Alzheimer's disease (AD) lesions are characterized by the presence of numerous inflammatory proteins. This has led to the hypothesis that brain inflammation is a cause of neuronal injury in AD and that anti-inflammatory drugs may act as protective agents. Seventeen epidemiologic studies from nine different countries have now been published in which arthritis, a major indication for the use of anti-inflammatory drugs, or anti-inflammatory drugs themselves have been considered as risk factors for AD. Both factors appear to be associated with a reduced prevalence of AD. The small size of most studies has limited their individual statistical significance, but similarities in design have made it possible to evaluate combined results. We have used established methods of statistical meta-analysis to estimate the overall chance of individuals exposed to arthritis or anti-inflammatory drugs developing AD as compared with the general population. Seven case-control studies with arthritis as the risk factor yielded an overall odds ratio of 0.556 (p < 0.0001), while four case-control studies with steroids yielded odds ratios of 0.656 (p = 0.049) and three case-control studies with nonsteroidal anti-inflammatory drugs (NSAIDs) yielded an odds ratio of 0.496 (p = 0.0002). When NSAIDs and steroids were combined into a single category of anti-inflammatory drugs, the odds ratio was 0.556 (p < 0.0001). Population-based studies were less similar in design than case-control studies, complicating the process of applying statistical meta-analytical techniques. Nevertheless, population-based studies with rheumatoid arthritis and NSAID use as risk factors strongly supported the results of case-control studies. These data suggest anti-inflammatory drugs may have a protective effect against AD. Controlled clinical trials will be necessary to test this possibility.

To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.

The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson's disease (PD). Little is known, however, about the mechanism underlying the placebo effect. Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography, we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo. Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system.

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