Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial
Objective: Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double‐blind, placebo‐controlled exploratory phase 2 trial. Methods: One‐hundred forty patients with DLB,...
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| Veröffentlicht in: | Annals of neurology 2012-07, Vol.72 (1), p.41-52 |
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| container_title | Annals of neurology |
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| creator | Mori, Etsuro Ikeda, Manabu Kosaka, Kenji |
| description | Objective:
Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double‐blind, placebo‐controlled exploratory phase 2 trial.
Methods:
One‐hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini‐Mental State Examination (MMSE) and several domain‐specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview‐Based Impression of Change‐plus Caregiver Input (CIBIC‐plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III.
Results:
Donepezil at 5 and 10mg/day was significantly superior to placebo on both the MMSE (5mg: mean difference, 3.8; 95% confidence interval [CI], 2.3–5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9–3.9; p = 0.001) and CIBIC‐plus (p < 0.001 for each); 3mg/day was significantly superior to placebo on CIBIC‐plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups.
Interpretation:
Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated. ANN NEUROL 2012;72:41–52 |
| doi_str_mv | 10.1002/ana.23557 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3504981</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3282822091</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5447-6cde3817b99e4b7f976dd78a6e39b5f72af2563606736581fec8369769b735f93</originalsourceid><addsrcrecordid>eNp1kUtvEzEUhS0EoiGw4A-gkRASSEzrx_jFAikKUB5RKyGgEhvLM3OHunjGwZ4Q0l-PadLwkNjYC3_33ONzELpP8CHBmB7ZwR5Sxrm8gSaEM1IqWumbaIKZqEpOWHWA7qR0gTHWguDb6IBSRTUVaoJOX4QBlnDpfNGFWLTQwzA6W6zdeF4sYL0p6tA6SM-KWRHt0IbeXUL7tFh620AdyiYMYwzeQ1uM0Vl_F93qrE9wb3dP0cdXLz_MX5eL0-M389mibHhVyVI0LTBFZK01VLXstBRtK5UVwHTNO0ltR7lgAgvJBFekg0YxkSldS8Y7zabo-VZ3uap7aJvsOlpvltH1Nm5MsM78_TK4c_MlfDeM40orkgUe7wRi-LaCNJrepQa8twOEVTKEU8yUkvmcoof_oBdhFYf8vUwRxbPJK8EnW6qJIaUI3d4MweZXTSbXZK5qyuyDP93vyeteMvBoB9jUWN_l6BuXfnOC6JyOyNzRlls7D5v_bzSzk9n16nI74dIIP_YTNn41OWvJzdnJsTn7TN6KT-_fmTn7CeK9t4M</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1518506781</pqid></control><display><type>article</type><title>Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Mori, Etsuro ; Ikeda, Manabu ; Kosaka, Kenji</creator><creatorcontrib>Mori, Etsuro ; Ikeda, Manabu ; Kosaka, Kenji ; Donepezil-DLB Study Investigators ; on behalf of the Donepezil‐DLB Study Investigators</creatorcontrib><description>Objective:
Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double‐blind, placebo‐controlled exploratory phase 2 trial.
Methods:
One‐hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini‐Mental State Examination (MMSE) and several domain‐specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview‐Based Impression of Change‐plus Caregiver Input (CIBIC‐plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III.
Results:
Donepezil at 5 and 10mg/day was significantly superior to placebo on both the MMSE (5mg: mean difference, 3.8; 95% confidence interval [CI], 2.3–5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9–3.9; p = 0.001) and CIBIC‐plus (p < 0.001 for each); 3mg/day was significantly superior to placebo on CIBIC‐plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups.
Interpretation:
Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated. ANN NEUROL 2012;72:41–52</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.23557</identifier><identifier>PMID: 22829268</identifier><identifier>CODEN: ANNED3</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Aged ; Aged, 80 and over ; Behavior ; Biological and medical sciences ; Caregivers ; Cholinesterase Inhibitors - pharmacology ; Cholinesterase Inhibitors - therapeutic use ; Cognition - drug effects ; Confidence intervals ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Double-Blind Method ; Female ; Humans ; Indans - pharmacology ; Indans - therapeutic use ; Lewy Body Disease - drug therapy ; Lewy Body Disease - psychology ; Male ; Medical sciences ; Neurology ; Neuropsychological Tests ; Nootropic Agents - pharmacology ; Nootropic Agents - therapeutic use ; Older people ; Original ; Parkinson's disease ; Piperidines - pharmacology ; Piperidines - therapeutic use ; Severity of Illness Index ; Treatment Outcome</subject><ispartof>Annals of neurology, 2012-07, Vol.72 (1), p.41-52</ispartof><rights>Copyright © 2012 American Neurological Association</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 American Neurological Association.</rights><rights>2012 American Neurological Association 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5447-6cde3817b99e4b7f976dd78a6e39b5f72af2563606736581fec8369769b735f93</citedby><cites>FETCH-LOGICAL-c5447-6cde3817b99e4b7f976dd78a6e39b5f72af2563606736581fec8369769b735f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.23557$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.23557$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26196366$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22829268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mori, Etsuro</creatorcontrib><creatorcontrib>Ikeda, Manabu</creatorcontrib><creatorcontrib>Kosaka, Kenji</creatorcontrib><creatorcontrib>Donepezil-DLB Study Investigators</creatorcontrib><creatorcontrib>on behalf of the Donepezil‐DLB Study Investigators</creatorcontrib><title>Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective:
Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double‐blind, placebo‐controlled exploratory phase 2 trial.
Methods:
One‐hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini‐Mental State Examination (MMSE) and several domain‐specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview‐Based Impression of Change‐plus Caregiver Input (CIBIC‐plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III.
Results:
Donepezil at 5 and 10mg/day was significantly superior to placebo on both the MMSE (5mg: mean difference, 3.8; 95% confidence interval [CI], 2.3–5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9–3.9; p = 0.001) and CIBIC‐plus (p < 0.001 for each); 3mg/day was significantly superior to placebo on CIBIC‐plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups.
Interpretation:
Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated. ANN NEUROL 2012;72:41–52</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Behavior</subject><subject>Biological and medical sciences</subject><subject>Caregivers</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Cholinesterase Inhibitors - therapeutic use</subject><subject>Cognition - drug effects</subject><subject>Confidence intervals</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Humans</subject><subject>Indans - pharmacology</subject><subject>Indans - therapeutic use</subject><subject>Lewy Body Disease - drug therapy</subject><subject>Lewy Body Disease - psychology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neuropsychological Tests</subject><subject>Nootropic Agents - pharmacology</subject><subject>Nootropic Agents - therapeutic use</subject><subject>Older people</subject><subject>Original</subject><subject>Parkinson's disease</subject><subject>Piperidines - pharmacology</subject><subject>Piperidines - therapeutic use</subject><subject>Severity of Illness Index</subject><subject>Treatment Outcome</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kUtvEzEUhS0EoiGw4A-gkRASSEzrx_jFAikKUB5RKyGgEhvLM3OHunjGwZ4Q0l-PadLwkNjYC3_33ONzELpP8CHBmB7ZwR5Sxrm8gSaEM1IqWumbaIKZqEpOWHWA7qR0gTHWguDb6IBSRTUVaoJOX4QBlnDpfNGFWLTQwzA6W6zdeF4sYL0p6tA6SM-KWRHt0IbeXUL7tFh620AdyiYMYwzeQ1uM0Vl_F93qrE9wb3dP0cdXLz_MX5eL0-M389mibHhVyVI0LTBFZK01VLXstBRtK5UVwHTNO0ltR7lgAgvJBFekg0YxkSldS8Y7zabo-VZ3uap7aJvsOlpvltH1Nm5MsM78_TK4c_MlfDeM40orkgUe7wRi-LaCNJrepQa8twOEVTKEU8yUkvmcoof_oBdhFYf8vUwRxbPJK8EnW6qJIaUI3d4MweZXTSbXZK5qyuyDP93vyeteMvBoB9jUWN_l6BuXfnOC6JyOyNzRlls7D5v_bzSzk9n16nI74dIIP_YTNn41OWvJzdnJsTn7TN6KT-_fmTn7CeK9t4M</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Mori, Etsuro</creator><creator>Ikeda, Manabu</creator><creator>Kosaka, Kenji</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>24P</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>5PM</scope></search><sort><creationdate>201207</creationdate><title>Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial</title><author>Mori, Etsuro ; Ikeda, Manabu ; Kosaka, Kenji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5447-6cde3817b99e4b7f976dd78a6e39b5f72af2563606736581fec8369769b735f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Behavior</topic><topic>Biological and medical sciences</topic><topic>Caregivers</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Cholinesterase Inhibitors - therapeutic use</topic><topic>Cognition - drug effects</topic><topic>Confidence intervals</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Humans</topic><topic>Indans - pharmacology</topic><topic>Indans - therapeutic use</topic><topic>Lewy Body Disease - drug therapy</topic><topic>Lewy Body Disease - psychology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neuropsychological Tests</topic><topic>Nootropic Agents - pharmacology</topic><topic>Nootropic Agents - therapeutic use</topic><topic>Older people</topic><topic>Original</topic><topic>Parkinson's disease</topic><topic>Piperidines - pharmacology</topic><topic>Piperidines - therapeutic use</topic><topic>Severity of Illness Index</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mori, Etsuro</creatorcontrib><creatorcontrib>Ikeda, Manabu</creatorcontrib><creatorcontrib>Kosaka, Kenji</creatorcontrib><creatorcontrib>Donepezil-DLB Study Investigators</creatorcontrib><creatorcontrib>on behalf of the Donepezil‐DLB Study Investigators</creatorcontrib><collection>Istex</collection><collection>Wiley Online Library Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mori, Etsuro</au><au>Ikeda, Manabu</au><au>Kosaka, Kenji</au><aucorp>Donepezil-DLB Study Investigators</aucorp><aucorp>on behalf of the Donepezil‐DLB Study Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2012-07</date><risdate>2012</risdate><volume>72</volume><issue>1</issue><spage>41</spage><epage>52</epage><pages>41-52</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><coden>ANNED3</coden><abstract>Objective:
Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double‐blind, placebo‐controlled exploratory phase 2 trial.
Methods:
One‐hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini‐Mental State Examination (MMSE) and several domain‐specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview‐Based Impression of Change‐plus Caregiver Input (CIBIC‐plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III.
Results:
Donepezil at 5 and 10mg/day was significantly superior to placebo on both the MMSE (5mg: mean difference, 3.8; 95% confidence interval [CI], 2.3–5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9–3.9; p = 0.001) and CIBIC‐plus (p < 0.001 for each); 3mg/day was significantly superior to placebo on CIBIC‐plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups.
Interpretation:
Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated. ANN NEUROL 2012;72:41–52</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22829268</pmid><doi>10.1002/ana.23557</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Annals of neurology, 2012-07, Vol.72 (1), p.41-52 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aged Aged, 80 and over Behavior Biological and medical sciences Caregivers Cholinesterase Inhibitors - pharmacology Cholinesterase Inhibitors - therapeutic use Cognition - drug effects Confidence intervals Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Double-Blind Method Female Humans Indans - pharmacology Indans - therapeutic use Lewy Body Disease - drug therapy Lewy Body Disease - psychology Male Medical sciences Neurology Neuropsychological Tests Nootropic Agents - pharmacology Nootropic Agents - therapeutic use Older people Original Parkinson's disease Piperidines - pharmacology Piperidines - therapeutic use Severity of Illness Index Treatment Outcome |
| title | Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial |
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