Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer's disease

Alzheimer's disease (AD) is a worldwide problem that affects 5 million people in the United States alone. Until the approval of tacrine in the mid-1990s, there was no effective therapy for the cognitive symptoms of AD. Although cholinergic therapy provides modest but significant symptomatic relief, the development of effective disease-modifying therapy is essential. It has been demonstrated that a number of inflammatory processes are active in the brain of patients with AD, and therefore it is believed that an anti-inflammatory regimen may offer some degree of neuroprotection. Several studies have indicated that use Of nonsteroidal anti-inflammatory, drugs (NSAIDs) is associated with delayed onset and/or slowed cognitive decline in AD. Although not currently approved for this condition, recent findings have demonstrated that cyclooxygenase (COX)-2 is of primary, importance in the inflammatory response and may have a role in neurodegeneration. Therefore, selective COX-2 inhibitors (coxibs) may have an advantage over traditional NSAIDs as potential therapeutic agents in AD. The Alzheimer's Disease Cooperative Study (ADCS) is conducting an ongoing multicenter, double-blind, placebo-con trolled trial to determine whether rofecoxib, a coxib, or naproxen, a nonselective D, will slow the rate of cognitive and clinical decline in AD. This study, along with other clinical studies currently under way, will determine the utility of selective and nonselective COX inhibitors for the prevention and treatment of AD. (C) U.S. Cancer Pain Relief Committee, 2002.