{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:16:31Z","timestamp":1791656191998,"version":"4.3.4"},"reference-count":113,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The term \u2018dementia\u2019 encompasses a diverse group of progressive neurodegenerative disorders, the common feature of which is the deterioration of higher cortical functions. This process not only involves memory deficits and language communication disorders, but also executive dysfunction and loss of emotional control, which ultimately leads to a complete loss of the patient\u2019s independence. Within this group of disorders, Alzheimer\u2019s disease (AD) presents the most serious clinical challenge, characterized by a unique neuropathological triad: the presence of extracellular \u03b2-amyloid plaques, intracellular neurofibrillary tangles of tau protein, and widespread dysfunction of cholinergic transmission. The cholinergic hypothesis remains the cornerstone of the current understanding of cognitive impairment in AD. It posits that progressive dementia is caused by the selective degeneration of neurons in the anterior basal forebrain, resulting in a drastic reduction in acetylcholine (ACh) levels in the synaptic cleft. In the absence of a causal treatment, acetylcholinesterase inhibitors (AChEIs) remain the standard of care. Their pharmacological action is based on the inhibition of the AChE enzyme, which allows neurotransmission deficits to be compensated for by prolonging the half-life of acetylcholine at the synapse. This literature review presents a synthesis of the efficacy and safety of classic and novel AChEIs. A comprehensive search of the PubMed, Scopus, and Cochrane Library databases was conducted for clinical data published up to 2026. Evidence from key trials indicates that standard AChEIs induce significant cognitive stabilization compared to placebo, with rivastigmine maximizing daily living parameters via transdermal delivery. However, their therapeutic impact remains strictly symptomatic without arresting neurodegeneration. Conversely, emerging agents like huperzine A and the translation-blocker Posiphen demonstrate disease-modifying potential by modulating CSF biomarkers associated with amyloid and tau proteins. Clinically, while traditional regimens are limited by gastrointestinal toxicities, transitioning toward innovative multi-target structures represents a necessary shift to address both cognitive decline and neurodegeneration.<\/jats:p>","DOI":"10.3390\/ijms27135733","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:49:23Z","timestamp":1782434963000},"page":"5733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of the Efficacy of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer\u2019s Disease, Literature Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Wiktor","family":"Petrov","sequence":"first","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9150-3768","authenticated-orcid":false,"given":"Dawid","family":"\u015alebioda","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4798-2167","authenticated-orcid":false,"given":"Rozalia","family":"Kozi\u0144ska","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Kukla","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Petrov","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8898-7609","authenticated-orcid":false,"given":"Mateusz","family":"Sroka","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Tesyna","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Pu\u017aniak","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Kudli\u0144ski","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tymon","family":"Rejda","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2503-7473","authenticated-orcid":false,"given":"Izabela","family":"Skowron","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-8114","authenticated-orcid":false,"given":"Agnieszka","family":"Ch\u0142opa\u015b-Konowa\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Division of Molecular Techniques, Wroclaw Medical University, Sklodowskiej-Curie 52, 50-369 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2023). 2023 Alzheimer\u2019s disease facts figures. 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