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However, its influence on transitions between these health states remains understudied in large, population-based cohorts. Using data from 361,970 UK Biobank participants aged 50 and older with up to 15 years of follow-up, we examined the association between polypharmacy, defined as the use of five or more medications, and transitions between health states: healthy, dementia, PD, and mortality. Multistate parametric models, including Weibull regression, were employed to estimate these associations, adjusting for demographics, socioeconomic status, cardiovascular health, and comorbidities. Latent class analysis was used to identify specific medication combinations associated with health transitions. Polypharmacy was significantly associated with higher risks of transitioning from healthy to dementia (hazard ratio [HR], 1.15; 95% CI, 1.07\u20131.23) and from healthy to death (HR, 1.11; 95% CI, 1.08\u20131.09). Women exhibited better cardiovascular health but higher polypharmacy prevalence compared to men. Latent class analysis revealed that certain medication combinations, such as omega-3 fatty acids and multivitamins, were inversely associated with dementia and mortality, independent of polypharmacy status. These findings highlight the complex relationship between polypharmacy and health transitions in older adults. Careful medication management may mitigate risks associated with polypharmacy, particularly among individuals at risk for neurodegenerative diseases. Further research is warranted to investigate the potential protective effects of specific medication combinations on health outcomes.<\/jats:p>","DOI":"10.1007\/s11357-025-01586-w","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T14:55:52Z","timestamp":1741877752000},"page":"4349-4367","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polypharmacy and its association with dementia, Parkinson\u2019s disease, and mortality risk in UK adults: a multistate modeling approach"],"prefix":"10.1007","volume":"47","author":[{"given":"Jordan","family":"Weiss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-4523","authenticated-orcid":false,"given":"May A.","family":"Beydoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Georgescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Maldonado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind A.","family":"Beydoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-3838","authenticated-orcid":false,"given":"Nicole","family":"Noren Hooten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyo","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Nieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele K.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan B.","family":"Zonderman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"issue":"8","key":"1586_CR1","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1093\/gerona\/glv013","volume":"70","author":"CJ Charlesworth","year":"2015","unstructured":"Charlesworth CJ, Smit E, Lee DS, Alramadhan F, Odden MC. 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Written informed consent was not required for this investigation as it adhered to national laws and institutional regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}