Types of Antiinflammatory Agents

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Anti-inflammatory medications are of two types: steroidal and nonsteroidal. It may seem odd that steroids, which in high concentrations can damage the hippocampus, can be therapeutic for patients with dementia. However, the fact that inflammation does occur in the brains of these patients suggests that steroids, which have extremely powerful anti-inflammatory properties, may indeed be effective treatments. Drs. Paul Aisen and Ken Davis at the Mount Sinai Medical Center in New York certainly think so, and they recently completed a placebo-controlled clinical trial using prednisone, a synthetic steroid, in Alzheimer's disease. However, the trial results were negative: prednisone showed no advantage over placebo in these patients.

The other approach is to use nonsteroidal anti-inflammatory medications (NSAIDs) like acetylsalicylic acid (aspirin), indomethacin (Indocin), or ibuprofen (Motrin). Acetaminophen (Tylenol) has weak anti-inflammatory properties compared to aspirin, even though it has similar pain-killing strength.

Lessons from Arthritis

In rheumatoid arthritis, the kind that causes swelling and deformity of the fingers and toes, as well as the hands and feet, the body's immune system mistakenly identifies joint tissue parts as alien and attacks them with a vengeance. Since many people who suffer from this disease regularly have to take high doses of anti-inflammatory medications, the question arises: do these people have a lower prevalence of dementia, especially Alzheimer's disease, compared to the rest of the population?

Patrick McGeer and his colleagues at the University of British Columbia in Canada conducted a comprehensive review of seventeen studies conducted in nine countries to evaluate the associations between the use of anti-inflammatory medications and Alzheimer's disease. They concluded that the use of either NSAIDs or steroids cuts the risk of having Alzheimer's disease by approximately half. This finding held up whichever way the data were analyzed: looking at the presence of rheumatoid arthritis alone, the use of either NSAIDs or steroids, or a combination of these treatments. Some of these effects of nonsteroidal medications in Alzheimer's disease and stroke may also apply to treatment and prevention of mild memory loss.

Taking Anti-inflammatory Agents for Memory Loss

In a survey of people living at home, John Breitner of Duke University discovered that elderly people who were taking anti-inflammatory agents like aspirin and ibuprofen were less likely to get dementia than the rest of the population. Breitner has continued this work after moving to Johns Hopkins, and has found a protective effect for NSAIDs against dementia in a large study of twins. Other reports from Johns Hopkins showed that Alzheimer's patients who took NSAIDs performed better on neuropsychological tests. Approaching the same problem from a different angle, Japanese researchers demonstrated that the use of dapsone, which is an antileprosy agent with anti-inflammatory properties, was associated with a significantly lower risk of developing Alzheimer's disease.

Placebo-controlled trials using both over-the-counter and prescription anti-inflammatory medications have involved very few subjects, but the results are quite intriguing. J. Rogers and colleagues at the Sun Health Research Institute in Arizona conducted a six-month study using the NSAID indomethacin (Indocin) and placebo in twenty-eight patients with Alzheimer's disease. Patients on indomethacin showed an average 1.3 percent improvement in cognitive performance compared to an 8.4 percent worsening in the placebo group, a significant difference.

The Pros and Cons of Aspirin

Aspirin remains the top choice among anti-inflammatory agents, because it has two more promemory actions: antioxidant activity by trapping hydroxyl radicals, and anticlotting property that helps prevent stroke.

Personal experience makes me a trifle wary of recommending aspirin for everyone. A few years ago, after my mother had a balloon angioplasty for unstable angina, her cardiologist started her on a single tablet of aspirin 325 mg daily. A few days later, she noticed blood in the stools. I suggested to her cardiologist that the aspirin be stopped. Barely five days had elapsed since the angioplasty, so he was loath to discontinue the aspirin, because he wanted to prevent recurrence of blood clots in the coronary arteries that supply the heart. Eventually, after considerable coaxing from me, he agreed to reduce my mother's dose to a baby aspirin (81 mg) daily. A couple of days later, she had further, massive lower gastrointestinal bleeding, and I rushed her to the emergency room. It was touch and go for a while, and she required six pints of blood in the intensive care unit before she was stabilized. After an endoscopic examination, the consultant gastroenterologist found evidence of bleeding and educated me about the fact that aspirin can cause bleeding from not only the stomach but also lower down in the intestines. This explained why my mother had both upper and lower gastrointestinal bleeding that was so severe it had dropped her hemoglobin to one-third the normal concentration in the blood. She was then switched to ticlopidine (Ticlid) and later to clopidogrel (Plavix), which have anticoagulant properties similar to aspirin. Obviously, she has not been within a hundred feet of an aspirin tablet since that time.

While this degree of exquisite sensitivity to aspirin is quite rare, I hope this makes you realize that even aspirin is not an entirely harmless medication. In fact, if aspirin were presented today to the FDA as a new drug, it might not be approved because of its high toxicity.

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