{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:05:15Z","timestamp":1779300315029,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Geriatrics"],"abstract":"<jats:p>Background\/Objectives: To evaluate the association between fibromyalgia and dementia, with emphasis on temporal directionality and Alzheimer\u2019s disease-related dementia. Methods: We conducted a nationwide, population-based matched case\u2013control study including 9232 patients with fibromyalgia and 46,160 age- and sex-matched controls. Diagnoses in the Leumit Health Services database are recorded using a hybrid coding scheme that combines ICD-9-CM and WHO ICD-10 codes; the specific codes used to ascertain fibromyalgia and each dementia subtype are listed in the Methods. Outcomes were assessed within two predefined windows: up to 20 years before and up to 10 years after fibromyalgia diagnosis. Alzheimer disease-related dementia was defined as the primary outcome. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: During the 20 years preceding fibromyalgia diagnosis, no increased dementia prevalence was observed; Alzheimer disease-related dementia was less frequent among fibromyalgia patients (0.16% vs. 0.31%; absolute difference \u22120.15 percentage points; OR 0.52, 95% CI 0.31\u20130.89). In contrast, during the 10 years following diagnosis, fibromyalgia was associated with a higher prevalence of Alzheimer\u2019s disease-related dementia (1.43% vs. 0.99%; absolute difference +0.44 percentage points; OR 1.45, 95% CI 1.18\u20131.78). No consistent associations were found for other dementia subtypes, which should be interpreted as exploratory given low event counts. Conclusions: Fibromyalgia is associated with a higher prevalence of Alzheimer\u2019s disease-related dementia in the years following diagnosis, with no evidence of pre-diagnostic elevation. Although this temporal pattern argues against reverse causation, the prevalence-based design and residual confounding preclude causal inference. Fibromyalgia should be regarded as a potential risk marker for subsequent Alzheimer-related neurodegeneration rather than a demonstrated causal factor.<\/jats:p>","DOI":"10.3390\/geriatrics11030061","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:34Z","timestamp":1779295174000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibromyalgia and Risk of Alzheimer\u2019s DiseaseRelated Dementia: A Nationwide Bidirectional Case\u2013Control Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7713-423X","authenticated-orcid":false,"given":"Eli","family":"Magen","sequence":"first","affiliation":[{"name":"Leumit Health Services, Tel Aviv-Yafo 6473817, Israel"},{"name":"Department of Medicine A, Assuta Ashdod University Medical Center, Ben-Gurion University of the Negev, Ashdod 7747629, Israel"},{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5236-8538","authenticated-orcid":false,"given":"Israel","family":"Magen","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel"},{"name":"Urology Department, Assuta Ashdod University Medical Center, Ben-Gurion University of the Negev, Ashdod 7747629, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-0236","authenticated-orcid":false,"given":"Eugene","family":"Merzon","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv-Yafo 6473817, Israel"},{"name":"Adelson School of Medicine, Ariel University, Ariel 4070000, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-7152","authenticated-orcid":false,"given":"Ilan","family":"Green","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv-Yafo 6473817, Israel"},{"name":"Department of Family Medicine, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv-Yafo 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2406-6402","authenticated-orcid":false,"given":"Avivit","family":"Golan-Cohen","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv-Yafo 6473817, Israel"},{"name":"Department of Family Medicine, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv-Yafo 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Vinker","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv-Yafo 6473817, Israel"},{"name":"Department of Family Medicine, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv-Yafo 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-8896","authenticated-orcid":false,"given":"Ariel","family":"Israel","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv-Yafo 6473817, Israel"},{"name":"Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv-Yafo 6139001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e25032","DOI":"10.5152\/eurjrheum.2025.0032","article-title":"Fibromyalgia: Update on Pathogenesis and Management","volume":"12","author":"Wu","year":"2025","journal-title":"Eur. J. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Abenavoli, E., Berti, V., Nerattini, M., Sarzi-Puttini, P., Filippou, G., Lucia, A., Pari, G., Pallanti, S., Salaffi, F., and Carotti, M. (2025). Fibromyalgia in the Era of Brain PET\/CT Imaging. J. Clin. Med., 14.","DOI":"10.3390\/jcm14124166"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.semarthrit.2014.01.001","article-title":"Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI","volume":"44","author":"Cagnie","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2025). A Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010165"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/acr.24089","article-title":"Fibrofog in Daily Life: An Examination of Ambulatory Subjective and Objective Cognitive Function in Fibromyalgia","volume":"72","author":"Kratz","year":"2020","journal-title":"Arthritis Care Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1534","DOI":"10.1016\/S2214-109X(24)00264-X","article-title":"The global macroeconomic burden of Alzheimer\u2019s disease and other dementias: Estimates and projections for 152 countries or territories","volume":"12","author":"Chen","year":"2024","journal-title":"Lancet Glob. Health"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhu, X., Yu, J., Lai, X., Wang, X., Deng, J., Long, Y., and Li, B. (2025). Global Burden of Alzheimer\u2019s disease and other dementias in adults aged 65 years and older, 1991\u20132021: Population-based study. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1585711"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e70235","DOI":"10.1002\/alz.70235","article-title":"2025 Alzheimer\u2019s disease facts and figures","volume":"21","author":"Gaugler","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.2147\/JPR.S491626","article-title":"Effects of Mental Disorders on Fibromyalgia Mediated by Insomnia: A Mendelian Randomization Study","volume":"17","author":"Chang","year":"2024","journal-title":"J. Pain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.jad.2024.03.077","article-title":"Shared comorbidity of depression, migraine, insomnia, and fibromyalgia in a population-based sample","volume":"354","author":"Lee","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41398-026-03924-8","article-title":"Chronic pain and risk of cognitive impairment: A meta-analysis of longitudinal cohort studies","volume":"16","author":"Qiu","year":"2026","journal-title":"Transl. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10433-024-00812-2","article-title":"Association between chronic pain and dementia: A systematic review and meta-analysis","volume":"21","author":"Wang","year":"2024","journal-title":"Eur. J. Ageing"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.amjms.2017.09.002","article-title":"Fibromyalgia and Risk of Dementia\u2014A Nationwide, Population-Based, Cohort Study","volume":"355","author":"Tzeng","year":"2018","journal-title":"Am. J. Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/1756-185X.12734","article-title":"Fibromyalgia syndrome and cognitive dysfunction in elderly: A case series","volume":"19","author":"Nishioka","year":"2016","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17446","DOI":"10.1038\/s41598-025-01070-7","article-title":"Brain structural differences between fibromyalgia patients and healthy control subjects: A source-based morphometric study","volume":"15","author":"Agoalikum","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1097\/EDE.0b013e3181a819a1","article-title":"Overadjustment bias and unnecessary adjustment in epidemiologic studies","volume":"20","author":"Schisterman","year":"2009","journal-title":"Epidemiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/acr.22403","article-title":"Are fibromyalgia patients cognitively impaired? Objective and subjective neuropsychological evidence","volume":"67","author":"Tesio","year":"2015","journal-title":"Arthritis Care Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/RHU.0000000000000213","article-title":"Cross-sectional neurocognitive data do not support a transition from fibrofog to Alzheimer disease in fibromyalgia patients","volume":"21","author":"Leavitt","year":"2015","journal-title":"J. Clin. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4103\/IJPSYM.IJPSYM_45_20","article-title":"Reverse Causation, Physical Inactivity, and Dementia","volume":"42","author":"Andrade","year":"2020","journal-title":"Indian J. Psychol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e256637","DOI":"10.1001\/jamanetworkopen.2025.6637","article-title":"Detection Bias in EHR-Based Research on Clinical Exposures and Dementia","volume":"8","author":"Wang","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2147\/JPR.S74900","article-title":"Electronic medical record data to identify variables associated with a fibromyalgia diagnosis: Importance of health care resource utilization","volume":"8","author":"Masters","year":"2015","journal-title":"J. Pain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12979-025-00529-5","article-title":"Systemic inflammation as a central player in the initiation and development of Alzheimer\u2019s disease","volume":"22","author":"Bayraktaroglu","year":"2025","journal-title":"Immun. Ageing"},{"key":"ref_23","first-page":"957","article-title":"Fibromyalgia: One year in review 2025","volume":"43","author":"Iannuccelli","year":"2025","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Safiri, S., Ghaffari Jolfayi, A., Fazlollahi, A., Morsali, S., Sarkesh, A., Daei Sorkhabi, A., Golabi, B., Aletaha, R., Motlagh Asghari, K., and Hamidi, S. (2024). Alzheimer\u2019s disease: A comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1474043"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3949\/ccjm.90a.22019","article-title":"Central sensitization, chronic pain, and other symptoms: Better understanding, better management","volume":"90","author":"Volcheck","year":"2023","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Brezic, N., Gligorevic, S., Sic, A., and Knezevic, N.N. (2025). Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47040259"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/anae.70021","article-title":"A systematic review of brain health in adults with chronic pain","volume":"81","author":"Lee","year":"2026","journal-title":"Anaesthesia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2147\/JPR.S71959","article-title":"Fibromyalgia patients have reduced hippocampal volume compared with healthy controls","volume":"8","author":"McCrae","year":"2015","journal-title":"J. Pain Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Long, Y., Xie, X., Wang, Y., Xu, J., Gao, Z., Fang, X., Xu, T., Zhang, N., Lv, D., and Wu, T. (2024). Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1380121"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"120340","DOI":"10.1016\/j.jad.2025.120340","article-title":"The global prevalence of depression and anxiety among fibromyalgia patients: A systematic review and meta-analysis","volume":"393","author":"Jafari","year":"2026","journal-title":"J. Affect. Disord."},{"key":"ref_31","first-page":"1136","article-title":"Unravelling the relationship between anxiety, autonomic nervous system dysfunction and fibromyalgia: A systematic review","volume":"43","author":"Demo","year":"2025","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cohen, J., Mathew, A., Dourvetakis, K.D., Sanchez-Guerrero, E., Pangeni, R.P., Gurusamy, N., Aenlle, K.K., Ravindran, G., Twahir, A., and Isler, D. (2024). Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders. Cells, 13.","DOI":"10.3390\/cells13060511"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12974-024-03018-6","article-title":"Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice","volume":"21","author":"Wakatsuki","year":"2024","journal-title":"J. Neuroinflamm."}],"container-title":["Geriatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3417\/11\/3\/61\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:05:54Z","timestamp":1779296754000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3417\/11\/3\/61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["geriatrics11030061"],"URL":"https:\/\/doi.org\/10.3390\/geriatrics11030061","relation":{},"ISSN":["2308-3417"],"issn-type":[{"value":"2308-3417","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]}}}