Treatment for Rheumatoid Arthritis and Risk of Alzheimer’s Disease: A Nested Case-Control Analysis
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Introduction It is increasingly becoming accepted that inflammation may play an important role in the pathogenesis of Alzheimer's disease (AD), as several immune-related genes have been associated with AD. Among these is tumor necrosis factor (TNF)-α, a proinflammatory cytokine known to play an important role in autoimmune disorders, including rheumatoid arthritis (RA). Although AD and RA appear to involve similar pathological mechanisms through the production of TNF-α, the relationship between AD and RA remains unknown.Objective To determine the relative risk of AD among RA patients and non-RA patients, and whether anti-TNF therapy for RA was associated with a lower risk of AD in RA patients.Methods We performed a nested case-control study of more than 8.5 million commercially insured adults (aged ≥18 years) in all 50 US states, Puerto Rico, and US Virgin Islands in the Verisk Health claims database. We derived a sub-cohort of subjects with a diagnosis of RA (controls), or RA and AD (cases), matching cases and controls based on age, sex, exposure assessment period, and methotrexate treatment. We also assessed relative risk of AD following exposure to standard RA therapies, including anti-TNF agents (infliximab, adalimumab, etanercept), methotrexate, prednisone, sulfasalazine, and rituximab. Odds ratios were adjusted for comorbidities, including coronary artery disease, diabetes mellitus, and peripheral vascular disease.Results AD was more prevalent (p < 0.0001) among RA patients (0.79 %) than among those without RA (0.11 %). Chronic conditions such as coronary artery disease (odds ratio [OR] 1.48; 95 % confidence interval [CI] 1.04-2.05; p = 0.03), diabetes (OR 1.86; 95 % CI 1.32-2.62; p = 0.0004), and peripheral vascular disease (OR 1.61; 95 % CI 1.06-2.43; p = 0.02) significantly increased the relative risk of AD among RA patients. Exposure to anti-TNF agents as a class, but not other immunosuppressive drugs studied, was associated with lowered risk of AD among RA patients (unadjusted OR 0.44; 95 % CI 0.22-0.87; p = 0.02; adjusted OR 0.45; 95 % CI 0.23-0.90; p = 0.02). Sub-group analysis demonstrated that of the three anti-TNF agents studied, only etanercept (unadjusted OR, 0.33; 95 % CI 0.08-0.94; p = 0.03; adjusted OR 0.30; 95 % CI 0.08-0.89; p = 0.02) was associated with a decreased risk of AD in RA patients.Conclusion There is an increased risk of AD in the studied RA population. The relative risk of AD among RA subjects was lowered in those exposed to etanercept. Anti-TNF therapy with etanercept shows promise as a potential treatment for AD.
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The risk of developing Alzheimer's disease was significantly lower among patients with rheumatoid arthritis treated with the TNF-α inhibitor etanercept.
“The risk for developing Alzheimer’s disease was also significantly lower among patients with rheumatoid arthritis treated with the TNF-α inhibitor etanercept43.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [43]
In one study, rheumatoid arthritis patients treated with etanercept had lower incidence of Alzheimer disease, but no effect was noted with other anti-rheumatic medications or anti-TNF agents.
“In one study, patients with rheumatoid arthritis treated with etanercept, TNFα decoy receptor, had lower incidence of AD, but no effect was noted with use of other anti-rheumatic medications (prednisone, sulfasalazine, rituximab) or anti-TNF agents (infliximab, adalimumab) (Chou et al., 2016).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Chou et al., 2016
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McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · see citing works
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155 · see citing works
The Pathogenesis of Rheumatoid Arthritis
McInnes, I. B., & Schett, G. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1004965 · Cited by 5,514 · see citing works
Lawrence, R. C., Felson, D. T., Helmick, C. G., Arnold, L. M., Choi, H. K., Deyo, R. A., Gabriel, S. E., Hirsch, R., Hochberg, M. C., Hunder, G. G., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.23176 · Cited by 5,500 · see citing works
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069 · see citing works
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336 · see citing works
Targan, S. R., Hanauer, S. B., van Deventer, S. J. H., Mayer, L., Present, D. H., Braakman, T., DeWoody, K. L., Schaible, T. F., & Rutgeerts, P. J. (1997) · New England Journal of Medicine · doi:10.1056/nejm199710093371502 · Cited by 3,135 · see citing works
Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125 · see citing works
Alzheimer disease in the United States (2010–2050) estimated using the 2010 census
Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013) · Neurology · doi:10.1212/wnl.0b013e31828726f5 · Cited by 2,642 · see citing works
Albert, M., DeKosky, S. T., Dickson, D. W., Dubois, B., Feldman, H., Fox, N. C., Gamst, A. C., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2013) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.11.1.96 · Cited by 2,630 · see citing works
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part I
Helmick, C. G., Felson, D. T., Lawrence, R. C., Gabriel, S. E., Hirsch, R., Kwoh, C. K., Liang, M. H., Kremers, H. M., Mayes, M. D., Merkel, P. A., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.23177 · Cited by 2,054 · see citing works
2015 Alzheimer's disease facts and figures
Alzheimer's Association (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.02.003 · Cited by 1,641 · see citing works
An english translation of alzheimer’s 1907 paper, “über eine eigenartige erkankung der hirnrinde”
Stelzmann, R. A., Norman Schnitzlein, H., & Reed Murtagh, F. (1995) · Clinical Anatomy · doi:10.1002/ca.980080612 · Cited by 1,455 · see citing works
Falk, R. H., Comenzo, R. L., & Skinner, M. (1997) · New England Journal of Medicine · doi:10.1056/nejm199709253371306 · Cited by 1,185 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Evidence that cytokines play a role in rheumatoid arthritis
Brennan, F. M., & McInnes, I. B. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36389 · Cited by 1,103 · see citing works
Epidemiology of Alzheimer DiseasePreprint
Mayeux, R. P., & Stern, Y. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006239 · Cited by 1,070 · see citing works
Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins
Ray, S., Britschgi, M., Herbert, C., Takeda-Uchimura, Y., Boxer, A., Blennow, K., Friedman, L. F., Galasko, D. R., Jutel, M., Karydas, A., et al. (2007) · Nature Medicine · doi:10.1038/nm1653 · Cited by 1,048 · see citing works
Etanercept plus Standard Therapy for Wegener's Granulomatosis
The Wegener's Granulomatosis Etanercept Trial Research Group (2005) · New England Journal of Medicine · doi:10.1056/nejmoa041884 · Cited by 829 · see citing works
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · see citing works
Lombardo, I., Ramaswamy, G., Piscitelli, S. C., & Friedhoff, L. T. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.08.154 · Cited by 656 · see citing works
Cytokines in rheumatoid arthritis — shaping the immunological landscape
McInnes, I. B., Buckley, C. D., & Isaacs, J. D. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.171 · Cited by 504 · see citing works
Intrathecal inflammation precedes development of Alzheimer's disease
Tarkowski, E. (2003) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.9.1200 · Cited by 501 · see citing works
Diabetes, Alzheimer disease, and vascular dementia
Ahtiluoto, S., Polvikoski, T. M., Peltonen, M., Solomon, A., Tuomilehto, J., Winblad, B. G., Sulkava, R. O., & Kivipelto, M. (2010) · Neurology · doi:10.1212/wnl.0b013e3181f4d7f8 · Cited by 493 · see citing works
The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis
Tobón, G. J., Youinou, P., & Saraux, A. (2010) · Journal of Autoimmunity · doi:10.1016/j.jaut.2009.12.009 · Cited by 485 · see citing works
Baert, F. J., D’Haens, G., Peeters, M., Hiele, M. I., Schaible, T. F., Shealy, D. J., Geboes, K. J., & Rutgeerts, P. J. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70224-6 · Cited by 460 · see citing works
Brosseron, F., Krauthausen, M., Kummer, M., & Heneka, M. T. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8657-1 · Cited by 447 · see citing works
The epidemiology of the dementias: an update
Qiu, C., Ronchi, D. D., & Fratiglioni, L. (2007) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32816ebc7b · Cited by 418 · see citing works
Tarkowski, E., Blennow, K., Wallin, A., & Tarkowski, A. (1999) · Journal of Clinical Immunology · doi:10.1023/a:1020568013953 · Cited by 349 · see citing works
Evidence that Aβ42 is the real culprit in alzheimer's disease
Younkin, S. G. (1995) · Annals of Neurology · doi:10.1002/ana.410370303 · Cited by 331 · see citing works
Alzheimer's Aβ42 and Aβ40 peptides form interlaced amyloid fibrils
Gu, L., & Guo, Z. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12202 · Cited by 325 · see citing works
Kaymakcalan, Z., Sakorafas, P., Bose, S., Scesney, S. M., Xiong, L., Hanzatian, D. K., Salfeld, J. G., & Sasso, E. H. (2009) · Clinical Immunology · doi:10.1016/j.clim.2009.01.002 · Cited by 317 · see citing works
State-of-the-art: rheumatoid arthritis
McInnes, I. B., & O’Dell, J. R. (2010) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2010.134684 · Cited by 304 · see citing works
Why Match? Investigating Matched Case-Control Study Designs with Causal Effect Estimation
Rose, S., & van der Laan, M. J. (2009) · The International Journal of Biostatistics · doi:10.2202/1557-4679.1127 · Cited by 293 · see citing works
Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis
Bernatsky, S., Hudson, M., & Suissa, S. (2007) · Lara D. Veeken · doi:10.1093/rheumatology/kem076 · Cited by 281 · see citing works
AA Amyloidosis: Pathogenesis and Targeted Therapy
Westermark, G. T., Fändrich, M., & Westermark, P. (2014) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163913 · Cited by 265 · see citing works
Etanercept in Alzheimer disease
Butchart, J., Brook, L., Hopkins, V., Teeling, J. L., Püntener, U., Culliford, D. J., Sharples, R., Sharif, S., McFarlane, B., Raybould, R., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001617 · Cited by 249 · see citing works
Mattsson, N., Tosun, D., Insel, P. S., Simonson, A., Jack, C. R., Beckett, L. A., Donohue, M., Jagust, W., Schuff, N. W., & Weiner, M. W. (2014) · Brain · doi:10.1093/brain/awu043 · Cited by 211 · see citing works
Tetta, C., Camussi, G., Modena, V., Vittorio, C. D., & Baglioni, C. (1990) · Annals of the Rheumatic Diseases · doi:10.1136/ard.49.9.665 · Cited by 205 · see citing works
Tweedie, D., Sambamurti, K., & Greig, N. H. (2007) · Current Alzheimer Research · doi:10.2174/156720507781788873 · Cited by 188 · see citing works
Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis
Centola, M. B., Cavet, G., Shen, Y., Ramanujan, S., Knowlton, N. S., Swan, K. A., Turner, M. S., Sutton, C., Smith, D. R., Haney, D. J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060635 · Cited by 186 · see citing works
Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers
Beeri, M. S., Rapp, M. A., Silverman, J. M., Schmeidler, J., Grossman, H. T., Fallon, J. T., Purohit, D. P., Perl, D. P., Siddiqui, A., Lesser, G. T., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000210447.19748.0b · Cited by 129 · see citing works
Anti-TNF- therapies: they are all the same (aren't they?)
Mpofu, S. (2004) · British journal of rheumatology · doi:10.1093/rheumatology/keh483 · Cited by 102 · see citing works
Cognitive impairment in rheumatoid arthritis
Appenzeller, S., Bertolo, M. B., & Costallat, L. T. L. (2004) · Methods and Findings in Experimental and Clinical Pharmacology · doi:10.1358/mf.2004.26.5.831324 · Cited by 93 · see citing works
Amyloid precursors and amyloidosis in inflammatory arthritis.
Cunnane, G. (2001) · Current Opinion in Rheumatology · doi:10.1097/00002281-200101000-00011 · Cited by 80 · see citing works
Current state of tumour necrosis factor α blockade in Wegener's granulomatosis
Mukhtyar, C. B., & Luqmani, R. A. (2005) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2005.042416 · Cited by 60 · see citing works
Chen, Y., Chen, H., Lan, J.-L., & Chen, D. (2010) · Joint Bone Spine · doi:10.1016/j.jbspin.2010.01.017 · Cited by 31 · see citing works
Corrao, G., Zambon, A., Faini, S., Bagnardi, V., Leoni, O., & Suissa, S. (2005) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2004.04.013 · Cited by 25 · see citing works
Perspective: In search of biomarkers
Buckholtz, N. S. (2011) · Nature · doi:10.1038/475s8a · Cited by 24 · see citing works
Lack of association between TNF-α polymorphisms and Alzheimer’s disease in an Italian cohort
Tedde, A., Putignano, A. L., Nacmias, B., Bagnoli, S., Cellini, E., & Sorbi, S. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.09.044 · Cited by 19 · see citing works
(1889) · Journal of Mental Science · doi:10.1192/bjp.35.150.261 · Cited by 7 · see citing works
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Chronic inflammation in the etiology of disease across the life span
Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0675-0 · Cited by 4,915 · see citing works
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Macrophages in health and disease
Park, M. D., Silvin, A., Ginhoux, F., & Merad, M. (2022) · Cell · doi:10.1016/j.cell.2022.10.007 · Cited by 644 · see citing works
Lai, K. S. P., Liu, C. S., Rau, A., Lanctôt, K. L., Köhler, C. A., Pakosh, M., Carvalho, A. F., & Herrmann, N. (2017) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2017-316201 · Cited by 433 · see citing works
Webers, A., Heneka, M. T., & Gleeson, P. A. (2019) · Immunology and Cell Biology · doi:10.1111/imcb.12301 · Cited by 371 · see citing works
Silvin, A., Uderhardt, S., Piot, C., Da Mesquita, S., Yang, K., Geirsdottir, L., Mulder, K., Eyal, D., Liu, Z., Bridlance, C., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.07.004 · Cited by 368 · see citing works
The role of astroglia in Alzheimer's disease: pathophysiology and clinical implications
Arranz, A. M., & Strooper, B. D. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30490-3 · Cited by 349 · see citing works
Koźmiński, P., Halik, P. K., Chesori, R., & Gniazdowska, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103483 · Cited by 326 · see citing works
Systemic inflammation after stroke: implications for post‐stroke comorbidities
Simats, A., & Liesz, A. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216269 · Cited by 276 · see citing works
Targeting neuroinflammation in Alzheimer’s disease: from mechanisms to clinical applications
Si, Z.-Z., Zou, C.-J., Mei, X., Mei, X., Luo, H., Shen, Y., Hu, J., Li, X.-X., Wu, L., & Liu, Y. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.353484 · Cited by 192 · see citing works
Depression, dementia and immune dysregulation
Hayley, S., Hakim, A. M., & Albert, P. R. (2021) · Brain · doi:10.1093/brain/awaa405 · Cited by 186 · see citing works
Zhou, M., Xu, R., Kaelber, D. C., & Gurney, M. E. (2020) · PLOS ONE · doi:10.1371/journal.pone.0229819 · Cited by 157 · see citing works
A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis
Schrepf, A., Kaplan, C. M., Ichesco, E., Larkin, T. E., Harte, S. E., Harris, R. E., Murray, A. D., Waiter, G. D., Clauw, D. J., & Basu, N. (2018) · Nature Communications · doi:10.1038/s41467-018-04648-0 · Cited by 142 · see citing works
Steeland, S., Libert, C., & Vandenbroucke, R. E. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051442 · Cited by 137 · see citing works
Impact of the treatment of periodontitis on systemic health and quality of life: A systematic review
Orlandi, M., Aguilera, E. M., Marletta, D., Petrie, A., Suvan, J. E., & D’Aiuto, F. (2021) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.13554 · Cited by 135 · see citing works
Therapeutic Potential of TNF-α Inhibition for Alzheimer’s Disease Prevention
Torres-Acosta, N., O’Keefe, J. H., O’Keefe, E. L., Isaacson, R., & Small, G. W. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200711 · Cited by 129 · see citing works
Clark, I. A., & Vissel, B. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0708-2 · Cited by 123 · see citing works
Counteracting the effects of TNF receptor‐1 has therapeutic potential in Alzheimer's disease
Steeland, S., Gorlé, N., Vandendriessche, C., Balusu, S., Brkić, M., Cauwenberghe, C. V., Imschoot, G. V., Wonterghem, E. V., Rycke, R. M. D., Kremer, A., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708300 · Cited by 119 · see citing works
The Role of TNF-α in Alzheimer’s Disease: A Narrative Review
Plantone, D., Pardini, M., Righi, D., Manco, C., Colombo, B. M., & Stefano, N. D. (2023) · Cells · doi:10.3390/cells13010054 · Cited by 119 · see citing works
TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond
Siegmund, D., & Wajant, H. (2023) · Nature Reviews Rheumatology · doi:10.1038/s41584-023-01002-7 · Cited by 118 · see citing works
The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap
Walker, K. A., Page, L. M. L., Terrando, N., Duggan, M. R., Heneka, M. T., & Bettcher, B. M. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00627-2 · Cited by 118 · see citing works
Systemic and CNS Inflammation Crosstalk: Implications for Alzheimer’s Disease
Paouri, E., & Georgopoulos, S. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321154618 · Cited by 108 · see citing works
Temporal bias in case-control design: preventing reliable predictions of the future
Yuan, W., Beaulieu‐Jones, B. K., Yu, K., Lipnick, S., Palmer, N., Loscalzo, J., Cai, T., & Kohane, I. S. (2021) · Nature Communications · doi:10.1038/s41467-021-21390-2 · Cited by 84 · see citing works
Süß, P., Hoffmann, A., Rothe, T., Ouyang, Z., Baum, W., Staszewski, O., Schett, G. A., Prinz, M., Krönke, G., Glass, C. K., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.02.109 · Cited by 81 · see citing works
Yanuck, S. F. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00712 · Cited by 80 · see citing works
The meteorology of cytokine storms, and the clinical usefulness of this knowledge
Clark, I. A., & Vissel, B. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0628-y · Cited by 77 · see citing works
Cooper, J., Pastorello, Y., & SLEVIN, M. A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1087571 · Cited by 76 · see citing works
Paouri, E., Tzara, O., Kartalou, G.-I., Zenelak, S., & Georgopoulos, S. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2484-16.2017 · Cited by 76 · see citing works
Korologou-Linden, R., Bhatta, L., Brumpton, B. M., Howe, L. D., Millard, L. A. C., Kolaric, K., Ben-Shlomo, Y., Williams, D. M., Smith, G. D., Anderson, E. L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32183-6 · Cited by 71 · see citing works
Hay, M., Polt, R. L., Heien, M. L., Vanderah, T. W., Largent‐Milnes, T. M., Rodgers, K. E., Falk, T., Bartlett, M. J., Doyle, K. P., & Konhilas, J. P. (2019) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.254854 · Cited by 71 · see citing works
Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer’s Disease
Mishra, A., & Brinton, R. D. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00312 · Cited by 69 · see citing works
Süß, P., Rothe, T., Hoffmann, A., Schlachetzki, J. C. M., & Winkler, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.612104 · Cited by 69 · see citing works
Paouri, E., Tzara, O., Zenelak, S., & Georgopoulos, S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170065 · Cited by 60 · see citing works
Pagoni, P., Korologou‐Linden, R., Howe, L. D., Smith, G. D., Ben‐Shlomo, Y., Stergiakouli, E., & Anderson, E. L. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.05.006 · Cited by 60 · see citing works
Inflammation and dementia: Using rheumatoid arthritis as a model to develop treatments?
Mason, A., Holmes, C., & Edwards, C. J. (2018) · Autoimmunity Reviews · doi:10.1016/j.autrev.2018.04.001 · Cited by 59 · see citing works
Tang, Z., Liang, D., Cheng, M., Su, X., Liu, R., Zhang, Y., & Wu, H. (2020) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01629-1 · Cited by 53 · see citing works
Chronic peripheral inflammation: a possible contributor to neurodegenerative diseases
Süβ, P., Lana, A. J., & Schlachetzki, J. C. M. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.306060 · Cited by 54 · see citing works
Neuroimaging and biomarker evidence of neurodegeneration in asthma
Rosenkranz, M. A., Dean, D., Bendlin, B. B., Jarjour, N. N., Esnault, S. J., Zetterberg, H., Heslegrave, A., Evans, M. D., Davidson, R. J., & Busse, W. W. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.09.010 · Cited by 51 · see citing works
Biomarkers of non-communicable chronic disease: an update on contemporary methods
Al‐Hadlaq, S. M., Balto, H. A. G., Hassan, W. M., Marraiki, N., & El-Ansary, A. K. (2022) · PeerJ · doi:10.7717/peerj.12977 · Cited by 50 · see citing works
TNF alpha inhibitors in Alzheimer's disease: A systematic review
Ekert, J. O., Gould, R. L., Reynolds, G., & Howard, R. J. (2018) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4871 · Cited by 50 · see citing works
Sood, A., & Raji, M. A. (2020) · Clinical Rheumatology · doi:10.1007/s10067-020-05372-1 · Cited by 49 · see citing works
Neuroimmune Activation Drives Multiple Brain States
Tchessalova, D., Posillico, C. K., & Tronson, N. C. (2018) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2018.00039 · Cited by 46 · see citing works
Stefanovski, L., Meier, J. M., Pai, R. K., Triebkorn, P., Lett, T. A. P., Martin, L., Bülau, K., Hofmann‐Apitius, M., Solodkin, A., McIntosh, A. R., et al. (2021) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2021.630172 · Cited by 46 · see citing works
Desai, R. J., Varma, V. R., Gerhard, T., Segal, J., Mahesri, M., Chin, K., Horton, D. B., Kim, S. C., Schneeweiss, S., & Thambisetty, M. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.6567 · Cited by 45 · see citing works
Blood inflammation relates to neuroinflammation and survival in frontotemporal lobar degeneration
Malpetti, M., Swann, P., Tsvetanov, K. A., Chouliaras, L., Strauss, A., Chikaura, T., Murley, A. G., Ashton, N. J., Barker, P. B., Jones, P. S., et al. (2024) · Brain · doi:10.1093/brain/awae269 · Cited by 45 · see citing works
Li, R., Wang, J., Xiong, W., Luo, Y., Feng, H., Zhou, H., Peng, Y., He, Y., & Ye, Q. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1358179 · Cited by 44 · see citing works
Polygenic analysis of inflammatory disease variants and effects on microglia in the aging brain
Felsky, D., Patrick, E., Schneider, J. A., Mostafavi, S., Gaiteri, C., Patsopoulos, N. A., Bennett, D. A., & Jager, P. L. D. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0272-6 · Cited by 44 · see citing works
Targeting innate immunity to protect and cure Alzheimer’s disease: opportunities and pitfalls
Cisbani, G., & Rivest, S. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01083-4 · Cited by 43 · see citing works
Clark, I. A., & Vissel, B. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14471 · Cited by 42 · see citing works
Yli-Karjanmaa, M., Larsen, K. S., Fenger, C., Kristensen, L. K., Martin, N. A., Jensen, P. T., Breton, A., Nathanson, L., Nielsen, P. V., Lund, M. C., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.08.195 · Cited by 41 · see citing works
Lindbohm, J. V., Mars, N., Sipilä, P. N., Singh‐Manoux, A., Runz, H., FinnGen, Livingston, G., Seshadri, S. S., Xavier, R. J., Hingorani, A. D., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00293-x · Cited by 40 · see citing works
Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study
McDowell, B., Marr, C., Holmes, C., Edwards, C. J., Cardwell, C. R., McHenry, M., Meenagh, G., & McGuinness, B. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-04417-w · Cited by 39 · see citing works
Immune modulation to treat Alzheimer’s disease
Duggan, M. R., Morgan, D., Price, B. R., Rajbanshi, B., Martín‐Peña, A., Tansey, M. G., & Walker, K. A. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00828-x · Cited by 39 · see citing works
Yang, K., Lauritzen, K. H., Olsen, M. B., Dahl, T. B., Ranheim, T., Ahmed, M. S., Attramadal, H., Aukrust, P., Halvorsen, B. L., Nyman, T. A., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801382 · Cited by 39 · see citing works
Pharmacological Interventions to Attenuate Alzheimer’s Disease Progression: The Story So Far
Bazzari, F. H., Abdallah, D. M., & El-Abhar, H. S. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190301111120 · Cited by 38 · see citing works
LMP2 Inhibitors as a Potential Treatment for Alzheimer’s Disease
Bhattarai, D., Lee, M. J., Baek, A., Yeo, I. J., Miller, Z. C., Baek, Y. M., Lee, S., Kim, D., Hong, J. T., & Kim, K. B. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00416 · Cited by 36 · see citing works
Association of autoimmune diseases with Alzheimer's disease: A mendelian randomization study
Yeung, C. H. C., Yeung, S. L. A., & Schooling, C. M. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.09.052 · Cited by 36 · see citing works
Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex
Bottero, V., Powers, D., Yalamanchi, A., Quinn, J. P., & Potashkin, J. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083915 · Cited by 35 · see citing works
Gerring, Z. F., Gamazon, E. R., White, A. R., & Derks, E. M. (2021) · Neurology Genetics · doi:10.1212/nxg.0000000000000622 · Cited by 35 · see citing works
Doroszkiewicz, J., Mroczko, J., Winkel, I., & Mroczko, B. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13175057 · Cited by 34 · see citing works
Astrocyte subtype-specific approach to Alzheimer's disease treatment
Sarkar, S., & Biswas, S. C. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104956 · Cited by 34 · see citing works
Arbo, B. D., Schimith, L. E., dos Santos, M. G., & Hort, M. A. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174800 · Cited by 33 · see citing works
Alzheimer’s Disease and Rheumatoid Arthritis: A Mendelian Randomization Study
Cai, Q., Xin, Z., Zuo, L., Li, F., & Liu, B. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00627 · Cited by 31 · see citing works
The influence of physiological and pathological perturbations on blood-brain barrier function
Zhao, N., Chung, T. D., Guo, Z., Jamieson, J. J., Liang, L. R., Linville, R. M., Pessell, A. F., Wang, L., & Searson, P. C. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1289894 · Cited by 30 · see citing works
Li, Y., Fan, H., Ni, M., Zhang, W., Fang, F., Sun, J., Lyu, P., & Ma, P. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.11.001 · Cited by 30 · see citing works
Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline
Nair, A. K., Hulle, C. A. V., Bendlin, B. B., Zetterberg, H., Blennow, K., Wild, N., Kollmorgen, G., Suridjan, I., Busse, W. W., & Rosenkranz, M. A. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12315 · Cited by 30 · see citing works
Watad, ., McGonagle, D., Anis, S., Carmeli, R., Cohen, A. D., Tsur, A. M., Ben‐Shabat, N., Bragazzi, N. L., Lidar, M., & Amital, H. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106325 · Cited by 29 · see citing works
Yeo, I. J., Lee, M. J., Baek, A., Miller, Z. C., Bhattarai, D., Baek, Y. M., Jeong, H. J., Kim, Y. K., Kim, D., Hong, J. T., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54846-z · Cited by 29 · see citing works
Lai, P.-H., Wang, T.-H., Zhang, N.-Y., Wu, K.-C., Yao, C. J., & Lin, C. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02086-2 · Cited by 28 · see citing works
Macdonald, D. W., Berdoy, M., & Webster, J. P. (2015) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780198745501.003.0011 · Cited by 27 · see citing works
Resolution of inflammation: Intervention strategies and future applications
Panezai, J., & Dyke, T. E. V. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116089 · Cited by 27 · see citing works
Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond
Garmendia, J. V., Sanctis, C. V. D., Das, V., Annadurai, N., Hajdúch, M., & Sanctis, J. B. D. (2023) · Current Neuropharmacology · doi:10.2174/1570159x22666231017141636 · Cited by 27 · see citing works
Myasoedova, E., Sattui, S. E., Lee, J., O'Brien, J. T., & Makris, U. E. (2024) · The Lancet Rheumatology · doi:10.1016/s2665-9913(24)00190-5 · Cited by 27 · see citing works
Culibrk, R. A., & Hahn, M. S. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.583884 · Cited by 27 · see citing works
Clark, I., & Vissel, B. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201186 · Cited by 27 · see citing works
Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease
Fülöp, T., Tripathi, S., Rodrigues, S., Desroches, M., Bunt, T., Eiser, A. R., Bernier, F., Beauregard, P. B., Barron, A. E., Khalil, A., et al. (2021) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s264910 · Cited by 27 · see citing works
Zheng, C., Fillmore, N. R., Ramos‐Cejudo, J., Brophy, M. T., Osorio, R. S., Gurney, M. E., Qiu, W. Q., Au, R., Perry, G. L., Dubreuil, M., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12465 · Cited by 27 · see citing works
Desai, R. J., Varma, V. R., Gerhard, T., Segal, J. B., Mahesri, M., Chin, K., Nonnenmacher, E., Gabbeta, A., Oommen, A. M., Varma, S., et al. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12095 · Cited by 26 · see citing works
Sattui, S. E., Navarro-Millán, I. Y., Xie, F., Rajan, M., Yun, H., & Curtis, J. R. (2022) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2022.152083 · Cited by 26 · see citing works
Polyamine Dysregulation and Nucleolar Disruption in Alzheimer’s Disease
Brooks, W. H. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231184 · Cited by 24 · see citing works
Common Factors of Alzheimer’s Disease and Rheumatoid Arthritis—Pathomechanism and Treatment
Trzeciak, P., Herbet, M., & Dudka, J. (2021) · Molecules · doi:10.3390/molecules26196038 · Cited by 24 · see citing works
Detection of molecular signatures and pathways shared by Alzheimer’s disease and type 2 diabetes
Shu, J., Li, N., Wei, W., & Zhang, L. (2021) · Gene · doi:10.1016/j.gene.2021.146070 · Cited by 23 · see citing works
Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer’s Disease
Lee, M. J., Bhattarai, D., Jang, H., Baek, A., Yeo, I. J., Lee, S., Miller, Z. C., Lee, S., Hong, J. T., Kim, D., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00291 · Cited by 22 · see citing works
MLKL deficiency protects against low-grade, sterile inflammation in aged mice
Crutchfield, E. C. T., Garnish, S. E., Day, J. A., Anderton, H., Chiou, S., Hempel, A., Hall, C. M., Patel, K. M., Gangatirkar, P., Martin, K., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01121-4 · Cited by 22 · see citing works
Peripheral inflammation is a potential etiological factor in Alzheimer’s disease
Li, Z., Wang, H., & Yin, Y. (2023) · Reviews in the Neurosciences · doi:10.1515/revneuro-2023-0049 · Cited by 22 · see citing works
Ritson, M., Wheeler-Jones, C. P. D., & Stolp, H. B. (2024) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2024.578363 · Cited by 23 · see citing works
McGuinness, B., Holmes, C., Mirakhur, A., Kearsley‐Fleet, L., Vieira, R., Watson, K. D., BSRBR‐RA Contributors Group, & Hyrich, K. L. (2018) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4793 · Cited by 22 · see citing works
Khan, H., Naseem, T., Kaushik, P., Narang, J., Khan, R., Panwar, S., & Parvez, S. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102535 · Cited by 21 · see citing works
Müller, S., van Oosterhout, A., Bervoets, C., Christen, M., Martínez-Álvarez, R., & Bittlinger, M. (2022) · Neuroethics · doi:10.1007/s12152-022-09485-z · Cited by 20 · see citing works
Sattui, S. E., Rajan, M., Lieber, S. B., Lui, G. E., Sterling, M. R., Curtis, J. R., Mandl, L. A., & Navarro-Millán, I. Y. (2021) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2020.09.022 · Cited by 20 · see citing works
Shorey, C. L., Mulla, R. T., & Mielke, J. G. (2022) · Brain Research · doi:10.1016/j.brainres.2022.148157 · Cited by 19 · see citing works
Gwinnutt, J. M., Toyoda, T., Barraclough, M. L., Verstappen, S. M. M., Hornberger, M., & MacGregor, A. J. (2022) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2022.152131 · Cited by 19 · see citing works
Rheumatoid Arthritis and Cognitive Impairment or Dementia: An Updated Review of Epidemiological Data
Sharma, S. R., & Chen, Y. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230234 · Cited by 19 · see citing works
Aries, M. L., Cook, M., & Hensley‐McBain, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105357 · Cited by 19 · see citing works
Guo, X., Li, M., Li, S., Liu, F., Liu, Z., & Yang, P. (2017) · Cell Biochemistry and Function · doi:10.1002/cbf.3250 · Cited by 18 · see citing works
Booth, M. J., Janevic, M. R., Kobayashi, L. C., Clauw, D. J., & Piette, J. D. (2021) · BMC Rheumatology · doi:10.1186/s41927-021-00198-z · Cited by 18 · see citing works
Executable pathway analysis using ensemble discrete-state modeling for large-scale data
Palli, R., Palshikar, M. G., & Thakar, J. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007317 · Cited by 18 · see citing works
Xie, W., Hou, Y., Xiao, S., Zhang, X., & Zhang, Z. (2024) · RMD Open · doi:10.1136/rmdopen-2023-004016 · Cited by 17 · see citing works
Vassilaki, M. E., Crowson, C. S., Davis, J. M., Duong, S. Q., Jones, D. T., Nguyen, A. T., Mielke, M. M., Vemuri, P., & Myasoedova, E. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220368 · Cited by 16 · see citing works
Kalovyrna, N., Apokotou, O., Boulekou, S., Paouri, E., Boutou, A., & Georgopoulos, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-65378-2 · Cited by 16 · see citing works
- Authors
- Chou, R. C., Kane, M., Ghimire, S., Gautam, S., & Gui, J.
- Affiliations
- Dartmouth College (US)
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Chou, Richard C.
- ORCID
- Gui, Jiang
- Venue
- CNS Drugs
- Published
- 2016-07-28
- Volume
- 30
- Issue
- 11
- Pages
- 1111-1120
- ISSN
- 1172-7047 (ISSN-L)
- 1179-1934
- PMC
- PMC5585782
- OpenAlex
- W2489613804
- Cited by
- 194
- References
- 53
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 17 · 2023: 24 · 2022: 33 · 2021: 27 · 2020: 23 · 2019: 21 · 2018: 12 · 2017: 6 · 2016: 1 · 2015: 1 · 2012: 1
- FWCI
- 14.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA023108)
- U.S. National Library of Medicine (R01LM012012)
- National Center for Research Resources (UL1RR025758)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- rheumatoid arthritis, Alzheimer's disease, anti-TNF therapy, TNF-α, inflammation, methotrexate, infliximab, adalimumab, etanercept, rituximab, sulfasalazine, prednisone, comorbidities, coronary artery disease, diabetes mellitus, peripheral vascular disease, immunosuppressants
- MeSH terms
- Adult, Aged, Alzheimer Disease, Arthritis, Rheumatoid, Female, Humans, Male, Middle Aged, Risk, Tumor Necrosis Factor-alpha, Cohort Studies, Case-Control Studies, Antirheumatic Agents
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