{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:47:28Z","timestamp":1788554848407,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T00:00:00Z","timestamp":1728172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Alzheimer\u2019s disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer\u2019s disease treatment combinations, the number of concomitant medications, and the occurrence of AEs. Materials and Methods: Data from the Japanese Adverse Drug Event Report database, spanning from April 2004 to June 2020, were analyzed. Patients aged 60 and older with Alzheimer\u2019s disease treated with AChEIs (donepezil, galantamine, and rivastigmine) or the NMDA receptor antagonist memantine were included. Logistic regression models were employed to assess the association between AEs and Alzheimer\u2019s disease drug combinations, as well as the number of concomitant medications. Results: Among 2653 patients, 47.7% were prescribed five or more drugs. The frequency of AEs was 6.4% for bradycardia, 4.6% for pneumonia, 3.6% for altered state of consciousness, 3.5% for seizures, 3.5% for decreased appetite, 3.5% for vomiting, 3.4% for loss of consciousness, 3.4% for fracture, 3.2% for cardiac failure, and 3.0% for falls. The combination of memantine with AChEIs was associated with a higher risk of bradycardia, whereas donepezil alone was linked to a reduced risk of fractures and falls. Polypharmacy was significantly correlated with an increased incidence of AEs, particularly altered state of consciousness, decreased appetite, vomiting, and falls. The adjusted odds ratios for using five or more drugs compared to no drugs was 10.45 for altered state of consciousness, 7.92 for decreased appetite, 4.74 for vomiting, and 5.95 for falls. Conclusions: In the treatment of Alzheimer\u2019s disease, the occurrence of AEs is associated with the number of concurrent medications, independently of the known AEs of Alzheimer\u2019s disease drugs and their combination patterns.<\/jats:p>","DOI":"10.3390\/medicina60101633","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:23:18Z","timestamp":1728282198000},"page":"1633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association between Polypharmacy and Adverse Events in Patients with Alzheimer\u2019s Disease: An Analysis of the Japanese Adverse Drug Event Report Database (JADER)"],"prefix":"10.3390","volume":"60","author":[{"given":"Nobuhiro","family":"Otani","sequence":"first","affiliation":[{"name":"Department of Public Health, Faculty of Medicine, Kagawa University, Miki 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6712-3951","authenticated-orcid":false,"given":"Kanae","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Medicine, Kagawa University, Miki 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8847-3667","authenticated-orcid":false,"given":"Nlandu Roger","family":"Ngatu","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Medicine, Kagawa University, Miki 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitsu","family":"Murakami","sequence":"additional","affiliation":[{"name":"Cancer Center, Kagawa University, Miki 761-0793, Kagawa, Japan"},{"name":"Department of Anesthesiology, Faculty of Medicine, Kagawa University, Miki 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yamadori","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, Kagawa University, Miki 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9824-565X","authenticated-orcid":false,"given":"Tomohiro","family":"Hirao","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Medicine, Kagawa University, Miki 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,6]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, August 04). 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