Treatment of Alzheimer's disease: current status and new perspectives.
Alzheimer's disease (AD) is the most common neurodegenerative disorder and the most prevalent cause of dementia with ageing. Pharmacological treatment of AD is based on the use of acetylcholinesterase inhibitors, which have beneficial effects on cognitive, functional, and behavioural symptoms of the disease, but their role in AD pathogenesis is unknown. Other pharmacological therapies are becoming available--including the recently approved drug memantine, an NMDA channel blocker indicated for advanced AD. Here, we review clinical features of the available cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) including their pharmacological properties, the evidence for switching from one agent to another, "head to head" studies, and the emerging evidence for the use of memantine in AD. New therapeutic approaches--including those more closely targeted to the pathogenesis of the disease--will also be reviewed. These potentially disease modifying treatments include amyloid-beta-peptide vaccination, secretase inhibitors, cholesterol-lowering drugs, metal chelators, and anti-inflammatory agents.
Scarpini
Elio
E
Department of Neurological Sciences, Dino Ferrari Center and CEND, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. elio.scarpini@unimi.it
Scheltens
Philip
P
Feldman
Howard
H
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015913:Chelation Therapy; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007167:Immunotherapy; D008559:Memantine / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008559:Memantine