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Published in: BMC Geriatrics 1/2005

Open Access 01-12-2005 | Research article

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

Authors: Agustín G Yip, Robert C Green, Matthew Huyck, L Adrienne Cupples, Lindsay A Farrer, for the MIRAGE Study Group

Published in: BMC Geriatrics | Issue 1/2005

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Abstract

Background

Nonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity.

Methods

The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier.

Results

NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans.

Conclusions

NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed.
Appendix
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Literature
1.
go back to reference Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MM, Hofman A: Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam Study. Neurology. 1995, 45: 1441-1445.CrossRefPubMed Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MM, Hofman A: Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam Study. Neurology. 1995, 45: 1441-1445.CrossRefPubMed
2.
go back to reference Anthony JC, Breitner JC, Zandi PP, Meyer MR, Jurasova I, Norton MC, Stone SV: Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: the Cache County study. Neurology. 2000, 54: 2066-2071.CrossRefPubMed Anthony JC, Breitner JC, Zandi PP, Meyer MR, Jurasova I, Norton MC, Stone SV: Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: the Cache County study. Neurology. 2000, 54: 2066-2071.CrossRefPubMed
3.
go back to reference Broe GA, Grayson DA, Creasey HM, Waite LM, Casey BJ, Bennett HP, Brooks WS, Halliday GM: Anti-inflammatory drugs protect against Alzheimer's disease at low doses. Arch Neurol. 2000, 57: 1586-1591. 10.1001/archneur.57.11.1586.CrossRefPubMed Broe GA, Grayson DA, Creasey HM, Waite LM, Casey BJ, Bennett HP, Brooks WS, Halliday GM: Anti-inflammatory drugs protect against Alzheimer's disease at low doses. Arch Neurol. 2000, 57: 1586-1591. 10.1001/archneur.57.11.1586.CrossRefPubMed
4.
go back to reference The Canadian Study of Health and Aging: risk factors for Alzheimer's disease in Canada. Neurology. 1994, 44: 2073-2080. The Canadian Study of Health and Aging: risk factors for Alzheimer's disease in Canada. Neurology. 1994, 44: 2073-2080.
5.
go back to reference in 't Veld BA, Launer LJ, Hoes AW, Ott A, Hofman A, Breteler MM, Stricker BH: NSAIDs and incident Alzheimer's disease. The Rotterdam Study. Neurobiol Aging. 1998, 19: 607-611. 10.1016/S0197-4580(98)00096-7.CrossRefPubMed in 't Veld BA, Launer LJ, Hoes AW, Ott A, Hofman A, Breteler MM, Stricker BH: NSAIDs and incident Alzheimer's disease. The Rotterdam Study. Neurobiol Aging. 1998, 19: 607-611. 10.1016/S0197-4580(98)00096-7.CrossRefPubMed
6.
go back to reference Stewart WF, Kawas C, Corrada M, Metter EJ: Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997, 48: 626-632.CrossRefPubMed Stewart WF, Kawas C, Corrada M, Metter EJ: Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997, 48: 626-632.CrossRefPubMed
7.
go back to reference in't Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH: Nonsteroidal anti-inflammatory drugs and risk of Alzheimer's disease. N Engl J Med. 2001, 345: 1515-1521. 10.1056/NEJMoa010178.CrossRef in't Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH: Nonsteroidal anti-inflammatory drugs and risk of Alzheimer's disease. N Engl J Med. 2001, 345: 1515-1521. 10.1056/NEJMoa010178.CrossRef
8.
go back to reference Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I: Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002, 156: 445-453. 10.1093/aje/kwf074.CrossRefPubMed Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I: Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002, 156: 445-453. 10.1093/aje/kwf074.CrossRefPubMed
9.
go back to reference Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC, Cache County Study Investigators: Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology. 2002, 59: 880-886.CrossRefPubMed Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC, Cache County Study Investigators: Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology. 2002, 59: 880-886.CrossRefPubMed
10.
go back to reference Breitner JC, Gau BA, Welsh KA, Plassman BL, McDonald WM, Helms MJ, Anthony JC: Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study. Neurology. 1994, 44: 227-232.CrossRefPubMed Breitner JC, Gau BA, Welsh KA, Plassman BL, McDonald WM, Helms MJ, Anthony JC: Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study. Neurology. 1994, 44: 227-232.CrossRefPubMed
11.
go back to reference Beard CM, Waring SC, O'Brien PC, Kurland LT, Kokmen E: Nonsteroidal anti-inflammatory drug use and Alzheimer's disease: a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc. 1998, 73: 951-955.CrossRefPubMed Beard CM, Waring SC, O'Brien PC, Kurland LT, Kokmen E: Nonsteroidal anti-inflammatory drug use and Alzheimer's disease: a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc. 1998, 73: 951-955.CrossRefPubMed
12.
go back to reference Henderson AS, Jorm AF, Christensen H, Jacomb PA, Korten AE: Aspirin, anti-inflammatory drugs and risk of dementia. Int J Geriatr Psychiatry. 1997, 12: 926-930. 10.1002/(SICI)1099-1166(199709)12:9<926::AID-GPS665>3.3.CO;2-P.CrossRefPubMed Henderson AS, Jorm AF, Christensen H, Jacomb PA, Korten AE: Aspirin, anti-inflammatory drugs and risk of dementia. Int J Geriatr Psychiatry. 1997, 12: 926-930. 10.1002/(SICI)1099-1166(199709)12:9<926::AID-GPS665>3.3.CO;2-P.CrossRefPubMed
13.
go back to reference Lautenschlager NT, Cupples LA, Rao VS, Auerbach SA, Becker R, Burke J, Chui H, Duara R, Foley EJ, Glatt SL, Green RC, Jones R, Karlinsky H, Kukull WA, Kurz A, Larson EB, Martelli K, Sadovnick AD, Volicer L, Waring SC, Growdon JH, Farrer LA: Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?. Neurology. 1996, 46: 641-650.CrossRefPubMed Lautenschlager NT, Cupples LA, Rao VS, Auerbach SA, Becker R, Burke J, Chui H, Duara R, Foley EJ, Glatt SL, Green RC, Jones R, Karlinsky H, Kukull WA, Kurz A, Larson EB, Martelli K, Sadovnick AD, Volicer L, Waring SC, Growdon JH, Farrer LA: Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?. Neurology. 1996, 46: 641-650.CrossRefPubMed
14.
go back to reference Farrer LA, Cupples LA, Blackburn S, Kiely DK, Auerbach S, Growdon JH, Connor-Lacke L, Karlinsky H, Thibert A, Burke JR: Interrater agreement for diagnosis of Alzheimer disease: the MIRAGE Study. Neurology. 1994, 44: 652-656.CrossRefPubMed Farrer LA, Cupples LA, Blackburn S, Kiely DK, Auerbach S, Growdon JH, Connor-Lacke L, Karlinsky H, Thibert A, Burke JR: Interrater agreement for diagnosis of Alzheimer disease: the MIRAGE Study. Neurology. 1994, 44: 652-656.CrossRefPubMed
15.
go back to reference Demissie S, Green RC, Mucci L, Tziavas S, Martelli K, Bang K, Coons L, Bourque S, Buchillon D, Johnson K, Smith T, Sharrow N, Lautenschlager N, Friedland R, Cupples LA, Farrer LA: Reliability of information collected by proxy in family studies of Alzheimer disease. Neuroepidemiology. 2001, 20: 105-111. 10.1159/000054768.CrossRefPubMed Demissie S, Green RC, Mucci L, Tziavas S, Martelli K, Bang K, Coons L, Bourque S, Buchillon D, Johnson K, Smith T, Sharrow N, Lautenschlager N, Friedland R, Cupples LA, Farrer LA: Reliability of information collected by proxy in family studies of Alzheimer disease. Neuroepidemiology. 2001, 20: 105-111. 10.1159/000054768.CrossRefPubMed
16.
go back to reference McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group. Neurology. 1984, 34: 939-944.CrossRefPubMed McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group. Neurology. 1984, 34: 939-944.CrossRefPubMed
17.
go back to reference Brandt J, Spencer M, Folstein M: The telephone interview for cognitive status. Neuropsychiatr Neuropsychol Behav Neurol. 1988, 1: 111-117. Brandt J, Spencer M, Folstein M: The telephone interview for cognitive status. Neuropsychiatr Neuropsychol Behav Neurol. 1988, 1: 111-117.
18.
go back to reference Welsh KA, Breitner JCS, Magruder-Habib KM: Detection of dementia in the elderly using telephone screening of cognitive status. Neuropsychiatr Neuropsychol Behav Neurol. 1993, 6: 103-110. Welsh KA, Breitner JCS, Magruder-Habib KM: Detection of dementia in the elderly using telephone screening of cognitive status. Neuropsychiatr Neuropsychol Behav Neurol. 1993, 6: 103-110.
19.
go back to reference Zeger SL, Liang KY: Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 1986, 42: 121-130.CrossRefPubMed Zeger SL, Liang KY: Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 1986, 42: 121-130.CrossRefPubMed
20.
go back to reference Breitner JC, Wyse BW, Anthony JC, Welsh-Bohmer KA, Steffens DC, Norton MC, Tschanz JT, Plassman BL, Meyer MR, Skoog I, Khachaturian A: APOE-ε4 count predicts age when prevalence of AD increases, then declines: The Cache County Study. Neurology. 1999, 53: 321-331.CrossRefPubMed Breitner JC, Wyse BW, Anthony JC, Welsh-Bohmer KA, Steffens DC, Norton MC, Tschanz JT, Plassman BL, Meyer MR, Skoog I, Khachaturian A: APOE-ε4 count predicts age when prevalence of AD increases, then declines: The Cache County Study. Neurology. 1999, 53: 321-331.CrossRefPubMed
21.
go back to reference Ophir G, Meilin S, Efrati M, Chapman J, Karussis D, Roses A, Michaelson DM: Human apoE3 but not apoE4 rescues impaired astrocyte activation in apoE null mice. Neurobiol Dis. 2003, 12: 56-64. 10.1016/S0969-9961(02)00005-0.CrossRefPubMed Ophir G, Meilin S, Efrati M, Chapman J, Karussis D, Roses A, Michaelson DM: Human apoE3 but not apoE4 rescues impaired astrocyte activation in apoE null mice. Neurobiol Dis. 2003, 12: 56-64. 10.1016/S0969-9961(02)00005-0.CrossRefPubMed
22.
go back to reference Martin BK, Meinert CL, Breitner JC, ADAPT Research Group: Double placebo design in a prevention trial for Alzheimer's disease. Control Clin Trials. 2002, 23: 93-99. 10.1016/S0197-2456(01)00189-1.CrossRefPubMed Martin BK, Meinert CL, Breitner JC, ADAPT Research Group: Double placebo design in a prevention trial for Alzheimer's disease. Control Clin Trials. 2002, 23: 93-99. 10.1016/S0197-2456(01)00189-1.CrossRefPubMed
Metadata
Title
Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study
Authors
Agustín G Yip
Robert C Green
Matthew Huyck
L Adrienne Cupples
Lindsay A Farrer
for the MIRAGE Study Group
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2005
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/1471-2318-5-2

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