Experimental approaches to cognitive disturbance in Alzheimer's disease

This paper reviews available and potential treatments for the cognitive disturbances associated with Alzheimer's disease. The neurochemical, neuropathological, and molecular-biological abnormalities associated with this disorder, as well as possible sites for pharmacological intervention, are discussed. These sites include genetic alterations in apolipoprotein E, amyloid precursor protein, and presenilin. Additionally, modification of amyloid processing, tau processing, and calcium regulation may have a role in future treatment. Intriguing epidemiological findings involving antiinflammatories, antioxidants, and estrogen for the cognitive deficits associated with Alzheimer's disease suggest the need for clinical trials of these agents. The current status of cholinesterase inhibitors, muscarinic receptor agonists, nicotine, and adrenergic and glutaminergic approaches to treatment are described.