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.

Resumo Os inibidores das colinesterases estão entre as principais drogas aprovadas para tratamento da doença de Alzheimer (DA). Rivastigmina na forma de adesivo transdérmico é um método alternativo de liberação e pode fornecer uma maior aderância ao tratamento. Objetivos: Conduzir uma abordagem preliminar dos efeitos neurocognitivos e biológicos da rivastigmina oral e transdérmica em pacientes com DA e identificar um potencial marcador biológico e demonstrar uma possível relação entre níveis de esterases e escores de comportamento de pacientes com DA. Métodos: Quarenta pacientes com DA com inibidores de colinesterases foram avaliados usando o MEEM e o INP e colhidas amostras para determinar seus níveis séricos de AChE e BuChE por 180 dias. Resultados: As diferenças obtidas entre as formas oral e transdérmica, avaliadas pelo MEEM e INP não diferiram em três ocasiões (0, 90 e 180 dias). Todavia, os níveis de BuChE no grupo transdérmico diferiu significativamente (p<0.0004) comparados ao grupo de administração oral em 90 dias. Conclusão: O uso do tartarato de rivastigmina, forma transdérmica reduziu significativamente os níveis de BuChE nos pacientes estudados com DA.

Abstract Cholinesterase inhibitors (ChE-Is) are among the main drugs approved for the treatment of Alzheimer's disease (AD). Rivastigmine in the form of a transdermal patch is an alternative delivery method, and can give greater treatment compliance. Objectives: To conduct a preliminary assessment of the neurocognitive and biological effects of oral and transdermal Rivastigmine in patients with AD and to identify a potential biological marker and demonstrate a possible relationship between esterase levels and behavioral scores of AD patients. Methods: Forty patients with AD were treated with cholinesterase inhibitors (ChE-Is), evaluated using the MMSE and NPI, and simultaneously sampled to determine their serum levels of AChE and BuChE for 180 days. Results: The differences obtained between oral and transdermal forms, as assessed by the MMSE and NPI scores of the AD patients, were not significant at the three time points examined (0, 90, and 180 days). However, serum BuChE levels of the transdermal group differed significantly (p<0.0004) compared with those of the oral group at 90 days. Conclusion: Use of a transdermal ChE-I, rivastigmine tartrate significantly reduced BuChE levels in the AD patients studied.