Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial
IMPORTANCE: Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). OBJECTIVE: To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. DESIGN, SETTING, AND PARTICIPANTS: The Levetiracetam for Alzheimer...
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| creator | Vossel, Keith Ranasinghe, Kamalini G Beagle, Alexander J La, Alice Ah Pook, Kasey Castro, Madelyn Mizuiri, Danielle Honma, Susanne M Venkateswaran, Nisha Koestler, Mary Zhang, Wenbo Mucke, Lennart Howell, Michael J Possin, Katherine L Kramer, Joel H Boxer, Adam L Miller, Bruce L Nagarajan, Srikantan S Kirsch, Heidi E |
| description | IMPORTANCE: Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). OBJECTIVE: To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. DESIGN, SETTING, AND PARTICIPANTS: The Levetiracetam for Alzheimer’s Disease–Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. INTERVENTIONS: Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. MAIN OUTCOMES AND MEASURES: The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. RESULTS: Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, −0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levet |
| doi_str_mv | 10.1001/jamaneurol.2021.3310 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8477304</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><ama_id>2784539</ama_id><sourcerecordid>2576915530</sourcerecordid><originalsourceid>FETCH-LOGICAL-a358t-fd6a2bf011e32161d06adb3a35a8a4ed42d45221993bd1f8147cd4e954f63e933</originalsourceid><addsrcrecordid>eNpdkd-KEzEUxoMo7lL3BUQk4I03rckkmT9eCKVWd6GgyIqXIZ052Z6SmdQkU9h9BV_a1K513dzkkO93DufLR8grzmacMf5ua3ozwBi8mxWs4DMhOHtCzgte1tOSq-rpqZbNGbmIccvyqRmTQj4nZ0KqivGqOie_ltZCm6i3dAV7SBhMC8n01A904W8GTJgrHOhXkxCGFOkPTBs6d3cbwB4C_YgRTITjsxm6P4UfE13u0MEuofWhp_M24R7T7Xs6p98y5Xu8g44uHA7YGkevAxr3gjyzxkW4uL8n5Pun5fXicrr68vlqMV9NjVB1mtquNMXaMs5BZJO8Y6Xp1iKLpjYSOll0UhUFbxqx7rituazaTkKjpC0FNEJMyIfj3N247qFrs61gnN4F7E241d6g_l8ZcKNv_F7XsqpE_sIJeXs_IPifI8Ske4wtOJcz8WPUharKhislWEbfPEK3fgxDtpeppuaHLVWm5JFqg48xgD0tw5k-BK7_Ba4PgetD4Lnt9UMjp6a_8Wbg5RHI3Se1qGqpRCN-A93ftBY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2598119935</pqid></control><display><type>article</type><title>Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial</title><source>MEDLINE</source><source>American Medical Association Journals</source><creator>Vossel, Keith ; Ranasinghe, Kamalini G ; Beagle, Alexander J ; La, Alice ; Ah Pook, Kasey ; Castro, Madelyn ; Mizuiri, Danielle ; Honma, Susanne M ; Venkateswaran, Nisha ; Koestler, Mary ; Zhang, Wenbo ; Mucke, Lennart ; Howell, Michael J ; Possin, Katherine L ; Kramer, Joel H ; Boxer, Adam L ; Miller, Bruce L ; Nagarajan, Srikantan S ; Kirsch, Heidi E</creator><creatorcontrib>Vossel, Keith ; Ranasinghe, Kamalini G ; Beagle, Alexander J ; La, Alice ; Ah Pook, Kasey ; Castro, Madelyn ; Mizuiri, Danielle ; Honma, Susanne M ; Venkateswaran, Nisha ; Koestler, Mary ; Zhang, Wenbo ; Mucke, Lennart ; Howell, Michael J ; Possin, Katherine L ; Kramer, Joel H ; Boxer, Adam L ; Miller, Bruce L ; Nagarajan, Srikantan S ; Kirsch, Heidi E</creatorcontrib><description>IMPORTANCE: Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). OBJECTIVE: To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. DESIGN, SETTING, AND PARTICIPANTS: The Levetiracetam for Alzheimer’s Disease–Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. INTERVENTIONS: Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. MAIN OUTCOMES AND MEASURES: The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. RESULTS: Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, −0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, 0.2-14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = 0.11; P = .02). There were no treatment discontinuations because of adverse events. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02002819</description><identifier>ISSN: 2168-6149</identifier><identifier>EISSN: 2168-6157</identifier><identifier>DOI: 10.1001/jamaneurol.2021.3310</identifier><identifier>PMID: 34570177</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adults ; Adverse events ; Aged ; Aged, 80 and over ; Alzheimer Disease - complications ; Alzheimer Disease - drug therapy ; Alzheimer's disease ; Anticonvulsants - therapeutic use ; Clinical trials ; Cognition ; Cognition & reasoning ; Cognition - drug effects ; Cognitive ability ; Comments ; Cross-Over Studies ; Dementia disorders ; Double-Blind Method ; Drug development ; EEG ; Electroencephalography ; Epilepsy ; Etiracetam ; Executive function ; Executive Function - drug effects ; Exploratory behavior ; Female ; Functional testing ; Health services ; Humans ; Interference ; Learning ; Levetiracetam - therapeutic use ; Magnetoencephalography ; Male ; Memory tasks ; Middle Aged ; Naming ; Neurodegenerative diseases ; Online First ; Original Investigation ; Patients ; Placebos ; Seizures - etiology ; Spatial analysis ; Spatial memory</subject><ispartof>Archives of neurology (Chicago), 2021-11, Vol.78 (11), p.1345-1354</ispartof><rights>Copyright American Medical Association Nov 2021</rights><rights>Copyright 2021 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a358t-fd6a2bf011e32161d06adb3a35a8a4ed42d45221993bd1f8147cd4e954f63e933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamaneurology/articlepdf/10.1001/jamaneurol.2021.3310$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2021.3310$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,780,784,885,3331,27915,27916,76250,76253</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34570177$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vossel, Keith</creatorcontrib><creatorcontrib>Ranasinghe, Kamalini G</creatorcontrib><creatorcontrib>Beagle, Alexander J</creatorcontrib><creatorcontrib>La, Alice</creatorcontrib><creatorcontrib>Ah Pook, Kasey</creatorcontrib><creatorcontrib>Castro, Madelyn</creatorcontrib><creatorcontrib>Mizuiri, Danielle</creatorcontrib><creatorcontrib>Honma, Susanne M</creatorcontrib><creatorcontrib>Venkateswaran, Nisha</creatorcontrib><creatorcontrib>Koestler, Mary</creatorcontrib><creatorcontrib>Zhang, Wenbo</creatorcontrib><creatorcontrib>Mucke, Lennart</creatorcontrib><creatorcontrib>Howell, Michael J</creatorcontrib><creatorcontrib>Possin, Katherine L</creatorcontrib><creatorcontrib>Kramer, Joel H</creatorcontrib><creatorcontrib>Boxer, Adam L</creatorcontrib><creatorcontrib>Miller, Bruce L</creatorcontrib><creatorcontrib>Nagarajan, Srikantan S</creatorcontrib><creatorcontrib>Kirsch, Heidi E</creatorcontrib><title>Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial</title><title>Archives of neurology (Chicago)</title><addtitle>JAMA Neurol</addtitle><description>IMPORTANCE: Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). OBJECTIVE: To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. DESIGN, SETTING, AND PARTICIPANTS: The Levetiracetam for Alzheimer’s Disease–Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. INTERVENTIONS: Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. MAIN OUTCOMES AND MEASURES: The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. RESULTS: Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, −0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, 0.2-14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = 0.11; P = .02). There were no treatment discontinuations because of adverse events. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02002819</description><subject>Adults</subject><subject>Adverse events</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - complications</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer's disease</subject><subject>Anticonvulsants - therapeutic use</subject><subject>Clinical trials</subject><subject>Cognition</subject><subject>Cognition & reasoning</subject><subject>Cognition - drug effects</subject><subject>Cognitive ability</subject><subject>Comments</subject><subject>Cross-Over Studies</subject><subject>Dementia disorders</subject><subject>Double-Blind Method</subject><subject>Drug development</subject><subject>EEG</subject><subject>Electroencephalography</subject><subject>Epilepsy</subject><subject>Etiracetam</subject><subject>Executive function</subject><subject>Executive Function - drug effects</subject><subject>Exploratory behavior</subject><subject>Female</subject><subject>Functional testing</subject><subject>Health services</subject><subject>Humans</subject><subject>Interference</subject><subject>Learning</subject><subject>Levetiracetam - therapeutic use</subject><subject>Magnetoencephalography</subject><subject>Male</subject><subject>Memory tasks</subject><subject>Middle Aged</subject><subject>Naming</subject><subject>Neurodegenerative diseases</subject><subject>Online First</subject><subject>Original Investigation</subject><subject>Patients</subject><subject>Placebos</subject><subject>Seizures - etiology</subject><subject>Spatial analysis</subject><subject>Spatial memory</subject><issn>2168-6149</issn><issn>2168-6157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkd-KEzEUxoMo7lL3BUQk4I03rckkmT9eCKVWd6GgyIqXIZ052Z6SmdQkU9h9BV_a1K513dzkkO93DufLR8grzmacMf5ua3ozwBi8mxWs4DMhOHtCzgte1tOSq-rpqZbNGbmIccvyqRmTQj4nZ0KqivGqOie_ltZCm6i3dAV7SBhMC8n01A904W8GTJgrHOhXkxCGFOkPTBs6d3cbwB4C_YgRTITjsxm6P4UfE13u0MEuofWhp_M24R7T7Xs6p98y5Xu8g44uHA7YGkevAxr3gjyzxkW4uL8n5Pun5fXicrr68vlqMV9NjVB1mtquNMXaMs5BZJO8Y6Xp1iKLpjYSOll0UhUFbxqx7rituazaTkKjpC0FNEJMyIfj3N247qFrs61gnN4F7E241d6g_l8ZcKNv_F7XsqpE_sIJeXs_IPifI8Ske4wtOJcz8WPUharKhislWEbfPEK3fgxDtpeppuaHLVWm5JFqg48xgD0tw5k-BK7_Ba4PgetD4Lnt9UMjp6a_8Wbg5RHI3Se1qGqpRCN-A93ftBY</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Vossel, Keith</creator><creator>Ranasinghe, Kamalini G</creator><creator>Beagle, Alexander J</creator><creator>La, Alice</creator><creator>Ah Pook, Kasey</creator><creator>Castro, Madelyn</creator><creator>Mizuiri, Danielle</creator><creator>Honma, Susanne M</creator><creator>Venkateswaran, Nisha</creator><creator>Koestler, Mary</creator><creator>Zhang, Wenbo</creator><creator>Mucke, Lennart</creator><creator>Howell, Michael J</creator><creator>Possin, Katherine L</creator><creator>Kramer, Joel H</creator><creator>Boxer, Adam L</creator><creator>Miller, Bruce L</creator><creator>Nagarajan, Srikantan S</creator><creator>Kirsch, Heidi E</creator><general>American Medical Association</general><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>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20211101</creationdate><title>Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial</title><author>Vossel, Keith ; Ranasinghe, Kamalini G ; Beagle, Alexander J ; La, Alice ; Ah Pook, Kasey ; Castro, Madelyn ; Mizuiri, Danielle ; Honma, Susanne M ; Venkateswaran, Nisha ; Koestler, Mary ; Zhang, Wenbo ; Mucke, Lennart ; Howell, Michael J ; Possin, Katherine L ; Kramer, Joel H ; Boxer, Adam L ; Miller, Bruce L ; Nagarajan, Srikantan S ; Kirsch, Heidi E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a358t-fd6a2bf011e32161d06adb3a35a8a4ed42d45221993bd1f8147cd4e954f63e933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adults</topic><topic>Adverse events</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - complications</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer's disease</topic><topic>Anticonvulsants - therapeutic use</topic><topic>Clinical trials</topic><topic>Cognition</topic><topic>Cognition & reasoning</topic><topic>Cognition - drug effects</topic><topic>Cognitive ability</topic><topic>Comments</topic><topic>Cross-Over Studies</topic><topic>Dementia disorders</topic><topic>Double-Blind Method</topic><topic>Drug development</topic><topic>EEG</topic><topic>Electroencephalography</topic><topic>Epilepsy</topic><topic>Etiracetam</topic><topic>Executive function</topic><topic>Executive Function - drug effects</topic><topic>Exploratory behavior</topic><topic>Female</topic><topic>Functional testing</topic><topic>Health services</topic><topic>Humans</topic><topic>Interference</topic><topic>Learning</topic><topic>Levetiracetam - therapeutic use</topic><topic>Magnetoencephalography</topic><topic>Male</topic><topic>Memory tasks</topic><topic>Middle Aged</topic><topic>Naming</topic><topic>Neurodegenerative diseases</topic><topic>Online First</topic><topic>Original Investigation</topic><topic>Patients</topic><topic>Placebos</topic><topic>Seizures - etiology</topic><topic>Spatial analysis</topic><topic>Spatial memory</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vossel, Keith</creatorcontrib><creatorcontrib>Ranasinghe, Kamalini G</creatorcontrib><creatorcontrib>Beagle, Alexander J</creatorcontrib><creatorcontrib>La, Alice</creatorcontrib><creatorcontrib>Ah Pook, Kasey</creatorcontrib><creatorcontrib>Castro, Madelyn</creatorcontrib><creatorcontrib>Mizuiri, Danielle</creatorcontrib><creatorcontrib>Honma, Susanne M</creatorcontrib><creatorcontrib>Venkateswaran, Nisha</creatorcontrib><creatorcontrib>Koestler, Mary</creatorcontrib><creatorcontrib>Zhang, Wenbo</creatorcontrib><creatorcontrib>Mucke, Lennart</creatorcontrib><creatorcontrib>Howell, Michael J</creatorcontrib><creatorcontrib>Possin, Katherine L</creatorcontrib><creatorcontrib>Kramer, Joel H</creatorcontrib><creatorcontrib>Boxer, Adam L</creatorcontrib><creatorcontrib>Miller, Bruce L</creatorcontrib><creatorcontrib>Nagarajan, Srikantan S</creatorcontrib><creatorcontrib>Kirsch, Heidi E</creatorcontrib><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>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of neurology (Chicago)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vossel, Keith</au><au>Ranasinghe, Kamalini G</au><au>Beagle, Alexander J</au><au>La, Alice</au><au>Ah Pook, Kasey</au><au>Castro, Madelyn</au><au>Mizuiri, Danielle</au><au>Honma, Susanne M</au><au>Venkateswaran, Nisha</au><au>Koestler, Mary</au><au>Zhang, Wenbo</au><au>Mucke, Lennart</au><au>Howell, Michael J</au><au>Possin, Katherine L</au><au>Kramer, Joel H</au><au>Boxer, Adam L</au><au>Miller, Bruce L</au><au>Nagarajan, Srikantan S</au><au>Kirsch, Heidi E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial</atitle><jtitle>Archives of neurology (Chicago)</jtitle><addtitle>JAMA Neurol</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>78</volume><issue>11</issue><spage>1345</spage><epage>1354</epage><pages>1345-1354</pages><issn>2168-6149</issn><eissn>2168-6157</eissn><abstract>IMPORTANCE: Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). OBJECTIVE: To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. DESIGN, SETTING, AND PARTICIPANTS: The Levetiracetam for Alzheimer’s Disease–Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. INTERVENTIONS: Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. MAIN OUTCOMES AND MEASURES: The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. RESULTS: Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, −0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, 0.2-14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = 0.11; P = .02). There were no treatment discontinuations because of adverse events. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02002819</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>34570177</pmid><doi>10.1001/jamaneurol.2021.3310</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 2168-6149 |
| ispartof | Archives of neurology (Chicago), 2021-11, Vol.78 (11), p.1345-1354 |
| issn | 2168-6149 2168-6157 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8477304 |
| source | MEDLINE; American Medical Association Journals |
| subjects | Adults Adverse events Aged Aged, 80 and over Alzheimer Disease - complications Alzheimer Disease - drug therapy Alzheimer's disease Anticonvulsants - therapeutic use Clinical trials Cognition Cognition & reasoning Cognition - drug effects Cognitive ability Comments Cross-Over Studies Dementia disorders Double-Blind Method Drug development EEG Electroencephalography Epilepsy Etiracetam Executive function Executive Function - drug effects Exploratory behavior Female Functional testing Health services Humans Interference Learning Levetiracetam - therapeutic use Magnetoencephalography Male Memory tasks Middle Aged Naming Neurodegenerative diseases Online First Original Investigation Patients Placebos Seizures - etiology Spatial analysis Spatial memory |
| title | Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T18%3A27%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20Levetiracetam%20on%20Cognition%20in%20Patients%20With%20Alzheimer%20Disease%20With%20and%20Without%20Epileptiform%20Activity:%20A%20Randomized%20Clinical%20Trial&rft.jtitle=Archives%20of%20neurology%20(Chicago)&rft.au=Vossel,%20Keith&rft.date=2021-11-01&rft.volume=78&rft.issue=11&rft.spage=1345&rft.epage=1354&rft.pages=1345-1354&rft.issn=2168-6149&rft.eissn=2168-6157&rft_id=info:doi/10.1001/jamaneurol.2021.3310&rft_dat=%3Cproquest_pubme%3E2576915530%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2598119935&rft_id=info:pmid/34570177&rft_ama_id=2784539&rfr_iscdi=true |