{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:25:49Z","timestamp":1792301149661,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acetylcholine signaling is attenuated in early Alzheimer\u2019s disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The modulation of the functional deficit of the cholinergic system as a pharmacological target could therefore have a clinical benefit, which is not to be neglected. This systematic review was conducted to identify clinical trials, which evaluated the safety and efficacy of nicotinic acetylcholine receptor agonists using Clinicaltrial (CT) and EudraCT databases. Structured searches identified 39 trials, which used 15 different drugs designed to increase the function of the nAChRs. Most of the identified clinical trials were phase II trials, with some of them classified as ongoing for several years. The systematic screening of the literature led to the selection of 14 studies out of the 8261 bibliographic records retrieved. Six trials reported detailed data on adverse events associated with the intervention, while twelve trials reported data on efficacy measures, such as attention, behavior and cognition. Overall, smost of the physical side effects of cholinergic agonists were reported to be well tolerated. Some trials also reported improvements in attention. However, the efficacy of these drugs in other cognitive and behavioral outcomes remains highly controversial.<\/jats:p>","DOI":"10.3390\/cells13030237","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T08:56:01Z","timestamp":1706259361000},"page":"237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Systematic Review on Drugs Acting as Nicotinic Acetylcholine Receptor Agonists in the Treatment of Dementia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-7799","authenticated-orcid":false,"given":"Alessio","family":"Crestini","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3687-969X","authenticated-orcid":false,"given":"Roberto","family":"Rivabene","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3949-3127","authenticated-orcid":false,"given":"Antonio","family":"Ancidoni","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8468-0677","authenticated-orcid":false,"given":"Paolo","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, 04100 Latina, Italy"},{"name":"ICOT (Institute of Traumatology and Orthopaedic Surgery), 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4868-5435","authenticated-orcid":false,"given":"Ada Maria","family":"Tata","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies Charles Darwin, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Research Center in Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Fabrizi","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy"},{"name":"Doctoral School, The Catholic University of Valencia San Vicente M\u00e1rtir, 46001 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Locuratolo","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-3758","authenticated-orcid":false,"given":"Nicola","family":"Vanacore","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Lacorte","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-4969","authenticated-orcid":false,"given":"Paola","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"Alzheimer disease in the United States (2010\u20132050) estimated using the 2010 census","volume":"80","author":"Hebert","year":"2013","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18008","DOI":"10.1523\/JNEUROSCI.1402-13.2013","article-title":"Changes in Brain Function Occur Years before the Onset of Cognitive Impairment","volume":"33","author":"Goh","year":"2013","journal-title":"J. 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