Emerging drugs to reduce abnormal ß-amyloid protein in Alzheimer's disease patients.

INTRODUCTION: Currently available drugs against Alzheimer's disease (AD) target cholinergic and glutamatergic neurotransmissions without affecting the underlying disease process. Putative disease-modifying drugs are in development and target ß-amyloid (Aß) peptide and tau protein, the principal neurophatological hallmarks of the disease. Areas covered: Phase III clinical studies of emerging anti-Aß drugs for the treatment of AD were searched in US and EU clinical trial registries and in the medical literature until May 2016. Expert opinion: Drugs in Phase III clinical development for AD include one inhibitor of the ß-secretase cleaving enzyme (BACE) (verubecestat), three anti-Aß monoclonal antibodies (solanezumab, gantenerumab, and aducanumab), an inhibitor of receptor for advanced glycation end products (RAGE) (azeliragon) and the combination of cromolyn sodium and ibuprofen (ALZT-OP1). These drugs are mainly being tested in subjects during early phases of AD or in subjects at preclinical stage of familial AD or even in asymptomatic subjects at high risk of developing AD. The hope is to intervene in the disease process when it is not too late. However, previous clinical failures with anti-Aß drugs and the lack of fully understanding of the pathophysiological role of Aß in the development of AD, put the new drugs at substantial risk of failure.

[Predementia syndromes and mild cognitive impairment: diagnosis and progression to dementia]. / Sindromi pre-demenziali e deficit cognitivo lieve: diagnosi e progressione verso la demenza.

Different diagnostic criteria and terms have been proposed to describe clinical predementia syndromes in the elderly, although the epidemiology of these syndromes has not been thoroughly investigated. Particular interest in Mild Cognitive Impairment (MCI) arises from the fact that MCI is thought to be a prodromal phase and therefore highly predictive of subsequent Alzheimer's disease (AD). Several studies have suggested that most of the patients who met the MCI criteria will progress to AD, but rates of conversion to AD and dementia vary widely among studies, partly because of the characteristics of the population studied and the length of follow-up. Furthermore, recent findings suggest that in population-based studies the MCI classification is unstable, in contrast with clinic-based studies where progression is more uniform.