{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:30:31Z","timestamp":1790879431897,"version":"4.1.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020033","name":"Alzheimer-forskningsfonden","doi-asserted-by":"publisher","award":["670-181003"],"award-info":[{"award-number":["670-181003"]}],"id":[{"id":"10.13039\/100020033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Clinical Medicine, University of Copenhagen"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer's Disease Reports"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous evidence suggests serum concentrations of donepezil varies in clinical populations and that a dose higher than standard may have additional positive effect on cognition. Therapeutic drug monitoring (TDM) is a tool for dose optimization (DO) whereby treatment is adjusted based on previous quantification of the prescribed drug.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Investigate whether TDM-based DO of donepezil or memantine improves clinical outcomes and\/or reduce the frequency of adverse reactions (ARs) in neurodegenerative conditions commonly treated with these two study drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-blinded 1:1 randomized controlled study in an outpatient memory clinic. Eligible participants either newly diagnosed with Alzheimer's disease dementia (AD), dementia with Lewy bodies (DLB), or Parkinson's disease dementia (PDD) scheduled for treatment with donepezil or memantine. The intervention group received TDM based DO. The control group received DO solely based on clinical assessment. Clinical outcomes were change in Mini-Mental State Examination, Addenbrooke's Cognitive Examination, Neuropsychiatric Inventory, and Disability Assessment in Dementia from baseline to 12 months. Additionally, data on incidence and severity of ARs and proportion of participants with a serum concentration within the therapeutic reference range were collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>132 participants recruited (125 AD, 7 DLB, none with PDD) of whom 107 completed the study (101 AD and 6 DLB), fewer in the control group than planned. Statistical analysis did not reveal significant differences between groups neither for clinical outcomes nor for frequency of ARs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TDM based DO did not significantly improve clinical outcomes nor reduce the frequency of ARs albeit important caveats to the results apply.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ClincialTrials.gov identifier<\/jats:title>\n                    <jats:p>NCT04117178 (first posted October 7, 2019).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/25424823241289373","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T02:44:21Z","timestamp":1732502661000},"page":"1516-1528","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic drug monitoring for dose optimization in Alzheimer's disease and in dementia with Lewy bodies: A randomized single-blinded clinical trial"],"prefix":"10.1177","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-2245","authenticated-orcid":false,"given":"Michael H\u00e9n Forbord","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Neurology, Zealand University Hospital, Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan Chrilles","family":"Zibrandtsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Herlev Hospital, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Johannsen","sequence":"additional","affiliation":[{"name":"Global Development, Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkert","family":"Siersma","sequence":"additional","affiliation":[{"name":"The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Borg","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"The Danish Epilepsy Centre, Dianalund, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Borggaard","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Holb\u00e6k Hospital, Holb\u00e6k, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"H\u00f8gh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zealand University Hospital, Roskilde, Denmark"},{"name":"Department of Neurology, Herlev Hospital, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,11,24]]},"reference":[{"key":"bibr1-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-116492"},{"key":"bibr2-25424823241289373","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200825020-00008"},{"key":"bibr3-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2010.06.019"},{"key":"bibr4-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2318-13-56"},{"key":"bibr5-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000152"},{"key":"bibr6-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1286287"},{"key":"bibr7-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e3181c71be9"},{"key":"bibr8-25424823241289373","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746070-00005"},{"key":"bibr9-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2010.03048.x"},{"key":"bibr10-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2005.10.005"},{"key":"bibr11-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"bibr12-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"bibr13-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21507"},{"key":"bibr14-25424823241289373","first-page":"745","volume":"170","author":"K\u00f8rner EA","year":"2008","journal-title":"Ugeskr Laeger"},{"key":"bibr15-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1159\/000209271"},{"key":"bibr16-25424823241289373","first-page":"905","volume":"166","author":"Djernes JK","year":"2004","journal-title":"Ugeskr Laeger"},{"key":"bibr17-25424823241289373","doi-asserted-by":"publisher","DOI":"10.5014\/ajot.53.5.471"},{"key":"bibr18-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1080\/08039480801985146"},{"key":"bibr19-25424823241289373","first-page":"28","volume":"4","author":"Busner J","year":"2007","journal-title":"Psychiatry (Edgmont)"},{"key":"bibr20-25424823241289373","unstructured":"European Medicines Agency. E6 (R2 \u2013 Step 5): Guideline Good Clinical Practice E6(R2) \u2013 Step 5.\n                      Committee for Human Medicinal Products\n                      ; 6, https:\/\/www.ema.europa.eu\/en\/ich-e6-r2-good-clinical-practice-scientific-guideline (accessed 14 September 2024)."},{"key":"bibr21-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2012.02.008"},{"key":"bibr22-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1821"},{"key":"bibr23-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"bibr24-25424823241289373","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160164"},{"key":"bibr25-25424823241289373","unstructured":"Eisai Co. Ltd. Aricept (donepezil hydrochloride) label.\n                      Highlights of prescribing information: Aricept (Donepezil hydrochloride tablets\n                      , https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2012\/020690s035,021720s008,022568s005lbl.pdf (accessed 14 September 2024)."},{"key":"bibr26-25424823241289373","first-page":"293","volume":"7","author":"Rogers SL","year":"1996","journal-title":"Dementia"},{"key":"bibr27-25424823241289373","volume":"6","author":"Birks JS","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"bibr28-25424823241289373","unstructured":"Bethesda. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury \u2013 Donepezil. In:\n                      LiverTox: Clinical and Research Information on Drug-Induced Liver Injury\n                      2020. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548197\/ (accessed September 14, 2024)."},{"key":"bibr29-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000645"},{"key":"bibr30-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-022-06068-x"},{"key":"bibr31-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.00535.x"},{"key":"bibr32-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14434"},{"key":"bibr33-25424823241289373","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220508"},{"key":"bibr34-25424823241289373","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(92)90246-V"}],"container-title":["Journal of Alzheimer's Disease Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/25424823241289373","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/25424823241289373","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/25424823241289373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:57:40Z","timestamp":1777370260000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/25424823241289373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1177\/25424823241289373"],"URL":"https:\/\/doi.org\/10.1177\/25424823241289373","relation":{},"ISSN":["2542-4823","2542-4823"],"issn-type":[{"value":"2542-4823","type":"print"},{"value":"2542-4823","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]}}}