Effect of non-steroidal anti-inflammatory drugs on natural killer cell activity in patients with dementia.
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.


OBJECTIVE
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).


CONCLUSIONS
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.
Aizen
Efraim
E
Department of Geriatrics, Fliman Geriatric Hospital, and Skin Research Laboratories, Technion Faculty of Medicine, Haifa, Israel. eaizen_il@yahoo.com
Kagan
Genady
G
Assy
Bedia
B
Iobel
Ranit
R
Bershadsky
Yakov
Y
Gilhar
Amos
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D002544:Cerebral Infarction; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D007052:Ibuprofen