ABSTRACT
BACKGROUND: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease. OBJECTIVES: To determine whether the use of NSAIDs is associated with natural killer activity alteration in AD and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people. METHODS: In this prospective open study four groups of subjects (AD, VD, non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment. RESULTS: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 +/- 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 +/- 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 +/- 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 +/- 4.4). While all examined subjects showed decreased NK cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia--from an average of 30.5 +/- 11.8% before treatment to 22.5 +/- 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001). CONCLUSION: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.
