Pharmacotherapy of cognitive dysfunctions in Alzheimer’s disease: current strategies and experimental therapies

Zakład Psychologii Lekarskiej, Wydział Nauk o Zdrowiu, Uniwersytet Medyczny w Łodzi

AKTUALN NEUROL 2013, 13 (4), p. 287–294

Currently available methods of pharmacological treatment of cognitive dysfunction related to Alzheimer’s disease (AD) are based on augmentation of cholinergic neurotransmission (by inhibiting activity of cholinesterases) or modulation of glutamatergic transmission (by acting on NMDA receptor). Both classes of drug exhibit clinically significant (though modest) symptomatic improvement not only considering cognition but also behaviour and activities of daily living. Whether or not they modify natural course of the disease, is not clearly confirmed by result of rigorously planned clinical trials and is currently considered unlikely. With the development of genetic and molecular studies on the pathogenesis of AD novel treatment targets emerged recently, importantly these based on amyloid cascade hypothesis and τ protein phosphorylation. Unfortunately, the so far undertaken clinical trials yielded disappointing results, either proving not be effective or showing unfavourable side effects profile. The most commonlyproposed explanations of these failures include starting trials too late during the disease process and/or insufficiently specific strategies of patients’ selection resulting in inclusion of subjects suffering from other than AD cognitive dysfunctions. Biomarkers of disease-specific process are currently leading answer to the experienced trials failures as they are starting to be routinely used in novel studies.

Keywords: dementia, cognitive dysfunction, cholinesterase inhibitors, memantine, immunotherapy