Nonsteroidal Anti-inflammatory Drugs Offer No Benefit to People with Alzheimer Disease
]]>Alzheimer disease (AD)]]> is a devastating neurologic condition that affects more than 4 million Americans—predominately those over the age of 65. In AD, nerve cells in the brain are progressively destroyed. This destruction causes dementia, which begins as a decline in memory and eventually leads to the disintegration of intellectual skills, personality, and the ability to function in everyday life.
The exact cause of AD has yet to be determined. However, inflammation has been the subject of much study. Many epidemiologic and laboratory studies strongly suggest that inflammation damages neurons, leading to the development of AD. And therefore, drugs that reduce inflammation would also reduce the incidence and/or severity of AD. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used to treat inflammation. They work by blocking the action of two types of enzymes: COX-1 and COX-2. Newer forms of NSAIDS, such as rofecoxib, inhibit only COX-2 enzymes and typically cause fewer side effects than the older forms of NSAIDs, such as naproxen (which inhibit both COX-1 and COX-2).
A study published in the June 4, 2003 issue of the Journal of the American Medical Association found that treatment with NSAIDs did not slow the rate of cognitive decline in people with mild-to-moderate forms of AD, as compared with placebo.
About the Study
This study is part of the Alzheimer’s Disease Cooperative Study (ACDS); participants were recruited from 40 treatment centers affiliated with the ACDS. The study group included 351 people over the age of 50 with mild-to-moderate AD, which was defined as a score between 13 and 26 on the Mini-Mental State Examination (MMSE). The MMSE is a screening tool commonly used to assess cognitive function.
The 351 volunteers were randomly divided into three groups: placebo, rofecoxib (25 milligrams [mg] per day), and naproxen sodium (220 mg per day). Tests to measure mental and behavioral function were done at the beginning of the study and at months 1, 3, 6, 9, 12, and 14.
Results from one particular test—The Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog)—were the primary means of comparison in this trial. The ADAS-Cog measures cognitive abilities such as memory, attention, reasoning, and language. This test was given to all participants at the beginning of the trial and at the end of one year. The change in score over one year was compared among the three groups.
The volunteers were also given several other tests to assess quality of life, activities of daily living, and other factors that may be affected by AD.
Among people with mild-to-moderate AD, taking NSAIDs for one year did not provide any benefit over taking placebo. The one-year change in ADAS-Cog scores did not differ significantly among the three groups, showing that neither rofecoxib nor naproxen slowed the decline in cognitive function characteristic of AD. Quality of life, activities of daily living, and other measures of health and well-being were also unaffected by NSAID treatment.
Although these findings seem to dismiss NSAIDs as a possible therapy for AD, there are a few limitations to the study. For example, higher doses of NSAIDs than those given here may be necessary to achieve benefits, or the drugs may need to be taken for longer than one year. Also, only two NSAIDs were studied in this trial; other NSAIDs may exert different effects on the course of AD. Another important consideration is that this study’s participants already had mild or moderate AD; it is still possible that people without AD who take NSAIDs regularly may be protected from subsequently developing the disease.
How Does This Affect You?
The clear lack of benefit seen here coupled with the possibility of side effects (such as dizziness, fatigue, dry mouth, high blood pressure, and gastrointestinal bleeding) indicate that the NSAIDs rofecoxib and naproxen should not be taken with the intent to slow the decline of mild-to-moderate AD. However, the role of NSAIDs in AD prevention was not examined in this trial and is still being studied.
The findings of this trial are frustrating for many people, as the treatment options currently available for managing AD are often disappointing. Drugs called cholinesterase inhibitors can temporarily delay the worsening of memory symptoms. Other drugs can be prescribed to treat behavioral symptoms, such as ]]>insomnia]]> , ]]>depression]]> , and aggression. If you or someone you care for is dealing with AD, talk with your doctor about the options.
National Institute of Neurological Disorders and Stroke
National Institute on Aging
Aisen PS, Schaefer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression. A randomized controlled trial. JAMA . 2003;289:2819-2826.
Launer LJ. Nonsteroidal anti-inflammatory drugs and Alzheimer disease. What’s next? [Editorial]. JAMA . 2003;289:2865-2867.
Last reviewed June 5, 2003 by ]]>Richard Glickman-Simon, MD]]>
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