Lleo_2006_Annu.Rev.Med_57_513

Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects approximately 4.5 million people in the United States. The mainstays of current pharmacotherapy for AD are compounds aimed at increasing the levels of acetylcholine in the brain, thereby facilitating cholinergic neurotransmission through inhibition of the cholinesterases. These drugs, known as acetylcholinesterase inhibitors (AChEIs), were first approved by the U.S. Food and Drug Administration (FDA) in 1995 based on clinical trials showing modest symptomatic benefit on cognitive, behavioral, and global measures. In 2004 the FDA approved memantine, an NMDA antagonist, for treating dementia symptoms in moderate to severe AD cases. In clinical practice, memantine may be co-administered with an AChEI, although neither drug individually or in combination affects the underlying pathophysiology of dementia. Dementia in AD results from progressive synaptic loss and neuronal death. As knowledge of the mechanisms responsible for neurodegeneration in AD increases, it is anticipated that neuroprotective drugs to slow or prevent neuronal dysfunction and death will be developed to complement current symptomatic treatments.