NSAIDs for one year failed to show Alzheimer’s disease

Neither the selective cyclooxygenase-2inhibitor rofecoxib nor the nonselective NSAID naproxen slowed the rate of cognitive or functional decline in a one-year, placebo-controlled study of patients with Alzheimer’s disease, it was reported at the Eighth International Conference on Alzheimer’s disease and Related Disorders.

The findings were seen in a randomized trial of 351 subjects with mild to moderate Alzheimer’s disease, according to a professor of neurology at Georgetown University Washington. This is the latest finding from the National Institute on Aging-funded Alzheimer’s Disease Cooperative Study, designed to investigate the "inflammatory hypothesis" of the disorder. Previously, low-dose prednisone had no impact on disease progression in 138 subjects over one year.

Inflammatory mechanisms have been shown to contribute to neuronal injury in Alzheimer’s disease, and epidemiologic data support a role for NSAIDs in slowing the neuropathology of the disease. Yet "anti-inflammatory therapy remains an intriguing but unproven strategy for Alzheimer’s disease at present, said at the conference, sponsored by the Alzheimer’s Association. In the trial, patients were given either recoxib at 25mg/day, naproxen at 200mg twice daily, or placebo. Most patients were also taking cholinesterase inhibitors, and many were also on low-dose aspirin or vitamin E. Drop-out rates were similar among the three groups. At one year, declines in performances scores on the Alzheimer’s Disease Assessment Scale were not significantly different – a drop of 7.6 points in the refecoxib group, of 5.8 points for naproxen, and of 5.7 points with placebo. Also, there were no differences in decline on the Clinical Dementia Rating scale. The two active drug groups scored slightly better on the Activities of Daily Living scale, but this was probably due to the analgesic effect of the drugs.

There were also no differences between the groups in end points such as death or time-institutionalization. However, both serious and non-serious adverse events, particularly GI problems and stroke or transient ischemic attacks, were more common in the active drug groups. In all, there were 26 adverse events with refecoxib and 25 with naproxen, versus 15 with placebo. Although these and the previous findings form the Alzheimer’s Disease Cooperative Study do not support a treatment role for NSAIDs in Alzheimer’s, the drugs may still play a role in prevention. The National Institute on Aging has funded a trial to investigate that possibility. The 7-year study will involve four sites and enroll 2,625 cognitively normal subjects aged 72-88 who have family member with Alzheimer-like dementia. The non-selective NSAID ibuprofen and the selective COX-2 inhibitor celecoxib will be tested to see if either prevents Alzheimer’s disease or attenuates progressive age-related decline.