Association between Atopic Dermatitis and Dementia: Evidence from Systematic Review, Meta-analysis, and Mendelian Randomization

Authors

  • Yeon-Su Gwak School of Medicine, Pusan National University, Yangsan, Republic of Korea
  • Seo-Yeon Kim School of Medicine, Pusan National University, Yangsan, Republic of Korea
  • Chae-Eon Woo School of Medicine, Pusan National University, Yangsan, Republic of Korea
  • Kihyuk Shin Department of Dermatology, College of Medicine, Pusan National University, Busan, Korea; Department of Dermatology, Pusan National University Yangsan Hospital, Yangsan, Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Busan, Korea
  • Eunjeong Son Division of Respiratory and Allergy, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
  • Jin-Woo Kim Department of Oral and Maxillofacial Surgery, Research Institute for Intractable Osteonecrosis of the Jaw, Ewha Womans University College of Medicine, Seoul, Republic of Korea
  • Sung-Jin Kim Department of Oral Histology and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea
  • Tae-Jin Song Department of Neurology, Seoul Hospital, Ewha Womans University College of Medicine, Republic of Korea
  • Hae Ryoun Park Department of Periodontology and Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Republic of Korea; Periodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan, Republic of Korea; Department of Oral Pathology, Dental and Life Science Institute, Pusan National University, Yangsan, Republic of Korea
  • Kihun Kim Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea
  • Dai Sik Ko Division of Vascular Surgery, Department of General Surgery, Gachon University College of Medicine, Gil Medical Center, Incheon, Republic of Korea
  • Yun Hak Kim Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea

DOI:

https://doi.org/10.2340/actadv.v105.41321

Keywords:

atopic dermatitis, dementia, Alzheimer's disease, systematic review, meta-analysis, Mendelian randomization

Abstract

Recent cohort studies suggest a potential association between atopic dermatitis and dementia, though the evidence remains conflicting. This study aims to elucidate the association between atopic dermatitis and dementia employing systematic review, meta-analysis, and Mendelian randomization (MR). A comprehensive search was performed to select eligible cohort studies using Medline, Embase, Scopus, ScienceDirect, and the Web of Science database. In MR analysis, genomic data from the Genome Wide Association Study (GWAS) (864,982 European individuals) for atopic dermatitis cases and dementia cases were obtained from the MRBase. Statistical analyses included the inverse-variance weighted (IVW) method, sensitivity tests, and MR-PRESSO for outliers. The adjustment accounted for various factors, including sex, age, smoking status, and other medical comorbidities, along with several additional variables. In the systematic review and meta-analysis, 5 longitudinal cohort studies (12,576,235 participants) indicated a significant association between atopic dermatitis and all-cause dementia (adjusted hazard ratio: 1.15, 95% CI: 1.07–1.23). Subgroup analyses revealed an adjusted hazard ratio of 1.18 (95% CI: 1.08–1.27) for Alzheimer’s disease in patients with atopic dermatitis, and an adjusted hazard ratio of 1.37 (95% CI: 1.21–1.55) for all-cause dementia in patients with moderate-to-severe atopic dermatitis. However, MR analysis showed no significant causal link between atopic dermatitis and dementia, Alzheimer’s disease, vascular dementia, or cognitive performance. While the meta-analysis revealed a significant association, MR analysis did not substantiate a significant causal link. Future research should consider demographic variables and medication influences in unravelling the intricate atopic dermatitis–dementia interplay.

Downloads

Download data is not yet available.

References

Duong S, Patel T, Chang F. Dementia: What pharmacists need to know. Can Pharm J 2017; 150: 118-129

https://doi.org/10.1177/1715163517690745 DOI: https://doi.org/10.1177/1715163517690745

Wu Y-T, Clare L, Hindle JV, Nelis SM, Martyr A, Matthews FE. Dementia subtype and living well: results from the Improving the experience of Dementia and Enhancing Active Life (IDEAL) study. BMC Med 2018; 16: 1-9

https://doi.org/10.1186/s12916-018-1135-2 DOI: https://doi.org/10.1186/s12916-018-1135-2

World Health Organization. Geneva, Switzerland: World Health Organization. Fact sheets of dementia [Internet]. 2023 [cited 2024 Jun 19]. Available from: https:// www.who.int/news-room/fact-sheets/detail/dementia.

Wimo A, Seeher K, Cataldi R, Cyhlarova E, Dielemann JL, Frisell O, et al. The worldwide costs of dementia in 2019. Alzheimers Dement 2023; 10.1002/alz.12901

https://doi.org/10.1002/alz.12901 DOI: https://doi.org/10.1002/alz.12901

Cipriani G, Danti S, Picchi L, Nuti A, Fiorino MD. Daily functioning and dementia. Dement Neuropsycho 2020; 14: 93-102

https://doi.org/10.1590/1980-57642020dn14-020001 DOI: https://doi.org/10.1590/1980-57642020dn14-020001

Prizer LP, Zimmerman S. Progressive support for activities of daily living for persons living with dementia. Gerontol 2018; 58: S74-S87

https://doi.org/10.1093/geront/gnx103 DOI: https://doi.org/10.1093/geront/gnx103

Brown RT, Diaz-Ramirez LG, Boscardin WJ, Lee SJ, Williams BA, Steinman MA. Association of functional impairment in middle age with hospitalization, nursing home admission, and death. JAMA Intern Med 2019; 179: 668-675

https://doi.org/10.1001/jamainternmed.2019.0008 DOI: https://doi.org/10.1001/jamainternmed.2019.0008

Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet 2020; 396: 413-446

https://doi.org/10.1016/S0140-6736(20)30367-6 DOI: https://doi.org/10.1016/S0140-6736(20)30367-6

Tsakok T, Woolf R, Smith C, Weidinger S, Flohr C. Atopic dermatitis: the skin barrier and beyond. Br J Dermatol 2019; 180: 464-474

https://doi.org/10.1111/bjd.16934 DOI: https://doi.org/10.1111/bjd.16934

Pan TL, Bai YM, Cheng CM, Tsai SJ, Tsai CF, Su TP, et al. Atopic dermatitis and dementia risk: A nationwide longitudinal study. Ann Allergy Asthma Immunol 2021; 127: 200-205

https://doi.org/10.1016/j.anai.2021.03.001 DOI: https://doi.org/10.1016/j.anai.2021.03.001

Magyari A, Ye M, Margolis DJ, McCulloch CE, Cummings SR, Yaffe K, et al. Adult atopic eczema and the risk of dementia: A population-based cohort study. J Am Acad Dermatol 2022; 87: 314-322

https://doi.org/10.1016/j.jaad.2022.03.049 DOI: https://doi.org/10.1016/j.jaad.2022.03.049

Joh HK, Kwon H, Son KY, Yun JM, Cho SH, Han K, et al. Allergic Diseases and Risk of Incident Dementia and Alzheimer's Disease. Ann Neurol 2023; 93: 384-397

https://doi.org/10.1002/ana.26506 DOI: https://doi.org/10.1002/ana.26506

Yoon S, Kim K, Shin K, Kim HS, Kim B, Kim MB, et al. The safety of systemic Janus kinase inhibitors in atopic dermatitis: A systematic review and meta‐analysis of randomized controlled trials. J Eur Acad Dermatol Venereol 2024; 38: 52-61

https://doi.org/10.1111/jdv.19426 DOI: https://doi.org/10.1111/jdv.19426

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. [The PRISMA 2020 statement: an updated guideline for reporting systematic reviewsDeclaracion PRISMA 2020: una guia actualizada para la publicacion de revisiones sistematicas]. Rev Panam Salud Publica 2022; 46: e112

https://doi.org/10.26633/RPSP.2022.112 DOI: https://doi.org/10.26633/RPSP.2022.112

Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Oxford, 2000.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560

https://doi.org/10.1136/bmj.327.7414.557 DOI: https://doi.org/10.1136/bmj.327.7414.557

Ahn D, Kim J, Kang J, Kim YH, Kim K. Congenital anomalies and maternal age: A systematic review and meta‐analysis of observational studies. Acta Obstetric Gynecolog Scand 2022; 101: 484-498

https://doi.org/10.1111/aogs.14339 DOI: https://doi.org/10.1111/aogs.14339

Kim CM, Lee S, Hwang W, Son E, Kim TW, Kim K, et al. Obesity and periodontitis: A systematic review and updated meta-analysis. Front Endocrinol (Lausanne) 2022; 13: 999455

https://doi.org/10.3389/fendo.2022.999455 DOI: https://doi.org/10.3389/fendo.2022.999455

Budu-Aggrey A, Kilanowski A, Sobczyk MK, Shringarpure SS, Mitchell R, Reis K, et al. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation. Nat Commun 2023; 14: 6172

https://doi.org/10.1038/s41467-023-41180-2 DOI: https://doi.org/10.1038/s41467-023-41180-2

Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife 2018; 7: e34408

https://doi.org/10.7554/eLife.34408 DOI: https://doi.org/10.7554/eLife.34408

Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet 2018; 50: 693-698

https://doi.org/10.1038/s41588-018-0099-7 DOI: https://doi.org/10.1038/s41588-018-0099-7

Eriksson UK, Gatz M, Dickman PW, Fratiglioni L, Pedersen NL. Asthma, eczema, rhinitis and the risk for dementia. Dement Geriatr Cogn Disord 2008; 25: 148-156

https://doi.org/10.1159/000112729 DOI: https://doi.org/10.1159/000112729

Vingeliene S, Hiyoshi A, Carlberg M, Garcia‐Argibay M, Lentjes M, Fall K, et al. Atopic dermatitis, systemic inflammation and subsequent dementia risk. JEADV Clin Pract 2023; 10.1002/jvc2.249

https://doi.org/10.1002/jvc2.249 DOI: https://doi.org/10.1002/jvc2.249

Ramirez-Santana M. Limitations and biases in cohort studies. IntechOpen London, UK, 2018. DOI: https://doi.org/10.5772/intechopen.74324

Lee YH. Overview of Mendelian randomization analysis. Journal of Rheumatic Diseases 2020; 27: 241-246. DOI: https://doi.org/10.4078/jrd.2020.27.4.241

Sanderson E, Glymour MM, Holmes MV, Kang H, Morrison J, Munafò MR, et al. Mendelian randomization. Nature Reviews Methods Primers 2022; 2: 6. DOI: https://doi.org/10.1038/s43586-021-00092-5

Ferretti MT, Cuello AC. Does a pro-inflammatory process precede Alzheimer's disease and mild cognitive impairment? Curr Alzheimer Res 2011; 8: 164-174

https://doi.org/10.2174/156720511795255982 DOI: https://doi.org/10.2174/156720511795255982

Griffin WS. Neuroinflammatory cytokine signaling and Alzheimer's disease. N Engl J Med 2013; 368: 770-771

https://doi.org/10.1056/NEJMcibr1214546 DOI: https://doi.org/10.1056/NEJMcibr1214546

Meraz-Rios MA, Toral-Rios D, Franco-Bocanegra D, Villeda-Hernandez J, Campos-Pena V. Inflammatory process in Alzheimer's Disease. Front Integr Neurosci 2013; 7: 59

https://doi.org/10.3389/fnint.2013.00059 DOI: https://doi.org/10.3389/fnint.2013.00059

Xiong Z, Thangavel R, Kempuraj D, Yang E, Zaheer S, Zaheer A. Alzheimer's disease: evidence for the expression of interleukin-33 and its receptor ST2 in the brain. J Alzheimers Dis 2014; 40: 297-308

https://doi.org/10.3233/JAD-132081 DOI: https://doi.org/10.3233/JAD-132081

Abd Rachman Isnadi MF, Chin VK, Abd Majid R, Lee TY, Atmadini Abdullah M, Bello Omenesa R, et al. Critical Roles of IL-33/ST2 Pathway in Neurological Disorders. Mediators Inflamm 2018; 2018: 5346413

https://doi.org/10.1155/2018/5346413 DOI: https://doi.org/10.1155/2018/5346413

Pfab F, Valet M, Napadow V, Tölle TR, Behrendt H, Ring J, et al. Itch and the brain. Chem Immunol Allergy 2012; 98: 253-265 DOI: https://doi.org/10.1159/000336529

https://doi.org/10.1159/00033652913

Schut C, Mochizuki H, Grossman SK, Lin AC, Conklin CJ, Mohamed FB, et al. Brain Processing of Contagious Itch in Patients with Atopic Dermatitis. Front Psychol 2017; 8: 1267

https://doi.org/10.3389/fpsyg.2017.01267 DOI: https://doi.org/10.3389/fpsyg.2017.01267

Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer's disease. Nat Immunol 2015; 16: 229-236

https://doi.org/10.1038/ni.3102 DOI: https://doi.org/10.1038/ni.3102

Shi Y, Holtzman DM. Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat Rev Immunol 2018; 18: 759-772

https://doi.org/10.1038/s41577-018-0051-1 DOI: https://doi.org/10.1038/s41577-018-0051-1

Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 2015; 16: 358-372

https://doi.org/10.1038/nrn3880 DOI: https://doi.org/10.1038/nrn3880

Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015; 14: 388-405

https://doi.org/10.1016/S1474-4422(15)70016-5 DOI: https://doi.org/10.1016/S1474-4422(15)70016-5

Griffin WST, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A 1989; 86: 7611-7615

https://doi.org/10.1073/pnas.86.19.7611 DOI: https://doi.org/10.1073/pnas.86.19.7611

Griffin WST, Barger SW. Neuroinflammatory cytokines - The common thread in Alzheimer pathogenesis. Eur Neurol Rev 2011; 6: 89-96

https://doi.org/10.17925/enr.2011.06.02.89 DOI: https://doi.org/10.17925/ENR.2011.06.02.89

Jones MK, Nair A, Gupta M. Mast cells in neurodegenerative disease. Front Cell Neurosci 2019; 13; 171

https://doi.org/10.3389/fncel.2019.00171 DOI: https://doi.org/10.3389/fncel.2019.00171

Hendriksen E, van Bergeijk D, Oosting RS, Redegeld FA. Mast cells in neuroinflammation and brain disorders. Neurosci Biobehav Rev 2017; 79: 119-133

https://doi.org/10.1016/j.neubiorev.2017.05.001 DOI: https://doi.org/10.1016/j.neubiorev.2017.05.001

Piette F, Belmin J, Vincent H, Schmidt N, Pariel S, Verny M, et al. Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: A randomised, placebo-controlled phase 2 trial. Alzheimers Res Ther 2011; 3: 16

https://doi.org/10.1186/alzrt75 DOI: https://doi.org/10.1186/alzrt75

Wang L, Gao S, Yu M, Sheng Z, Tan W. Association of asthma with coronary heart disease: A meta analysis of 11 trials. PLoS ONE 2017; 12: e0179335

https://doi.org/10.1371/journal.pone.0179335 DOI: https://doi.org/10.1371/journal.pone.0179335

Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 2018; 14: 133-150

https://doi.org/10.1038/nrneurol.2017.188 DOI: https://doi.org/10.1038/nrneurol.2017.188

Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer's disease. Lancet 2021; 397: 1577-1590

https://doi.org/10.1016/S0140-6736(20)32205-4 DOI: https://doi.org/10.1016/S0140-6736(20)32205-4

Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern Med 2015; 175: 401-407

https://doi.org/10.1001/jamainternmed.2014.7663 DOI: https://doi.org/10.1001/jamainternmed.2014.7663

Wacholder S, Hartge P, Lubin JH, Dosemeci M. Non-differential misclassification and bias towards the null: a clarification. Occup Environ Med 1995; 52: 557-558

https://doi.org/10.1136/oem.52.8.557 DOI: https://doi.org/10.1136/oem.52.8.557

Metelli S, Chaimani A. Challenges in meta-analyses with observational studies. BMJ Ment Health 2020; 23: 83-87.

https://doi.org/10.1136/ebmental-2019-300129 DOI: https://doi.org/10.1136/ebmental-2019-300129

Clayton GL, Gonçalves A, Goulding N, Borges MC, Holmes MV, Davey G, et al. A framework for assessing selection and misclassification bias in mendelian randomisation studies: an illustrative example between body mass index and covid-19. BMJ 2023; 381: e072148.

https://doi.org/10.1136/bmj-2022-072148 DOI: https://doi.org/10.1136/bmj-2022-072148

Downloads

Additional Files

Published

2025-01-03

How to Cite

Gwak, Y.-S., Kim, S.-Y., Woo, C.-E., Shin, K., Son, E., Kim, J.-W., … Kim, Y. H. (2025). Association between Atopic Dermatitis and Dementia: Evidence from Systematic Review, Meta-analysis, and Mendelian Randomization. Acta Dermato-Venereologica, 105, adv41321. https://doi.org/10.2340/actadv.v105.41321

Issue

Vol. 105 (2025)

Section

Review

Categories

License

Copyright (c) 2025 Yeon-Su Gwak, Seo-Yeon Kim, Chae-Eon Woo, Kihyuk Shin, Eunjeong Son, Jin-Woo Kim, Sung-Jin Kim, Tae-Jin Song, Hae Ryoun Park, Kihun Kim, Dai Sik Ko, Yun Hak Kim

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.

Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.

Crossref
Scopus
Google Scholar
Europe PMC