Cited by 1,196Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsInflammatory mediators and NSAID effects

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease

Open access

in 't Veld, Bas A., Ruitenberg, Annemieke, Hofman, Albert, Launer, Lenore J., van Duijn, Cornelia M., Stijnen, Theo, Breteler, Monique M.B., Stricker, Bruno H.C.·2001·New England Journal of Medicine

DOI 10.1056/nejmoa010178

Open this paper in CoChat — free account Open PDF

Abstract

BACKGROUND: Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, are inconsistent. METHODS: We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line, in 1991. To detect new cases of dementia, follow-up screening was performed in 1993 and 1994 and again in 1997 through 1999. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine Hz-receptor antagonists, antihypertensive agents, and hypoglycemic agents. RESULTS: During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. CONCLUSIONS: The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1056/nejmoa010178

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

“Mini-mental state”
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793
Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
Regression Models and Life-Tables
Cox, D. R. (1992) · Springer Series in Statistics · doi:10.1007/978-1-4612-4380-9_37 · Cited by 26,297
Vascular dementia: Diagnostic criteria for research studies: Report of the NINDS‐AIREN International Workshop*
Román, G. C., Tatemichi, T. K., Erkinjuntti, T., Cummings, J. L., Masdeu, J. C., Garcia, J. H., Amaducci, L., Orgogozo, J.-M., Brun, A., Hofman, A., et al. (1993) · Neurology · doi:10.1212/wnl.43.2.250 · Cited by 4,921
The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., & Glass, C. K. (1998) · Nature · doi:10.1038/34178 · Cited by 3,525
CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia
Roth, M., Tym, E., Mountjoy, C. Q., Huppert, F. A., Hendrie, H., Verma, S., & Goddard, R. (1986) · British Journal of Psychiatry · doi:10.1192/bjp.149.6.698 · Cited by 2,090
The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287
Risk of Alzheimer's disease and duration of NSAID use
Stewart, W. F., Kawas, C., Corrada, M., & Metter, E. J. (1997) · Neurology · doi:10.1212/wnl.48.3.626 · Cited by 1,132
Determinants of disease and disability in the elderly: The Rotterdam elderly study
Albert Hofman, D., Grobbee, D. E., de Jong, P. T. V. M., & Ouweland, F. A. V. D. (1991) · European Journal of Epidemiology · doi:10.1007/bf00145007 · Cited by 1,120

Flagged first, then by citations

Show all 44 references

Research works printed but not linked: 4

Brooks W, 1998, Neurobiol Aging, 19, S140
Kukull WA, 1994, Neurology, 44, A237
Cornelius C, 1998, Neurobiol Aging, 19, S28
Time-varying explanatory variables. In: Clayton D, Hills M. Statistical models in epidemiology. Oxford, England: Oxford University Press, 1993:307-18.

Sorted by citations

Items 701–800 of 1,000

Differences in ABCA1 R219K Polymorphisms and Serum Indexes in Alzheimer and Parkinson Diseases in Northern China
Ya, L., & Lu, Z. (2017) · Medical Science Monitor · doi:10.12659/msm.903636 · Cited by 23
WITHDRAWN: Revisiting the cholinergic hypothesis in Alzheimer's disease: Emerging evidence from translational and clinical research
Hampel, H. J., Mesulam, M. M., Cuello, A. C., Khachaturian, A. S., Farlow, M. R., Snyder, P. J., Giacobini, E., & Khachaturian, Z. S. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.08.016 · Cited by 25
Retracted
Is it All Said for NSAIDs in Alzheimer’s Disease? Role of Mitochondrial Calcium Uptake
Sanz‐Blasco, S., Calvo-Rodríguez, M., Caballero, E., García-Durillo, M., Núñez, L., & Villalobos, C. (2017) · Current Alzheimer Research · doi:10.2174/1567205015666171227154016 · Cited by 24
Inverse Relationship Between Alzheimer’s Disease and Cancer: How Immune Checkpoints Might Explain the Mechanisms Underlying Age-Related Diseases
Rogers, N. K., Romero, C., SanMartín, C. D., Ponce, D. P., Salech, F., López, M. N., Gleisner, M. A., Tempio, F., & Behrens, M. I. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190839 · Cited by 23
Disposition of flurbiprofen in man: influence of stereochemistry and age
Patel, B. K., Jackson, S., Swift, C. G., & Hutt, A. J. (2003) · Xenobiotica · doi:10.1080/00498250310001602739 · Cited by 23
Pharmacological effects of Ibuprofen on learning and memory,muscarinicreceptors gene expression and APP isoforms level in pre-frontal cortex of AlCl3-induced toxicity mouse model
Hashmi, A. N., Yaqinuddin, A., & Ahmed, T. (2014) · International Journal of Neuroscience · doi:10.3109/00207454.2014.922972 · Cited by 22
Treatment with Histone Deacetylase Inhibitor Attenuates Peripheral Inflammation-Induced Cognitive Dysfunction and Microglial Activation: The Effect of SAHA as a Peripheral HDAC Inhibitor
Takada, N., Nakamura, Y., Ikeda, K., Takaoka, N., Hisaoka‐Nakashima, K., Sanoh, S., Kotake, Y., Nakata, Y., & Morioka, N. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03367-1 · Cited by 21
Identification and drug-induced reversion of molecular signatures of Alzheimer’s disease onset and progression in AppNL-G-F, AppNL-F, and 3xTg-AD mouse models
Pauls, E., Bayod, S., Mateo, L., Alcalde, V., Juan-Blanco, T., Sánchez‐Soto, M., Saido, T. C., Saito, T., Berenguer, A., Attolini, C. S., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00983-y · Cited by 23
Current and Future Nano-Carrier-Based Approaches in the Treatment of Alzheimer’s Disease
Kumar, A., Sudevan, S. T., Nair, A. S., Singh, A. K., Kumar, S., Jose, J., Behl, T., Mangalathillam, S., Mathew, B., & Kim, H. (2023) · Brain Sciences · doi:10.3390/brainsci13020213 · Cited by 26
Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study
Tang, H., Guo, J. S., Shaaban, C. E., Zheng, F., Wu, Y., Magoč, T., Hu, X., Donahoo, W. T., DeKosky, S. T., & Bian, J. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13480 · Cited by 21
Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Endoplasmic Reticulum Stress and Immunological Stress in Pathogenesis of Alzheimer’s Disease
Hosoi, T., & Ozawa, K. (2012) · Journal of Pharmacological Sciences · doi:10.1254/jphs.11r09fm · Cited by 22
Geniposide attenuates Aβ 25–35 -induced neurotoxicity via the TLR4/NF-κB pathway in HT22 cells
Huang, X., Li, J., Tao, Y., Wang, X., Zhang, R.-L., Zhang, J., Su, Z., Huang, Q., & Deng, Y. (2018) · RSC Advances · doi:10.1039/c8ra01038b · Cited by 22
Risk of dementia among patients with Sjogren's syndrome: A nationwide population-based cohort study in Taiwan
Chen, H., Perng, W., Chiou, J., Wang, Y., Huang, J., & Wei, J. C.-C. (2018) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2018.06.007 · Cited by 22
RETRACTED ARTICLE: Exploring the Role of CLU in the Pathogenesis of Alzheimer’s Disease
Uddin, M. S., Kabir, M. T., Begum, M. M., Islam, M. S., Behl, T., & Ashraf, G. M. (2020) · Neurotoxicity Research · doi:10.1007/s12640-020-00271-4 · Cited by 22
Retracted
Electroacupuncture Ameliorates Neuroinflammation-Mediated Cognitive Deficits through Inhibition of NLRP3 in Presenilin1/2 Conditional Double Knockout Mice
Li, K., Shi, G., Zhao, Y., Chen, Y., Gao, J., Yao, L., Zhao, J., Li, H., Xu, Y., & Chen, Y. (2021) · Neural Plasticity · doi:10.1155/2021/8814616 · Cited by 23
Chymotrypsin‐like proteases contribute to human monocytic THP‐1 cell as well as human microglial neurotoxicity
Klegeris, A., & McGeer, P. L. (2005) · Glia · doi:10.1002/glia.20186 · Cited by 22
Neurones treated with cyclo-oxygenase-1 inhibitors are resistant to amyloid-β1-42
Bate, C., Veerhuis, R., Eikelenboom, P., & Williams, A. (2003) · Neuroreport · doi:10.1097/00001756-200311140-00018 · Cited by 22
Medication use to manage comorbidities for people with dementia: a systematic review
Page, A. T., Etherton‐Beer, C., Seubert, L., Clark, V., Hill, X., King, S., & Clifford, R. M. (2018) · Journal of Pharmacy Practice and Research · doi:10.1002/jppr.1403 · Cited by 23
Circadian rhythm, microglia-mediated neuroinflammation, and Alzheimer’s disease
Geng, F., Zhao, N., & Ren, Q. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106044 · Cited by 22
Aiding the discovery of new treatments for dementia by uncovering unknown benefits of existing medications
Kern, D. M., Cepeda, M. S., Lovestone, S., & Seabrook, G. R. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.07.012 · Cited by 21
“Similarly, prior research has found protective associations with use of nonsteroidal anti-inflammatory drugs [10] and potassium sparing diuretics [11], but in our study, these associations were not strong enough to be included in the results (e.”
BackgroundResult
ALZT-OP1: an experimental combination regimen for the treatment of Alzheimer’s disease
Lozupone, M., Berardino, G., Mollica, A., Sardone, R., Dibello, V., Zupo, R., Lampignano, L., Castellana, F., Bortone, I., Stallone, R., et al. (2022) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2022.2095261 · Cited by 22
NO‐flurbiprofen reduces amyloid‐β, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade
Abdul‐Hay, S. O., Luo, J., Asghodom, R. T., & Thatcher, G. R. J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06353.x · Cited by 21
“The potential of NSAIDs as AD therapeutics is supported by epidemiological studies that have reported a decreased risk of developing AD after chronic treatment with NSAIDs (Rich et al. 1995; Stewart et al. 1997; in t’ Veld et al. 2001).”
Background
Insufficient Resolution Response in the Hippocampus of a Senescence-Accelerated Mouse Model — SAMP8
Wang, X., Puerta, E., Cedazo-Mı́nguez, Á., Hjorth, E., & Schultzberg, M. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0346-z · Cited by 21
The effects of aging, housing and ibuprofen treatment on brain neurochemistry in a triple transgene Alzheimer’s disease mouse model using magnetic resonance spectroscopy and imaging
Choi, J., Carreras, I., Aytan, N., Jenkins-Sahlin, E., Dedeoglu, A., & Jenkins, B. G. (2014) · Brain Research · doi:10.1016/j.brainres.2014.09.067 · Cited by 21
“Epidemiologic studies of patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) for at least 24 months showed a large decreased subsequent relative risk of AD (in t’ Veld et al., 2001; Stewart et al., 1997).”
Background
[18F]-labeled isoindol-1-one and isoindol-1,3-dione derivatives as potential PET imaging agents for detection of β-amyloid fibrils
Lee, J. H., Byeon, S. R., Kim, Y. S., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.05.019 · Cited by 21
The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer’s disease modifying agent
Stock, N. S., Muñoz, B., Wrigley, J. D. J., Shearman, M. S., Beher, D., Peachey, J., Williamson, T. L., Bain, G., Chen, W., Jiang, X., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.01.033 · Cited by 21
Épidémiologie de la maladie d’Alzheimer
Dartigues, J., Berr, C., Helmer, C., & Letenneur, L. (2002) · médecine/sciences · doi:10.1051/medsci/20021867737 · Cited by 19
Neurocognitive Enhancement: Ethical Considerations for an Emerging Subspecialty
Bush, S. S. (2006) · Applied Neuropsychology · doi:10.1207/s15324826an1302_7 · Cited by 21
Effects of non-steroidal anti-inflammatory drugs on Aβ deposition in Aβ1–42 transgenic C. elegans
Morita, M., Osoda, K., Yamazaki, M., Shirai, F., Matsuoka, N., Arakawa, H., & Nishimura, S. (2009) · Brain Research · doi:10.1016/j.brainres.2009.08.002 · Cited by 21
Primary prevention trials in Alzheimer disease
Green, R. C., & DeKosky, S. T. (2006) · Neurology · doi:10.1212/wnl.67.9_suppl_3.s2 · Cited by 21
Preventing dementia
Purandare, N. B., Ballard, C. G., & Burns, A. S. (2005) · Advances in Psychiatric Treatment · doi:10.1192/apt.11.3.176 · Cited by 20
Alzheimer's Disease
Mandell, A. M., & Green, R. C. (2011) · Wiley eBooks · doi:10.1002/9781444344110.ch1 · Cited by 22
Long‐Term Exposure to Non‐Steroidal Anti‐Inflammatory Medication in Relation to Dementia Risk
Hofe, I. V., Stricker, B. H. C., Ikram, M. A., Wolters, F. J., & Ikram, M. A. (2025) · Journal of the American Geriatrics Society · doi:10.1111/jgs.19411 · Cited by 23
Self-citation
An analysis of omega-3 clinical trials and a call for personalized supplementation for dementia prevention
Castellanos-Perilla, N., Borda, M. G., Aarsland, D., & Barreto, G. E. (2024) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2024.2313547 · Cited by 25
The Role of Cardiovascular Risk Factors in Alzheimer's Disease
Ravona‐Springer, R., Davidson, M., & Noy, S. (2003) · CNS Spectrums · doi:10.1017/s109285290001926x · Cited by 20
Alzheimer’s Disease Genetics: A Dampened Microglial Response?
Chatila, Z. K., & Bradshaw, E. M. (2021) · The Neuroscientist · doi:10.1177/10738584211024531 · Cited by 20
Gene expression profiling and therapeutic interventions in neurodegenerative diseases: a comprehensive study on potentiality and limits
Benetti, F., Gustincich, S., & Legname, G. (2012) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2012.659661 · Cited by 22
Aspirin and tension-type headache
Farinelli, I., & Martelletti, P. (2006) · The Journal of Headache and Pain · doi:10.1007/s10194-006-0357-4 · Cited by 20
Anti-inflammatory agents in Alzheimer’s disease
Aisen, P. S. S. (2002) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-002-0066-6 · Cited by 20
Incretin-based therapeutics for the treatment of neurodegenerative diseases
Vear, A., Heneka, M. T., & Clemmensen, C. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01263-4 · Cited by 25
Preliminary Assessment of Cognitive Function in Older Adults by Clock Drawing, Box Copying and Narrative Writing
Paganini‐Hill, A., & Clark, L. J. (2006) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000097097 · Cited by 19
Cyclooxygenase I and II inhibitors distinctly enhance hippocampal- and cortex-dependent cognitive functions in mice
Syed, H., Ikram, M. F., Yaqinuddin, A., & Ahmed, T. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4351 · Cited by 19
Design, synthesis and preliminary biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen
Wu, X., Li, X., Mi, J., You, J., & Hai, L. (2013) · Chinese Chemical Letters · doi:10.1016/j.cclet.2013.01.022 · Cited by 19
Diacylglycerols as biomarkers of sustained immune activation in Proteinopathies associated with dementia
Wood, P. L., Cebak, J. E., & Woltjer, R. L. (2017) · Clinica Chimica Acta · doi:10.1016/j.cca.2017.11.009 · Cited by 20
Targeting cytokine expression in glial cells by cellular delivery of an NF-κB decoy
Fisher, L., Samuelsson, M., Jiang, Y., Ramberg, V., Figueroa, R., Hallberg, E., Langel, Ü., & Iverfeldt, K. (2007) · Journal of Molecular Neuroscience · doi:10.1385/jmn:31:03:209 · Cited by 19
“…31, 2007 although contradictory reports exist, several clinical and epidemiological studies have indicated that the incidence of AD decreases after long-term treatment with nonsteroidal anti-inflammatory drugs (Rogers et al., 1993; Breitner et al., 1995; in t’ Veld et al., 2001; Aisen, 2002).”
Background
Neuroimmune Pharmacology of Neurodegenerative and Mental Diseases
Shie, F., Chen, Y., Chen, C., & Ho, I.-K. (2010) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-010-9241-8 · Cited by 19
Disordered proteins in dementia
Ingelsson, M., & Hyman, B. T. (2002) · Annals of Medicine · doi:10.1080/078538902320322529 · Cited by 20
Dynamic regulation of microglial functions by the non-steroidal anti-inflammatory drug NCX 2216: Implications for chronic treatments of neurodegenerative diseases
Bernardo, A., Gasparini, L., Ongini, E., & Minghetti, L. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.09.012 · Cited by 19
“…the use of non-steroidal anti-inflammatory drugs (NSAIDs) for AD treatment was proposed in early 90s, on the basis of retrospective epidemiological studies showing that long-term treatment with these drugs reduces AD risk and slows its progression (McGeer and Rogers, 1992; in’t Veld et al., 2001).”
Background
Celecoxib effect on rivastigmine anti-Alzheimer activity against aluminum chloride-induced neurobehavioral deficits as a rat model of Alzheimer's disease; novel perspectives for an old drug
Abdel‐Aal, R. A., Hussein, O. A., Elsaady, R. G., & Abdelzaher, L. A. (2021) · Journal of Medical and Life Science · doi:10.21608/jmals.2021.210630 · Cited by 17
The Immune System as a Therapeutic Target for Alzheimer’s Disease
Zieneldien, T., Kim, J., Sawmiller, D. R., & Cao, C. (2022) · Life · doi:10.3390/life12091440 · Cited by 19
Involvement of inflammasomes in the pathogenesis of Alzheimer's disease
Beder, N., Belkhelfa, M., & Leklou, H. (2024) · Journal of Alzheimer s Disease · doi:10.1177/13872877241283677 · Cited by 20
New uses for old drugs: Novel therapeutic options
Verma, U., Sharma, R., Gupta, P., Kapoor, B., Bano, G., & Sawhney, V. (2005) · Indian Journal of Pharmacology · doi:10.4103/0253-7613.16850 · Cited by 18
Determining the Molecular Pathways Underlying the Protective Effect of Non-Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics Approach
Nevado‐Holgado, A. J., & Lovestone, S. (2016) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2016.10.003 · Cited by 17
“More recent observational studies have largely replicated this ﬁ nding [10 – 15], but to date there has been no translation of this observation into a usable therapy in randomised trials [16 – 18].”
BackgroundMethod
Modeling Alzheimer’s disease brains in vitro
Henstridge, C. M., & Spires‐Jones, T. L. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0177-2 · Cited by 19
Pathophysiological Role of TRPM2 in Age-Related Cognitive Impairment in Mice
Kakae, M., Miyanohara, J., Morishima, M., Nagayasu, K., Mori, Y., Shirakawa, H., & Kaneko, S. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.04.012 · Cited by 18
Selective modulation of amyloid‐β peptide degradation by flurbiprofen, fenofibrate, and related compounds regulates Aβ levels
Abdul‐Hay, S. O., Edirisinghe, P. D., & Thatcher, G. R. J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06355.x · Cited by 17
“Non-steroidal anti-inflammatory drugs and c-secretase modulators Epidemiological studies have shown that chronic NSAID treatment lowers the risk of AD (Rich et al. 1995; McGeer and McGeer 1996; Stewart et al. 1997; Mackenzie and Munoz 1998; in t’ Veld et al. 2001).”
Background
Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H β-synuclein
Sekiyama, K., Fujita, M., Sekigawa, A., Takamatsu, Y., Waragai, M., Takenouchi, T., Sugama, S., & Hashimoto, M. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.03.037 · Cited by 18
Is pharmacological prevention of Alzheimer's a realistic goal?
Anthony, J. C., Breitner, J. C. S., & Zandi, P. P. (2002) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.3.4.365 · Cited by 18
Effects of sulindac sulfide on the membrane architecture and the activity of γ-secretase
Gamerdinger, M., Clement, A. B., & Behl, C. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.02.009 · Cited by 18
“Epidemiological studies indicate that the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the prevalence of AD (in t’ Veld et al., 2001).”
Background
Novel phage peptides attenuate beta amyloid-42 catalysed hydrogen peroxide production and associated neurotoxicity
Taddei, K., Laws, S. M., Verdile, G., Munns, S. E., D'Costa, K. J., Harvey, A. R., Martins, I. J., Hill, F., Levy, E., Shaw, J. E., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.03.023 · Cited by 18
Thinking preventively about dementia: a review
Cooper, B. K. (2002) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.707 · Cited by 17
Strategies to Reduce the Risk of Cognitive Decline and Dementia
Andel, R., Hughes, T. F., & Crowe, M. G. (2005) · Aging Health · doi:10.2217/1745509x.1.1.107 · Cited by 18
The brain consequences of systemic inflammation were not fully alleviated by ibuprofen treatment in mice
Salmani, H., Hosseini, M., Baghcheghi, Y., & Noshahr, Z. S. (2020) · Pharmacological Reports · doi:10.1007/s43440-020-00141-y · Cited by 16
Brain-Derived Neurotrophic Factor Gene Variants and Alzheimer Disease: An Association Study in an Alzheimer Disease Italian Population
Boiocchi, C., Maggioli, E., Zorzetto, M., Sinforiani, E., Cereda, C., Ricevuti, G., & Cuccia, M. (2012) · Rejuvenation Research · doi:10.1089/rej.2012.1381 · Cited by 17
Roles of the prostaglandin E2 receptors EP subtypes in Alzheimer’s disease
Wei, L., Shen, Y., Zhang, Y., Hu, X., Lu, P.-L., Wang, L., & Chen, W. (2010) · Neuroscience Bulletin · doi:10.1007/s12264-010-0703-z · Cited by 17
“Epidemiological studies have demonstrated that long-term intake of nonsteroidal anti-inflammatory drugs (NSAIDs) during normal aging reduces the risk of AD and delays the onset of the disease[2-5].”
Background
Effects of ABCA1 R219K Polymorphism and Serum Lipid Profiles on Mild Cognitive Impairment in Type 2 Diabetes Mellitus
Cai, R., Han, J., Sun, J. L., Huang, R., Tian, S., Shen, Y., & Wang, S. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00257 · Cited by 17
Amyloids of multiple species: are they helpful in survival?
Upadhyay, A., & Mishra, A. (2018) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12399 · Cited by 17
Neuroimmune interactions in Alzheimer's disease—New frontier with old challenges?
Prokop, S., Lee, V. M. ‐., & Trojanowski, J. Q. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.10.002 · Cited by 17
Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in‐depth exploration of seven established risk factors
Peters, R. K., Breitner, J. C. S., James, S., Jicha, G. A., Meyer, P., Richards, M., Smith, A. D., Yassine, H. N., Abner, E. L., Hainsworth, A. H., et al. (2021) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12202 · Cited by 19
Ibuprofen Favors Binding of Amyloid-β Peptide to Its Depot, Serum Albumin
Андреевна, Л. Е., Kazakov, A. S., Deryusheva, E. I., Леонидовна, Н. Е., Shevelyova, M. P., Валериевич, М. А., Nazipova, A. A., Permyakova, M. E., Uversky, V. N., & Permyakov, S. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116168 · Cited by 19
Ibuprofen partially attenuates neurodegenerative symptoms in presenilin conditional double-knockout mice
Dong, Z. H., Li, Y., Huang, G. J., Zhang, L., Mei, B., & Meng, B. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.03.048 · Cited by 18
Isoindol-1,3-dione and isoindol-1-one derivatives with high binding affinity to β-amyloid fibrils
Lee, H. J., Lim, S. J., Oh, S. J., Moon, D. H., Kim, D. J., Tae, J., & Yoo, K. H. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.01.066 · Cited by 17
Multi factorial interactions in the pathogenesis pathway of Alzheimer’s disease: a new risk charts for prevention of dementia
Licastro, F., Porcellini, E., Forti, P., et al. (2010) · Immunity & Ageing · doi:10.1186/1742-4933-7-s1-s4 · Cited by 17
Potential Use of Nanomedicine for the Anti-inflammatory Treatment of Neurodegenerative Diseases
Otero, M. D. C., Espinosa‐Oliva, A. M., Herrera, A. J., García-Domínguez, I., Arévalo, M. F., Martín‐Banderas, L., & de Pablos, R. M. (2018) · Current Pharmaceutical Design · doi:10.2174/1381612824666180403113015 · Cited by 17
Lack of genetic association between PPARG gene polymorphisms and Finnish late-onset Alzheimer's disease
Helisalmi, S., Tarvainen, T., Vepsäläinen, S., Koivisto, A. M., Hiltunen, M. O., & Soininen, H. S. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.06.029 · Cited by 17
Treatment Strategies in Alzheimer???s Disease with a Focus on Early Pharmacological Interventions
Marksteiner, J., & Schmidt, R. (2004) · Drugs & Aging · doi:10.2165/00002512-200421070-00001 · Cited by 17
Facteurs de risque de la maladie d’Alzheimer: vers une prévention?
Vogel, T., Bénétos, A., Verreault, R., Kaltenbach, G., Kiesmann, M., & Berthel, M. (2006) · La Presse Médicale · doi:10.1016/s0755-4982(06)74810-2 · Cited by 19
Oxidative stress in a rat model of chronic gliosis
Bates, K. A., Martins, R. N., & Harvey, A. R. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.003 · Cited by 18
Vascular dementia
Desmond, D. W. (2004) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2004.04.009 · Cited by 17
Utilizing combination therapy in the treatment of Alzheimer’s disease
Farlow, M. R. (2004) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.4.5.799 · Cited by 17
Current Concepts in the Prevention of Alzheimer's Disease
Sano, M. (2003) · CNS Spectrums · doi:10.1017/s1092852900019283 · Cited by 17
Vessel‐encoded arterial spin labeling (VE‐ASL) reveals elevated flow territory asymmetry in older adults with substandard verbal memory performance
Donahue, M. J., Hussey, E. P., Levendovszky, S. R., Wilson, T., van Osch, M. J. P., Hartkamp, N. S., Hendrikse, J., & Ally, B. A. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24150 · Cited by 16
Ibuprofen Inhibits the Synaptic Failure Induced by the Amyloid-β Peptide in Hippocampal Neurons
Zurita, M. P., Muñoz, G., Sepúlveda, F. J., Gómez, P., Castillo, C., Burgos, C. F., Fuentealba, J., Opazo, C., & Aguayo, L. G. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122314 · Cited by 16
Ibuprofen Rescues Abnormalities in Periodontal Tissues in Conditional Presenilin 1 and Presenilin 2 Double Knockout Mice
Su, J., Gu, J., Dong, Z., & Mei, B. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140918457 · Cited by 16
Can the benefits of cannabinoid receptor stimulation on neuroinflammation, neurogenesis and memory during normal aging be useful in AD prevention?
Marchalant, Y., Baranger, K., Wenk, G. L., Khrestchatisky, M., & Rivera, S. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-10 · Cited by 16
Indomethacin Serves as a Potential Inhibitor of Protein Phosphatases
Kanno, T., Tsuchiya, A., Shimizu, T., et al. (2012) · Cellular Physiology and Biochemistry · doi:10.1159/000341478 · Cited by 16
From Small to Big Molecules: How Do We Prevent and Delay the Progression of Age-Related Neurodegeneration?
Ho, J. Y. S., Poon, D. C.-H., Chan, T. F., & Chang, R. C. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212798919039 · Cited by 16
Pharmacotherapy of Alzheimer’s Disease: Current State and Future Perspectives
Korábečný, J., Zemek, F., Soukup, O., Špilovská, K., Musílek, K., Jun, D., Nepovimová, E., & Kuča, K. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-803959-5.50001-5 · Cited by 18
Selective Cyclooxygenase-2 Inhibitors
Black, W. C. (2004) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(04)39010-x · Cited by 16
Alzheimer's Disease: Fatty Acids We Eat may be Linked to a Specific Protection via Low-dose Aspirin.
Pomponi, M. F. L., Gambassi, G., Pomponi, M., & Masullo, C. (2010) · Europe PMC (PubMed Central) · Cited by 15
The adverse renal effects of prostaglandin-synthesis inhibition in the fetus and the newborn
Drukker, A. (2002) · Paediatrics & Child Health · doi:10.1093/pch/7.8.538 · Cited by 16
Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans
Ling, I., Golde, T. E., Galasko, D. R., & Koo, E. H. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0137-y · Cited by 16
Cognitive Pharmacotherapy of Alzheimer's Disease and other Dementias
Herrmann, N. (2002) · The Canadian Journal of Psychiatry · doi:10.1177/070674370204700802 · Cited by 16
Anti-inflammatory activity of total alkaloids from Hypecoum leptocarpum hook. f. et Thoms
Shao, Y., Tao, Y., Wen, H., et al. (2018) · Pharmacognosy Magazine · doi:10.4103/pm.pm_139_17 · Cited by 16
Transglutaminase‐mediated crosslinking of neural proteins in Alzheimer's disease and other primary dementias
Sárvári, M., Fésüs, L., & Nemes, Z. (2002) · Drug Development Research · doi:10.1002/ddr.10098 · Cited by 60
“Nonsteroidal antiinflammatory drugs were shown to retard the onset and development of AD [In t’ Veld et al., 2001].”
Background
Hypothesis: cerebrospinal fluid protein markers suggest a pathway toward symptomatic resilience to AD pathology
Meyer, P., Savard, M., Poirier, J., Morgan, D., Breitner, J. C. S., & Initiative, A. D. N. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.05.007 · Cited by 15
“Early epidemiological studies showed an inverse association between anti-inflammatory drug use and AD risk [12,68].”
Background
Resolving inflammatory links between myocardial infarction and vascular dementia
Thorp, E. B., Flanagan, M. E., Popko, B., & DeBerge, M. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101600 · Cited by 17
Acute Myocardial Infarction and Proinflammatory Gene Variants
Licastro, F., CHIAPELLI, M., Caldarera, C. M., Caruso, C., Lio, D., & Corder, E. H. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1404.004 · Cited by 15
Placebo controlled phase II clinical trial: Safety and efficacy of combining intranasal insulin & acute exercise
Gwizdala, K. L., Ferguson, D. P., Kovan, J. R., Novak, V., & Pontifex, M. B. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00727-2 · Cited by 16
Bisindole compound 4ae ameliorated cognitive impairment in rats with vascular dementia by anti-inflammation effect via microglia cells
Zhang, F., Zhao, K., Tang, T., et al. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174357 · Cited by 15

Authors: in 't Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., Breteler, M. M. B., & Stricker, B. H. C.
Affiliations: Erasmus MC (NL)
National Institutes of Health (US)
ORCID: Launer, Lenore J.
Stijnen, Theo
Breteler, Monique M.B.
Stricker, Bruno H.C.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2001-11-22
Volume: 345
Issue: 21
Pages: 1515-1521
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa010178
OpenAlex: W2083556882
Semantic Scholar: 29c01ac52ec50618ec7b3b87ca55b707ca397434
Cited by: 1,196
References: 44
Citations by year: 2026: 13 · 2025: 14 · 2024: 18 · 2023: 23 · 2022: 26 · 2021: 33 · 2020: 23 · 2019: 40 · 2018: 38 · 2017: 28 · 2016: 40 · 2015: 49 · 2014: 49 · 2013: 39 · 2012: 50
FWCI: 52.61
Type: journal article
Language: en
Open access: green
pure.eur.nl
Licence: other-oa
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Keywords: nonsteroidal anti-inflammatory drugs, Alzheimer's disease, vascular dementia, dementia risk, long-term NSAID use, older adults
MeSH terms: Aged, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Prospective Studies, Risk, Salicylates, Dementia, Vascular, Cohort Studies, Proportional Hazards Models

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks