March 10, 1997
In a 15 year study, anti-inflammatory drugs such as ibuprofen, taken for as little as 2 years, appear to reduce the risk of Alzheimer's disease (AD). Acetaminophen, with no anti-inflammatory activity, had no effect on the risk of AD, while the third compound reviewed, aspirin, a potent anti-inflammatory agent, appeared to have little or no effect on the risk of AD within the limitations of this study.
The research, by scientists at the National Institute on Aging (NIA) and Johns Hopkins University, appears in the March 1997 issue of Neurology (Vol 48, No. 3, pp 626-632). The study was conducted by Walter F. Stewart, Ph.D. at Johns Hopkins School of Public Health, Claudia Kawas, M.D., and Maria Corrada at Johns Hopkins School of Medicine, and E. Jeffrey Metter, M.D., at the NIA, using data from NIA's Baltimore Longitudinal Study of Aging (BLSA).
Background
Other studies looking at the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on AD have shown a link between these drugs and reduction in the risk of AD. This study, however, is the first to look at a large number of patients over a substantial period of time as opposed to previous studies done at fixed points-in-time. This long-term, or longitudinal, study enabled the researchers to eliminate a number of biases that made earlier short-term studies less definitive, such as probable underreporting of NSAID use. Additionally, with this study, the longitudinal process gave the researchers the ability to determine whether the length of time that people used NSAIDs also played a role in the degree and progression of AD.
The BLSA was the key to making this research possible. Since 1958, the BLSA has examined over 2,300 people. The study characterized a large number of medical factors, including brain and mental function as well as signs of dementias such as AD. Close to a dozen tests currently are administered biennially to search for early signs of AD. Since 1978 the BLSA has tracked the use of NSAIDs by its participants, and since 1990 nurse practitioners have kept track even more rigorously of participant use of medications. These long-term tracking procedures lend this study a greater validity than previous research.
Inflammation and Alzheimer's Disease
According to Kawas, "many scientists now believe that inflammation may be an important component of the Alzheimer's disease process. The amyloid and protein plaques found in Alzheimer's patient's brains, which are hallmarks of the disease, may be indicative of an inflammatory response." Researchers believe that NSAIDs may influence inflammation by interfering with the actions of some proteins and thus lessening their harmful effects.
Reduction in Risk
The overall risk of AD in 1,686 participants from the BLSA who were taking NSAIDs (relative risk 0.5) was half the risk of those not taking NSAIDs. Relative risk declined from 0.65 in those with less than 2 years of reported NSAID use to 0.40 in those with 2 years or more of NSAIDs use which suggests a greater reduction in the risk of developing AD with longer NSAID use. As expected, there was no decreased risk seen with acetaminophen use since it has few or no anti-inflammatory properties. Aspirin use did not result in a statistically significant decrease in risk even over long periods of time. However, the researchers suggest that increased dosages of aspirin over longer periods of time might show some effect. Since the use of aspirin by study participants varied, definitive conclusions about aspirin's effects on AD await further study.
During the observation period from 1980 until 1995, NSAID use tripled among BLSA participants, with ibuprofen accounting for nearly half of the NSAIDs used, naprosyn followed at 15 percent, and a variety of other prescription and over-the-counter NSAIDs accounted for the remaining drugs. Aspirin use remained high through the period among roughly 40 percent of the BLSA participants, probably as a result of the reported benefits of low-dose aspirin for cardiovascular disease. The investigators think that dosage levels of aspirin may not have been sufficient to show any effect on central nervous system disorders.
Caution on Use of NSAIDs
The scientists caution that chronic use of NSAIDs may lead to a number of serious side effects, including peptic ulcers and impaired kidney function. To determine the effectiveness of prophylactic use of NSAIDs in people at high risk for AD, clinical trials are needed. "Currently, we don't know what interactions NSAIDs could have with other Alzheimer's drugs in the pipeline. What the effectiveness of NSAIDs tells us about the inflammatory response and the Alzheimer's disease process will be critically important to developing even better agents and approaches," according to Metter.
