: 70,9 uUI/ml e T4 livre: 0,03 ng/dl. TC de crânio estava normal. Foi hospitalizada por diagnóstico de psicose secundária ao hipotireoidismo, suspenso o metimazol e introduzidas levotiroxina (até 75 µg/d) e risperidona (2 mg/d). A paciente teve rápida remissão e recebeu alta após 15 dias. Um mês após ela apresentava TSH: 0,7 uUI/ml, com remissão completa da psicose. Ela permaneceu bem, com risperidona nos oito meses seguintes e sem a medicação há 10 meses. CONCLUSÃO: Este relato de caso é um alerta para a necessidade de investigar a função tireoidiana como parte do manejo clínico da psicose. Também reforça a hipótese de que drogas antitireoidianas podem ter graves consequências psiquiátricas, especialmente quando levam à mudança aguda do status tireoidiano.