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Donepezil acts primarily on the cholinergic system as a symptomatic treatment, but it also has potential for disease modification and may reduce the rate of progression of AD. This review explores the potential for disease modifying effects of donepezil. Several neuroprotective mechanisms that are independent of cholinesterase inhibition, are suggested. Donepezil has demonstrated a range of effects, including protecting against amyloid \u03b2, ischaemia and glutamate toxicity; slowing of progression of hippocampal atrophy; and up\u2010regulation of nicotinic acetylcholine receptors. Clinically, early and continuous treatment with donepezil is considered to preserve cognitive function more effectively than delayed treatment. The possible neuroprotective effects of donepezil and the potential for disease pathway modification highlight the importance of early diagnosis and treatment initiation in AD.<\/jats:p>","DOI":"10.1111\/bph.14030","type":"journal-article","created":{"date-parts":[[2017,9,13]],"date-time":"2017-09-13T11:06:36Z","timestamp":1505300796000},"page":"4224-4232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Beyond symptomatic effects: potential of donepezil as a neuroprotective agent and disease modifier in Alzheimer's disease"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-9598","authenticated-orcid":false,"given":"Seung Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Neurology Hanyang University College of Medicine  Seoul Korea"},{"name":"Seongdong\u2010Gu Regional Center for Dementia  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagaendran","family":"Kandiah","sequence":"additional","affiliation":[{"name":"Department of Neurology National Neuroscience Institute and Duke\u2010NUS Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung\u2010Lung","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Neurology Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang\u2010Gung University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuthamanee","family":"Suthisisang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Mahidol University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chesda","family":"Udommongkol","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine Phramongkutklao Hospital  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-4021","authenticated-orcid":false,"given":"Amitabh","family":"Dash","sequence":"additional","affiliation":[{"name":"Eisai Singapore Pte. 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