Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia
Identifieur interne : 000918 ( Pmc/Checkpoint ); précédent : 000917; suivant : 000919Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia
Auteurs : Tiffany W. Chow [Canada] ; Ariel Graff-Guerrero [Canada] ; Nicolaas Plg Verhoeff [Canada] ; Malcolm A. Binns [Canada] ; David F. Tang-Wai [Canada] ; Morris Freedman [Canada] ; Mario Masellis [Canada] ; Sandra E. Black [Canada] ; Alan A. Wilson [Canada] ; Sylvain Houle [Canada] ; Bruce G. Pollock [Canada]Source :
- Neuropsychiatric Disease and Treatment [ 1176-6328 ] ; 2011.
Abstract
Memantine has shown effects on cortical metabolism in Alzheimer’s disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.
Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.
Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [18F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (
This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.
Url:
DOI: 10.2147/NDT.S22635
PubMed: 21792308
PubMed Central: 3140294
Affiliations:
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Chow</name><affiliation><nlm:aff id="af1-ndt-7-415"> Division of Neurology, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af2-ndt-7-415"> Department of Psychiatry, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Graff Guerrero, Ariel" sort="Graff Guerrero, Ariel" uniqKey="Graff Guerrero A" first="Ariel" last="Graff-Guerrero">Ariel Graff-Guerrero</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Verhoeff, Nicolaas Plg" sort="Verhoeff, Nicolaas Plg" uniqKey="Verhoeff N" first="Nicolaas Plg" last="Verhoeff">Nicolaas Plg Verhoeff</name><affiliation><nlm:aff id="af2-ndt-7-415"> Department of Psychiatry, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af7-ndt-7-415"> Kunin-Lunenfeld Applied Research Unit, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation></author><author><name sortKey="Binns, Malcolm A" sort="Binns, Malcolm A" uniqKey="Binns M" first="Malcolm A" last="Binns">Malcolm A. Binns</name><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af8-ndt-7-415"> Dalla Lana School of Public Health, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Tang Wai, David F" sort="Tang Wai, David F" uniqKey="Tang Wai D" first="David F" last="Tang-Wai">David F. Tang-Wai</name><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af9-ndt-7-415"> University Health Network Memory Clinic</nlm:aff></affiliation></author><author><name sortKey="Freedman, Morris" sort="Freedman, Morris" uniqKey="Freedman M" first="Morris" last="Freedman">Morris Freedman</name><affiliation><nlm:aff id="af1-ndt-7-415"> Division of Neurology, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Masellis, Mario" sort="Masellis, Mario" uniqKey="Masellis M" first="Mario" last="Masellis">Mario Masellis</name><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="af10-ndt-7-415"> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Black, Sandra E" sort="Black, Sandra E" uniqKey="Black S" first="Sandra E" last="Black">Sandra E. Black</name><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="af10-ndt-7-415"> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Wilson, Alan A" sort="Wilson, Alan A" uniqKey="Wilson A" first="Alan A" last="Wilson">Alan A. Wilson</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Pollock, Bruce G" sort="Pollock, Bruce G" uniqKey="Pollock B" first="Bruce G" last="Pollock">Bruce G. Pollock</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21792308</idno><idno type="pmc">3140294</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140294</idno><idno type="RBID">PMC:3140294</idno><idno type="doi">10.2147/NDT.S22635</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000A56</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A56</idno><idno type="wicri:Area/Pmc/Curation">000A56</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A56</idno><idno type="wicri:Area/Pmc/Checkpoint">000918</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000918</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia</title><author><name sortKey="Chow, Tiffany W" sort="Chow, Tiffany W" uniqKey="Chow T" first="Tiffany W" last="Chow">Tiffany W. Chow</name><affiliation><nlm:aff id="af1-ndt-7-415"> Division of Neurology, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af2-ndt-7-415"> Department of Psychiatry, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Graff Guerrero, Ariel" sort="Graff Guerrero, Ariel" uniqKey="Graff Guerrero A" first="Ariel" last="Graff-Guerrero">Ariel Graff-Guerrero</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Verhoeff, Nicolaas Plg" sort="Verhoeff, Nicolaas Plg" uniqKey="Verhoeff N" first="Nicolaas Plg" last="Verhoeff">Nicolaas Plg Verhoeff</name><affiliation><nlm:aff id="af2-ndt-7-415"> Department of Psychiatry, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af7-ndt-7-415"> Kunin-Lunenfeld Applied Research Unit, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation></author><author><name sortKey="Binns, Malcolm A" sort="Binns, Malcolm A" uniqKey="Binns M" first="Malcolm A" last="Binns">Malcolm A. Binns</name><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af8-ndt-7-415"> Dalla Lana School of Public Health, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Tang Wai, David F" sort="Tang Wai, David F" uniqKey="Tang Wai D" first="David F" last="Tang-Wai">David F. Tang-Wai</name><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af9-ndt-7-415"> University Health Network Memory Clinic</nlm:aff></affiliation></author><author><name sortKey="Freedman, Morris" sort="Freedman, Morris" uniqKey="Freedman M" first="Morris" last="Freedman">Morris Freedman</name><affiliation><nlm:aff id="af1-ndt-7-415"> Division of Neurology, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Masellis, Mario" sort="Masellis, Mario" uniqKey="Masellis M" first="Mario" last="Masellis">Mario Masellis</name><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="af10-ndt-7-415"> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Black, Sandra E" sort="Black, Sandra E" uniqKey="Black S" first="Sandra E" last="Black">Sandra E. Black</name><affiliation><nlm:aff id="af3-ndt-7-415"> Rotman Research Institute, Baycrest</nlm:aff><wicri:noCountry code="subfield">Baycrest</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="af5-ndt-7-415"> Department of Medicine, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="af10-ndt-7-415"> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Wilson, Alan A" sort="Wilson, Alan A" uniqKey="Wilson A" first="Alan A" last="Wilson">Alan A. Wilson</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author><author><name sortKey="Pollock, Bruce G" sort="Pollock, Bruce G" uniqKey="Pollock B" first="Bruce G" last="Pollock">Bruce G. Pollock</name><affiliation wicri:level="4"><nlm:aff id="af4-ndt-7-415"> Department of Psychiatry, Division of Neurology, University of Toronto</nlm:aff><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation><nlm:aff id="af6-ndt-7-415"> Centre for Addiction and Mental Health PET Centre</nlm:aff></affiliation></author></analytic><series><title level="j">Neuropsychiatric Disease and Treatment</title><idno type="ISSN">1176-6328</idno><idno type="eISSN">1178-2021</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Memantine has shown effects on cortical metabolism in Alzheimer’s disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.</p></sec><sec><title>Methods</title><p>Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.</p></sec><sec><title>Results</title><p>Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [<sup>18</sup>F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (<italic>P</italic> < 0.01). The increase on FDG-PET did not correlate with changes on behavioral inventories. Post hoc analysis indicated that semantic dementia participants drove this finding.</p></sec><sec><title>Conclusion</title><p>This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chow, Tw" uniqKey="Chow T">TW Chow</name></author><author><name sortKey="Hynan, Ls" uniqKey="Hynan L">LS Hynan</name></author><author><name sortKey="Lipton, Am" uniqKey="Lipton A">AM Lipton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Caycedo, Am" uniqKey="Caycedo A">AM Caycedo</name></author><author><name sortKey="Miller, B" uniqKey="Miller B">B Miller</name></author><author><name sortKey="Kramer, J" uniqKey="Kramer J">J Kramer</name></author><author><name sortKey="Rascovsky, K" uniqKey="Rascovsky K">K Rascovsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gorno Tempini, Ml" uniqKey="Gorno Tempini M">ML Gorno-Tempini</name></author><author><name sortKey="Hillis, Ae" uniqKey="Hillis A">AE Hillis</name></author><author><name sortKey="Weintraub, S" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Neuropsychiatr Dis Treat</journal-id><journal-id journal-id-type="publisher-id">Neuropsychiatric Disease and Treatment</journal-id><journal-title-group><journal-title>Neuropsychiatric Disease and Treatment</journal-title></journal-title-group><issn pub-type="ppub">1176-6328</issn><issn pub-type="epub">1178-2021</issn><publisher><publisher-name>Dove Medical Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21792308</article-id><article-id pub-id-type="pmc">3140294</article-id><article-id pub-id-type="doi">10.2147/NDT.S22635</article-id><article-id pub-id-type="publisher-id">ndt-7-415</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject></subj-group></article-categories><title-group><article-title>Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chow</surname><given-names>Tiffany W</given-names></name><xref ref-type="aff" rid="af1-ndt-7-415">1</xref><xref ref-type="aff" rid="af2-ndt-7-415">2</xref><xref ref-type="aff" rid="af3-ndt-7-415">3</xref><xref ref-type="aff" rid="af4-ndt-7-415">4</xref><xref ref-type="aff" rid="af5-ndt-7-415">5</xref><xref ref-type="aff" rid="af6-ndt-7-415">6</xref><xref ref-type="corresp" rid="c1-ndt-7-415"></xref></contrib><contrib contrib-type="author"><name><surname>Graff-Guerrero</surname><given-names>Ariel</given-names></name><xref ref-type="aff" rid="af4-ndt-7-415">4</xref><xref ref-type="aff" rid="af6-ndt-7-415">6</xref></contrib><contrib contrib-type="author"><name><surname>Verhoeff</surname><given-names>Nicolaas PLG</given-names></name><xref ref-type="aff" rid="af2-ndt-7-415">2</xref><xref ref-type="aff" rid="af3-ndt-7-415">3</xref><xref ref-type="aff" rid="af4-ndt-7-415">4</xref><xref ref-type="aff" rid="af7-ndt-7-415">7</xref></contrib><contrib contrib-type="author"><name><surname>Binns</surname><given-names>Malcolm A</given-names></name><xref ref-type="aff" rid="af3-ndt-7-415">3</xref><xref ref-type="aff" rid="af8-ndt-7-415">8</xref></contrib><contrib contrib-type="author"><name><surname>Tang-Wai</surname><given-names>David F</given-names></name><xref ref-type="aff" rid="af5-ndt-7-415">5</xref><xref ref-type="aff" rid="af9-ndt-7-415">9</xref></contrib><contrib contrib-type="author"><name><surname>Freedman</surname><given-names>Morris</given-names></name><xref ref-type="aff" rid="af1-ndt-7-415">1</xref><xref ref-type="aff" rid="af3-ndt-7-415">3</xref><xref ref-type="aff" rid="af5-ndt-7-415">5</xref></contrib><contrib contrib-type="author"><name><surname>Masellis</surname><given-names>Mario</given-names></name><xref ref-type="aff" rid="af5-ndt-7-415">5</xref><xref ref-type="aff" rid="af10-ndt-7-415">10</xref></contrib><contrib contrib-type="author"><name><surname>Black</surname><given-names>Sandra E</given-names></name><xref ref-type="aff" rid="af3-ndt-7-415">3</xref><xref ref-type="aff" rid="af5-ndt-7-415">5</xref><xref ref-type="aff" rid="af10-ndt-7-415">10</xref></contrib><contrib contrib-type="author"><name><surname>Wilson</surname><given-names>Alan A</given-names></name><xref ref-type="aff" rid="af4-ndt-7-415">4</xref><xref ref-type="aff" rid="af6-ndt-7-415">6</xref></contrib><contrib contrib-type="author"><name><surname>Houle</surname><given-names>Sylvain</given-names></name><xref ref-type="aff" rid="af4-ndt-7-415">4</xref><xref ref-type="aff" rid="af6-ndt-7-415">6</xref></contrib><contrib contrib-type="author"><name><surname>Pollock</surname><given-names>Bruce G</given-names></name><xref ref-type="aff" rid="af4-ndt-7-415">4</xref><xref ref-type="aff" rid="af6-ndt-7-415">6</xref></contrib></contrib-group><aff id="af1-ndt-7-415"><label>1</label> Division of Neurology, Baycrest</aff><aff id="af2-ndt-7-415"><label>2</label> Department of Psychiatry, Baycrest</aff><aff id="af3-ndt-7-415"><label>3</label> Rotman Research Institute, Baycrest</aff><aff id="af4-ndt-7-415"><label>4</label> Department of Psychiatry, Division of Neurology, University of Toronto</aff><aff id="af5-ndt-7-415"><label>5</label> Department of Medicine, Division of Neurology, University of Toronto</aff><aff id="af6-ndt-7-415"><label>6</label> Centre for Addiction and Mental Health PET Centre</aff><aff id="af7-ndt-7-415"><label>7</label> Kunin-Lunenfeld Applied Research Unit, Baycrest</aff><aff id="af8-ndt-7-415"><label>8</label> Dalla Lana School of Public Health, University of Toronto</aff><aff id="af9-ndt-7-415"><label>9</label> University Health Network Memory Clinic</aff><aff id="af10-ndt-7-415"><label>10</label> LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON, Canada</aff><author-notes><corresp id="c1-ndt-7-415">Correspondence: Tiffany Chow, Rotman Research Institute, Baycrest Brain Health Complex, 3560 Bathurst Street, Toronto, ON, M6A 2E1, Canada, Tel +1 416 785 2500 extn 3459, Fax +1 416 785 2862, Email <email>tchow@rotman-baycrest.on.ca</email></corresp></author-notes><pub-date pub-type="collection"><year>2011</year></pub-date><pmc-comment>Dove Press titles changed from ppub to collections in 2009.
Fake ppub written to satisfy Coll Date Type=ppub</pmc-comment>
<pub-date pub-type="ppub"><year>2011</year></pub-date><pub-date pub-type="epub"><day>13</day><month>7</month><year>2011</year></pub-date><volume>7</volume><fpage>415</fpage><lpage>424</lpage><permissions><copyright-statement>© 2011 Chow et al, publisher and licensee Dove Medical Press Ltd.</copyright-statement><copyright-year>2011</copyright-year><license><license-p>This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.</license-p></license></permissions><abstract><sec><title>Background</title><p>Memantine has shown effects on cortical metabolism in Alzheimer’s disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.</p></sec><sec><title>Methods</title><p>Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.</p></sec><sec><title>Results</title><p>Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [<sup>18</sup>F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (<italic>P</italic> < 0.01). The increase on FDG-PET did not correlate with changes on behavioral inventories. Post hoc analysis indicated that semantic dementia participants drove this finding.</p></sec><sec><title>Conclusion</title><p>This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.</p></sec></abstract><kwd-group><kwd>Alzheimer’s disease</kwd><kwd>frontotemporal dementia</kwd><kwd>metabolism</kwd><kwd>PET scan</kwd><kwd>semantic dementia</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-ndt-7-415" position="float"><label>Figure 1</label><caption><p>Flowchart for recruitment, including early withdrawals.</p></caption><graphic xlink:href="ndt-7-415f1"></graphic></fig><fig id="f2-ndt-7-415" position="float"><label>Figure 2</label><caption><p>Clusters of at least 10 voxels in bilateral insulae and left orbitofrontal cortex where the t-contrast for increase between baseline and 2-month FDG-PET normalized metabolic activity had <italic>P</italic> values <0.01. Color bars indicate <italic>t</italic> statistic values. Volumes of interest are shown on the T1-weighted template created from the average of all 16 participants with frontotemporal atrophy in the MNI space.</p><p> <bold>Abbreviation:</bold> MNI, Montreal Neurological Institute.</p></caption><graphic xlink:href="ndt-7-415f2"></graphic></fig><table-wrap id="t1-ndt-7-415" position="float"><label>Table 1</label><caption><p>Demographics and clinical measures for 16 participants after 2 months of memantine, in descending order of [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography normalized metabolic activity in the right insula by group. Participants in bold font had percentage change in normalized metabolic activity greater than 3.0. One additional participant with progressive nonfluent aphasia completed the study, ie, a man aged 59 years, who entered the study 2 years into his illness</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="2" colspan="1">Patient ID</th><th align="left" valign="top" rowspan="2" colspan="1">M/F</th><th align="left" valign="top" rowspan="2" colspan="1">Onset age</th><th align="left" valign="top" rowspan="2" colspan="1">Illness duration (years)</th><th colspan="3" align="left" valign="top" rowspan="1">% Change in normalized metabolic activity
<hr></hr></th></tr><tr><th align="left" valign="top" rowspan="1" colspan="1">Right insula</th><th align="left" valign="top" rowspan="1" colspan="1">Left insula</th><th align="left" valign="top" rowspan="1" colspan="1">Left OFC</th></tr></thead><tbody><tr><td colspan="7" align="left" valign="top" rowspan="1"><bold>Behavioral variant FTD</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>018</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>M</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>66</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>8</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>10.89</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>6.10</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>10.88</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>003</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>F</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>65</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>5</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>5.72</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>5.75</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>4.89</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>007</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>M</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>51</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>6</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>4.46</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>4.27</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>7.49</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>026</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>F</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>66</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>1</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>3.70</bold></td><td align="right" valign="top" rowspan="1" colspan="1">1.33</td><td align="right" valign="top" rowspan="1" colspan="1">7.75</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">020</td><td align="left" valign="top" rowspan="1" colspan="1">M</td><td align="left" valign="top" rowspan="1" colspan="1">55</td><td align="left" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">2.57</td><td align="right" valign="top" rowspan="1" colspan="1"><bold>5.45</bold></td><td align="right" valign="top" rowspan="1" colspan="1">2.99</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">004</td><td align="left" valign="top" rowspan="1" colspan="1">M</td><td align="left" valign="top" rowspan="1" colspan="1">58</td><td align="left" valign="top" rowspan="1" colspan="1">11</td><td align="center" valign="top" rowspan="1" colspan="1">2.29</td><td align="right" valign="top" rowspan="1" colspan="1">2.98</td><td align="right" valign="top" rowspan="1" colspan="1"><bold>4.04</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">006</td><td align="left" valign="top" rowspan="1" colspan="1">F</td><td align="left" valign="top" rowspan="1" colspan="1">66</td><td align="left" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">−0.34</td><td align="right" valign="top" rowspan="1" colspan="1">−0.09</td><td align="right" valign="top" rowspan="1" colspan="1">0.20</td></tr><tr><td colspan="7" align="left" valign="top" rowspan="1"><bold>Semantic dementia</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>019</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>M</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>59</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>6.58</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>9.41</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>12.86</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>028</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>F</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>57</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>5.03</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>4.54</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>4.10</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>015</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>M</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>69</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>3.71</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>6.10</bold></td><td align="right" valign="top" rowspan="1" colspan="1"><bold>4.58</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">002</td><td align="left" valign="top" rowspan="1" colspan="1">M</td><td align="left" valign="top" rowspan="1" colspan="1">47</td><td align="left" valign="top" rowspan="1" colspan="1">6</td><td align="center" valign="top" rowspan="1" colspan="1">1.42</td><td align="right" valign="top" rowspan="1" colspan="1">0.12</td><td align="right" valign="top" rowspan="1" colspan="1">0.19</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">021</td><td align="left" valign="top" rowspan="1" colspan="1">F</td><td align="left" valign="top" rowspan="1" colspan="1">62</td><td align="left" valign="top" rowspan="1" colspan="1">5</td><td align="center" valign="top" rowspan="1" colspan="1">1.04</td><td align="right" valign="top" rowspan="1" colspan="1">0.78</td><td align="right" valign="top" rowspan="1" colspan="1">2.46</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">022</td><td align="left" valign="top" rowspan="1" colspan="1">M</td><td align="left" valign="top" rowspan="1" colspan="1">74</td><td align="left" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">0.97</td><td align="right" valign="top" rowspan="1" colspan="1">1.03</td><td align="right" valign="top" rowspan="1" colspan="1">0.11</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">011</td><td align="left" valign="top" rowspan="1" colspan="1">F</td><td align="left" valign="top" rowspan="1" colspan="1">54</td><td align="left" valign="top" rowspan="1" colspan="1">4</td><td align="center" valign="top" rowspan="1" colspan="1">−0.4</td><td align="right" valign="top" rowspan="1" colspan="1">−2.72</td><td align="right" valign="top" rowspan="1" colspan="1"><bold>3.23</bold></td></tr><tr><td colspan="7" align="left" valign="top" rowspan="1"><bold>Progressive nonfluent aphasia</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">016</td><td align="left" valign="top" rowspan="1" colspan="1"><bold>M</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>57</bold></td><td align="left" valign="top" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" valign="top" rowspan="1" colspan="1"><bold>3.75</bold></td><td align="right" valign="top" rowspan="1" colspan="1">2.00</td><td align="right" valign="top" rowspan="1" colspan="1">0.54</td></tr></tbody></table><table-wrap-foot><fn id="tfn1-ndt-7-415"><p><bold>Abbreviations:</bold> FTD, frontotemporal dementia; OFC, orbitofrontal cortex.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t2-ndt-7-415" position="float"><label>Table 2</label><caption><p>Regions with increased normalized metabolic activity</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="2" colspan="1">Voxel of interest</th><th colspan="3" align="left" valign="top" rowspan="1">Peak voxel coordinates</th><th align="left" valign="top" rowspan="2" colspan="1">Cluster size</th><th align="left" valign="top" rowspan="2" colspan="1">Uncorrected voxel <italic>P</italic> value</th><th align="left" valign="top" rowspan="2" colspan="1">False discovery rate-corrected <italic>P</italic> value for small volume adjustment</th><th align="left" valign="top" rowspan="2" colspan="1">Mean change in normalized metabolic activity</th><th align="left" valign="top" rowspan="2" colspan="1">Paired <italic>t</italic>-statistic</th><th align="left" valign="top" rowspan="2" colspan="1">95% CI</th></tr><tr><th align="center" valign="top" rowspan="1" colspan="1">x</th><th align="center" valign="top" rowspan="1" colspan="1">y</th><th align="center" valign="top" rowspan="1" colspan="1">z</th></tr></thead><tbody><tr><td colspan="10" align="left" valign="top" rowspan="1"><bold>For all FTD</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Left insula</td><td align="right" valign="top" rowspan="1" colspan="1">44</td><td align="center" valign="top" rowspan="1" colspan="1">4</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">1198</td><td align="left" valign="top" rowspan="1" colspan="1">0.001</td><td align="left" valign="top" rowspan="1" colspan="1">0.016</td><td align="left" valign="top" rowspan="1" colspan="1">3.17%</td><td align="left" valign="top" rowspan="1" colspan="1">4.10</td><td align="center" valign="top" rowspan="1" colspan="1">1.69–5.35</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Right insula</td><td align="right" valign="top" rowspan="1" colspan="1">−44</td><td align="center" valign="top" rowspan="1" colspan="1">6</td><td align="center" valign="top" rowspan="1" colspan="1">0</td><td align="left" valign="top" rowspan="1" colspan="1">455</td><td align="left" valign="top" rowspan="1" colspan="1">0.001</td><td align="left" valign="top" rowspan="1" colspan="1">0.015</td><td align="left" valign="top" rowspan="1" colspan="1">3.37%</td><td align="left" valign="top" rowspan="1" colspan="1">4.87</td><td align="center" valign="top" rowspan="1" colspan="1">2.08–5.31</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Left OFC</td><td align="right" valign="top" rowspan="1" colspan="1">24</td><td align="center" valign="top" rowspan="1" colspan="1">54</td><td align="center" valign="top" rowspan="1" colspan="1">−36</td><td align="left" valign="top" rowspan="1" colspan="1">194</td><td align="left" valign="top" rowspan="1" colspan="1">0.007</td><td align="left" valign="top" rowspan="1" colspan="1">0.045</td><td align="left" valign="top" rowspan="1" colspan="1">4.54%</td><td align="left" valign="top" rowspan="1" colspan="1">4.79</td><td align="center" valign="top" rowspan="1" colspan="1">2.76–7.19</td></tr><tr><td colspan="10" align="left" valign="top" rowspan="1"><bold>Behavioral variant FTD (n = 7)</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Left thalamus</td><td align="right" valign="top" rowspan="1" colspan="1">22</td><td align="center" valign="top" rowspan="1" colspan="1">−6</td><td align="center" valign="top" rowspan="1" colspan="1">−8</td><td align="left" valign="top" rowspan="1" colspan="1">140</td><td align="left" valign="top" rowspan="1" colspan="1">0.018</td><td align="left" valign="top" rowspan="1" colspan="1">0.10</td><td align="left" valign="top" rowspan="1" colspan="1">5.22%</td><td align="left" valign="top" rowspan="1" colspan="1">2.29</td><td align="center" valign="top" rowspan="1" colspan="1">−0.43–13.04</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Left anterior cingulate</td><td align="right" valign="top" rowspan="1" colspan="1">12</td><td align="center" valign="top" rowspan="1" colspan="1">36</td><td align="center" valign="top" rowspan="1" colspan="1">24</td><td align="left" valign="top" rowspan="1" colspan="1">438</td><td align="left" valign="top" rowspan="1" colspan="1">0.004</td><td align="left" valign="top" rowspan="1" colspan="1">0.048</td><td align="left" valign="top" rowspan="1" colspan="1">5.93%</td><td align="left" valign="top" rowspan="1" colspan="1">3.28</td><td align="center" valign="top" rowspan="1" colspan="1">1.16–7.93</td></tr><tr><td colspan="10" align="left" valign="top" rowspan="1"><bold>Semantic dementia (n = 8)</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Right insula</td><td align="right" valign="top" rowspan="1" colspan="1">−36</td><td align="center" valign="top" rowspan="1" colspan="1">22</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">109</td><td align="left" valign="top" rowspan="1" colspan="1">0.006</td><td align="left" valign="top" rowspan="1" colspan="1">0.086</td><td align="left" valign="top" rowspan="1" colspan="1">4.77%</td><td align="left" valign="top" rowspan="1" colspan="1">3.32</td><td align="center" valign="top" rowspan="1" colspan="1">1.55–9.26</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Left OFC</td><td align="right" valign="top" rowspan="1" colspan="1">38</td><td align="center" valign="top" rowspan="1" colspan="1">44</td><td align="center" valign="top" rowspan="1" colspan="1">0</td><td align="left" valign="top" rowspan="1" colspan="1">272</td><td align="left" valign="top" rowspan="1" colspan="1">0.004</td><td align="left" valign="top" rowspan="1" colspan="1">0.056</td><td align="left" valign="top" rowspan="1" colspan="1">5.34%</td><td align="left" valign="top" rowspan="1" colspan="1">3.42</td><td align="center" valign="top" rowspan="1" colspan="1">1.7–9.33</td></tr></tbody></table><table-wrap-foot><fn id="tfn2-ndt-7-415"><p><bold>Abbreviations:</bold> CI, confidence interval; FTD, frontotemporal dementia syndromes; OFC, orbitofrontal cortex.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t3-ndt-7-415" position="float"><label>Table 3</label><caption><p>Repeated measures <italic>t</italic>-test results for 16 study completers on secondary behavioral and functional outcome measures</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1">Behavioral or functional Outcome measure (minimum– maximum score possible)</th><th align="left" valign="top" rowspan="1" colspan="1">Baseline mean, SD</th><th align="left" valign="top" rowspan="1" colspan="1">Two months mean, SD</th><th align="left" valign="top" rowspan="1" colspan="1">Change from baseline</th><th align="left" valign="top" rowspan="1" colspan="1"><italic>P</italic> value [95% CI] for repeated-measures <italic>t</italic>-test</th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Frontal Assessment Battery (0–18)</td><td align="center" valign="top" rowspan="1" colspan="1">9.82, 5.09</td><td align="center" valign="top" rowspan="1" colspan="1">9.58, 5.75</td><td align="left" valign="top" rowspan="1" colspan="1">−2.4%<xref ref-type="table-fn" rid="tfn3-ndt-7-415">a</xref></td><td align="left" valign="top" rowspan="1" colspan="1">0.69 [−1.0–1.5]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Frontal Behavioral Inventory (0–72)</td><td align="center" valign="top" rowspan="1" colspan="1">27, 12.38</td><td align="center" valign="top" rowspan="1" colspan="1">26.35, 11.61</td><td align="left" valign="top" rowspan="1" colspan="1">−2.4%</td><td align="left" valign="top" rowspan="1" colspan="1">0.33 [−0.9–2.0]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Stereotypy Rating Inventory (0–60)</td><td align="center" valign="top" rowspan="1" colspan="1">11.76, 471</td><td align="center" valign="top" rowspan="1" colspan="1">10.52, 9.41</td><td align="left" valign="top" rowspan="1" colspan="1">−10.5%</td><td align="left" valign="top" rowspan="1" colspan="1">0.22 [−0.9–3.5]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Clinical Dementia Rating scale (0–3)</td><td align="center" valign="top" rowspan="1" colspan="1">1.35, 0.90</td><td align="center" valign="top" rowspan="1" colspan="1">1.44, 0.81</td><td align="left" valign="top" rowspan="1" colspan="1">+6.7%</td><td align="left" valign="top" rowspan="1" colspan="1">0.42 [−0.3–0.2]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Sum of boxes CDR (0–15)</td><td align="center" valign="top" rowspan="1" colspan="1">6.97, 4.6</td><td align="center" valign="top" rowspan="1" colspan="1">7.26, 4.35</td><td align="left" valign="top" rowspan="1" colspan="1">+4.2%</td><td align="left" valign="top" rowspan="1" colspan="1">0.29 [−0.9–0.4]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Sum of boxes CDR-FTD (n = 9, 0–24)</td><td align="center" valign="top" rowspan="1" colspan="1">7.17, 3.82</td><td align="center" valign="top" rowspan="1" colspan="1">6.94, 3.75</td><td align="left" valign="top" rowspan="1" colspan="1">−3.2%</td><td align="left" valign="top" rowspan="1" colspan="1">0.60 [−0.7–1.2]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">UDPRS (motor subscale) (0–64)</td><td align="center" valign="top" rowspan="1" colspan="1">4.18, 6.03</td><td align="center" valign="top" rowspan="1" colspan="1">3.71, 6.31</td><td align="left" valign="top" rowspan="1" colspan="1">−11.2%</td><td align="left" valign="top" rowspan="1" colspan="1">0.47 [−1.1–1.6]</td></tr></tbody></table><table-wrap-foot><fn id="tfn3-ndt-7-415"><label>a</label><p><bold>Note:</bold> Lower scores indicate reduction in severity for all instruments except the Frontal Assessment Battery, for which higher scores indicate reduction in symptom severity.</p></fn><fn id="tfn4-ndt-7-415"><p><bold>Abbreviations:</bold> UDPRS, United Parkinson Disease Rating Scale; CDR, Clinical Dementia Rating; CI, confidence interval.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Chow, Tiffany W" sort="Chow, Tiffany W" uniqKey="Chow T" first="Tiffany W" last="Chow">Tiffany W. Chow</name></region><name sortKey="Binns, Malcolm A" sort="Binns, Malcolm A" uniqKey="Binns M" first="Malcolm A" last="Binns">Malcolm A. Binns</name><name sortKey="Black, Sandra E" sort="Black, Sandra E" uniqKey="Black S" first="Sandra E" last="Black">Sandra E. Black</name><name sortKey="Black, Sandra E" sort="Black, Sandra E" uniqKey="Black S" first="Sandra E" last="Black">Sandra E. Black</name><name sortKey="Chow, Tiffany W" sort="Chow, Tiffany W" uniqKey="Chow T" first="Tiffany W" last="Chow">Tiffany W. Chow</name><name sortKey="Freedman, Morris" sort="Freedman, Morris" uniqKey="Freedman M" first="Morris" last="Freedman">Morris Freedman</name><name sortKey="Graff Guerrero, Ariel" sort="Graff Guerrero, Ariel" uniqKey="Graff Guerrero A" first="Ariel" last="Graff-Guerrero">Ariel Graff-Guerrero</name><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><name sortKey="Masellis, Mario" sort="Masellis, Mario" uniqKey="Masellis M" first="Mario" last="Masellis">Mario Masellis</name><name sortKey="Masellis, Mario" sort="Masellis, Mario" uniqKey="Masellis M" first="Mario" last="Masellis">Mario Masellis</name><name sortKey="Pollock, Bruce G" sort="Pollock, Bruce G" uniqKey="Pollock B" first="Bruce G" last="Pollock">Bruce G. Pollock</name><name sortKey="Tang Wai, David F" sort="Tang Wai, David F" uniqKey="Tang Wai D" first="David F" last="Tang-Wai">David F. Tang-Wai</name><name sortKey="Verhoeff, Nicolaas Plg" sort="Verhoeff, Nicolaas Plg" uniqKey="Verhoeff N" first="Nicolaas Plg" last="Verhoeff">Nicolaas Plg Verhoeff</name><name sortKey="Wilson, Alan A" sort="Wilson, Alan A" uniqKey="Wilson A" first="Alan A" last="Wilson">Alan A. Wilson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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