Treatment of the mild cognitive impairment (MCI).
According to Evidence-Based-Medicine, any proposal for the rationale treatment of mild cognitive impairment (MCI) must be based on the results of double-blind, randomized clinical trials (RCTs). However, since MCI at the present time does not constitute a homogeneous clinical syndrome, it is still inappropriate to propose a specific drug treatment. Moreover, RCTs assessing the therapeutic value of acetylcholinesterase-inhibitors (AChEIs) are negative either trying to improve symptoms (memory performance) or preventing the conversion from MCI to real Alzheimer's Disease (AD). The same negative results were obtained with drugs targeting some systems considered as the early steps of the pathophysiological cascade leading to dementia: non-steroidal anti-inflammatory compounds (rofecoxib), sex steroid hormones (testosterone, estrogens), or antioxidants (tocopherol). Either MCI is considered as the very early phase of development of AD (and then the treatments will aim at preventively antagonizing the hallmarks of the disease) or MCI is a new entity (and then the drugs will target the associated neurochemical disturbances such as tau protein or soluble Abeta oligomers); MCI could also be considered as a monosymptomatic syndrome (amnesia) leading to the development of pure pro-mnestic drugs. These three hypotheses will be presented on the basis of the neurobiology and the pharmacology, and examples of potentially active candidates will be discussed.
Allain
Hervé
H
Laboratory of Experimental and Clinical Pharmacology and Centre Mémoire Ressources Recherche de Bretagne, Faculté de Médecine, 2 avenue du Professeur Léon Bernard, Rennes Cedex, France.
Bentué-Ferrer
Danièle
D
Akwa
Yvette
Y
D000368:Aged; D000647:Amnesia / Q000523:psychology / Q000628:therapy; D000682:Amyloid / Q000037:antagonists & inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000523:psychology / Q000628:therapy*; D018491:Dopamine Agonists / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011954:Receptors, Dopamine / Q000187:drug effects
D000682:Amyloid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D000697:Central Nervous System Stimulants; D002800:Cholinesterase Inhibitors; D018491:Dopamine Agonists; D012739:Gonadal Steroid Hormones; D011954:Receptors, Dopamine