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Library"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe infections have been linked to an increased risk of dementia, but both conditions often coexist with other illnesses that may confound this association. Using nationwide Finnish health registry data, we examined the role of noninfectious mental and physical illnesses in the association between severe infections and dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      This register-based study included 62,555 individuals aged 65 or older in Finland in 2016 who were diagnosed with late-onset dementia between 2017 and 2020 and 312,772 dementia-free controls matched for year of birth, sex, and the follow-up period. Analyses were adjusted for education, marital status, employment, and area of residence, with age and sex accounted for through the matched conditional design and analysis. Applying a 1-year lag period, we identified 29 hospital-treated diseases that occurred 1\u201321 years before dementia diagnosis in cases (or index date in controls), had a prevalence of \u2265 1% prior to dementia, and were robustly associated with increased dementia risk (confounder-adjusted rate ratio\u2009\u2265\u20091.20,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.000294). In addition to 2 infectious diseases (cystitis and bacterial infection of an unspecified site), these included 27 mental, behavioural, digestive, endocrine, cardiometabolic, neurological, and eye diseases, as well as injuries. 29,376 (47%) of the dementia cases had at least one of these diseases diagnosed before dementia. The associations between the two infectious diseases and dementia risk were not attributable to the 27 comorbid dementia-related diseases diagnosed before infections. The adjusted rate ratio for cystitis was 1.22 (95% confidence interval (CI) [1.17, 1.27];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) before and 1.19 (95% CI [1.14, 1.24];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) after adjustment for comorbidities, while for bacterial infections of an unspecified site, the rate ratios were 1.21 (95% CI [1.16, 1.28];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and 1.19 (95% CI [1.13, 1.25];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), respectively. The findings were comparable across subgroups defined by sex and education, and stronger for cases of early onset dementia. We were not able to directly assess psychosocial, behavioural, or biological confounders that are not captured in nationwide registries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This nationwide Finnish study identified several mental and physical diseases that are associated with an increased risk of dementia and showed that the increased incidence of dementia among individuals with severe infections is not attributable to these comorbid conditions. These results support the role of severe infections as independent risk factors for dementia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004688","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:22:01Z","timestamp":1774372921000},"page":"e1004688","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["The role of noninfectious comorbidities in the association between severe infections and risk of dementia in Finland: A nationwide registry study"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4886-8151","authenticated-orcid":true,"given":"Pyry N.","family":"Sipil\u00e4","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8499-2008","authenticated-orcid":true,"given":"Kaarina","family":"Korhonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-2692","authenticated-orcid":true,"given":"Joni V.","family":"Lindbohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4699-5627","authenticated-orcid":true,"given":"Mika","family":"Kivim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pekka","family":"Martikainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"issue":"11","key":"pmed.1004688.ref001","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/S1473-3099(21)00144-4","article-title":"Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort","volume":"21","author":"PN Sipil\u00e4","year":"2021","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"pmed.1004688.ref002","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.3233\/JAD-200303","article-title":"Common bacterial infections and risk of dementia or cognitive decline: a systematic review","volume":"76","author":"R Muzambi","year":"2020","journal-title":"J Alzheimers Dis"},{"issue":"7","key":"pmed.1004688.ref003","doi-asserted-by":"crossref","DOI":"10.1016\/S2666-7568(21)00118-5","article-title":"Assessment of common infections and incident dementia using UK primary and secondary care data: a historical cohort study","volume":"2","author":"R Muzambi","year":"2021","journal-title":"Lancet Healthy Longev"},{"issue":"9","key":"pmed.1004688.ref004","article-title":"Hospital-treated infections in early- and mid-life and risk of Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis: a nationwide nested case-control study in Sweden","volume":"19","author":"J Sun","year":"2022","journal-title":"PLoS Med"},{"issue":"6","key":"pmed.1004688.ref005","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/s43587-024-00621-3","article-title":"Associations of hospital-treated infections with subsequent dementia: nationwide 30-year analysis","volume":"4","author":"LS Richmond-Rakerd","year":"2024","journal-title":"Nat Aging"},{"key":"pmed.1004688.ref006","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.dadm.2016.08.004","article-title":"Systemic and localized extra-central nervous system bacterial infections and the risk of dementia among US veterans: a retrospective cohort study","volume":"4","author":"F Mawanda","year":"2016","journal-title":"Alzheimers Dement (Amst)"},{"issue":"11","key":"pmed.1004688.ref007","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41582-021-00549-x","article-title":"Peripheral and central immune system crosstalk in Alzheimer disease - 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