Alzheimer's disease: pathophysiology and pharmacotherapy

Alzheimer's disease (AD) is the leading cause of dementia in mid-to-late life, and is estimated to afflict approximately 20 million people worldwide. There are considerable financial, social and emotional costs associated with the burden of caring for patients with AD. Clinically, AD is characterized by an insidious loss of memory, associated functional decline and behavioral disturbances. Many neurotransmitter systems are also affected; however, degeneration in the cholinergic system occurs earlier and more consistently than in other systems. As cholinergic function is required for short-term memory function, it is believed that the cholinergic deficit in AD is also responsible for much of the short-term memory deficit. The cholinergic hypothesis of AD has led to the development of a number of strategies to enhance the failing cholinergic neurons and thus the neurotransmitter acetylcholine (ACh). In general, appropriate management of AD patients with antioxidants, acetylcholinesterase inhibitors (AChEIs) and psychotropic agents can slow the progression of the disease, improve cognition, and reduce behavioral disturbances, which may enhance patient and caregiver quality-of-life and delay nursing home residence.