Locus coeruleus neuron density and parkinsonism in older adults without Parkinson's disease.
Identifieur interne : 000D53 ( PubMed/Checkpoint ); précédent : 000D52; suivant : 000D54Locus coeruleus neuron density and parkinsonism in older adults without Parkinson's disease.
Auteurs : Aron S. Buchman [États-Unis] ; Sukriti Nag ; Joshua M. Shulman ; Andrew S P. Lim ; Veronique G J M. Vanderhorst ; Sue E. Leurgans ; Julie A. Schneider ; David A. BennettSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2012.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Amyloid.
- pathology : Aging, Lewy Bodies, Locus Coeruleus, Neurons, Parkinsonian Disorders.
- ultrastructure : Neurons.
- Aged, Aged, 80 and over, Cell Count, Female, Humans, Male, Postmortem Changes, Psychiatric Status Rating Scales.
Abstract
Previous work has showed that nigral neuron density is related to the severity of parkinsonism proximate to death in older persons without a clinical diagnosis of Parkinson's disease (PD). We tested the hypothesis that neuron density in other brain stem aminergic nuclei is also related to the severity of parkinsonism. We studied brain autopsies from 125 deceased older adults without PD enrolled in the Memory and Aging Project, a clinicopathologic investigation. Parkinsonism was assessed with a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS). We measured neuron density in the substantia nigra, ventral tegmental area, locus coeruleus, and dorsal raphe, along with postmortem indices of Lewy body disease, Alzheimer's disease and cerebrovascular pathologies. Mean age at death was 88.0 years, and global parkinsonism was 14.8 (SD, 9.50). In a series of regression models that controlled for demographics and neuron density in the substantia nigra, neuron density in the locus coeruleus (estimate, -0.261; SE, 0.117; P = .028) but not in the ventral tegmental area or dorsal raphe was associated with severity of global parkinsonism proximate to death. These findings were unchanged in models that controlled for postmortem interval, whole-brain weight, and other common neuropathologies including Alzheimer's disease and Lewy body pathology and cerebrovascular vascular pathologies. In older adults without a clinical diagnosis of PD, neuron density in locus coeruleus nuclei is associated with the severity of parkinsonism and may contribute to late-life motor impairments.
DOI: 10.1002/mds.25142
PubMed: 23038629
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Locus coeruleus neuron density and parkinsonism in older adults without Parkinson's disease.</title><author><name sortKey="Buchman, Aron S" sort="Buchman, Aron S" uniqKey="Buchman A" first="Aron S" last="Buchman">Aron S. Buchman</name><affiliation wicri:level="1"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA. Aron_S_Buchman@rush.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612</wicri:regionArea><wicri:noRegion>Illinois 60612</wicri:noRegion></affiliation></author><author><name sortKey="Nag, Sukriti" sort="Nag, Sukriti" uniqKey="Nag S" first="Sukriti" last="Nag">Sukriti Nag</name></author><author><name sortKey="Shulman, Joshua M" sort="Shulman, Joshua M" uniqKey="Shulman J" first="Joshua M" last="Shulman">Joshua M. Shulman</name></author><author><name sortKey="Lim, Andrew S P" sort="Lim, Andrew S P" uniqKey="Lim A" first="Andrew S P" last="Lim">Andrew S P. Lim</name></author><author><name sortKey="Vanderhorst, Veronique G J M" sort="Vanderhorst, Veronique G J M" uniqKey="Vanderhorst V" first="Veronique G J M" last="Vanderhorst">Veronique G J M. Vanderhorst</name></author><author><name sortKey="Leurgans, Sue E" sort="Leurgans, Sue E" uniqKey="Leurgans S" first="Sue E" last="Leurgans">Sue E. Leurgans</name></author><author><name sortKey="Schneider, Julie A" sort="Schneider, Julie A" uniqKey="Schneider J" first="Julie A" last="Schneider">Julie A. Schneider</name></author><author><name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A" last="Bennett">David A. Bennett</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="doi">10.1002/mds.25142</idno><idno type="RBID">pubmed:23038629</idno><idno type="pmid">23038629</idno><idno type="wicri:Area/PubMed/Corpus">000C12</idno><idno type="wicri:Area/PubMed/Curation">000C12</idno><idno type="wicri:Area/PubMed/Checkpoint">000D53</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Locus coeruleus neuron density and parkinsonism in older adults without Parkinson's disease.</title><author><name sortKey="Buchman, Aron S" sort="Buchman, Aron S" uniqKey="Buchman A" first="Aron S" last="Buchman">Aron S. Buchman</name><affiliation wicri:level="1"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA. Aron_S_Buchman@rush.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612</wicri:regionArea><wicri:noRegion>Illinois 60612</wicri:noRegion></affiliation></author><author><name sortKey="Nag, Sukriti" sort="Nag, Sukriti" uniqKey="Nag S" first="Sukriti" last="Nag">Sukriti Nag</name></author><author><name sortKey="Shulman, Joshua M" sort="Shulman, Joshua M" uniqKey="Shulman J" first="Joshua M" last="Shulman">Joshua M. Shulman</name></author><author><name sortKey="Lim, Andrew S P" sort="Lim, Andrew S P" uniqKey="Lim A" first="Andrew S P" last="Lim">Andrew S P. Lim</name></author><author><name sortKey="Vanderhorst, Veronique G J M" sort="Vanderhorst, Veronique G J M" uniqKey="Vanderhorst V" first="Veronique G J M" last="Vanderhorst">Veronique G J M. Vanderhorst</name></author><author><name sortKey="Leurgans, Sue E" sort="Leurgans, Sue E" uniqKey="Leurgans S" first="Sue E" last="Leurgans">Sue E. Leurgans</name></author><author><name sortKey="Schneider, Julie A" sort="Schneider, Julie A" uniqKey="Schneider J" first="Julie A" last="Schneider">Julie A. Schneider</name></author><author><name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A" last="Bennett">David A. Bennett</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Aging (pathology)</term><term>Amyloid (metabolism)</term><term>Cell Count</term><term>Female</term><term>Humans</term><term>Lewy Bodies (pathology)</term><term>Locus Coeruleus (pathology)</term><term>Male</term><term>Neurons (pathology)</term><term>Neurons (ultrastructure)</term><term>Parkinsonian Disorders (pathology)</term><term>Postmortem Changes</term><term>Psychiatric Status Rating Scales</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amyloid</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Aging</term><term>Lewy Bodies</term><term>Locus Coeruleus</term><term>Neurons</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Cell Count</term><term>Female</term><term>Humans</term><term>Male</term><term>Postmortem Changes</term><term>Psychiatric Status Rating Scales</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Previous work has showed that nigral neuron density is related to the severity of parkinsonism proximate to death in older persons without a clinical diagnosis of Parkinson's disease (PD). We tested the hypothesis that neuron density in other brain stem aminergic nuclei is also related to the severity of parkinsonism. We studied brain autopsies from 125 deceased older adults without PD enrolled in the Memory and Aging Project, a clinicopathologic investigation. Parkinsonism was assessed with a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS). We measured neuron density in the substantia nigra, ventral tegmental area, locus coeruleus, and dorsal raphe, along with postmortem indices of Lewy body disease, Alzheimer's disease and cerebrovascular pathologies. Mean age at death was 88.0 years, and global parkinsonism was 14.8 (SD, 9.50). In a series of regression models that controlled for demographics and neuron density in the substantia nigra, neuron density in the locus coeruleus (estimate, -0.261; SE, 0.117; P = .028) but not in the ventral tegmental area or dorsal raphe was associated with severity of global parkinsonism proximate to death. These findings were unchanged in models that controlled for postmortem interval, whole-brain weight, and other common neuropathologies including Alzheimer's disease and Lewy body pathology and cerebrovascular vascular pathologies. In older adults without a clinical diagnosis of PD, neuron density in locus coeruleus nuclei is associated with the severity of parkinsonism and may contribute to late-life motor impairments.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">23038629</PMID><DateCreated><Year>2012</Year><Month>11</Month><Day>29</Day></DateCreated><DateCompleted><Year>2013</Year><Month>05</Month><Day>13</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>27</Volume><Issue>13</Issue><PubDate><Year>2012</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Locus coeruleus neuron density and parkinsonism in older adults without Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>1625-31</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.25142</ELocationID><Abstract><AbstractText>Previous work has showed that nigral neuron density is related to the severity of parkinsonism proximate to death in older persons without a clinical diagnosis of Parkinson's disease (PD). We tested the hypothesis that neuron density in other brain stem aminergic nuclei is also related to the severity of parkinsonism. We studied brain autopsies from 125 deceased older adults without PD enrolled in the Memory and Aging Project, a clinicopathologic investigation. Parkinsonism was assessed with a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS). We measured neuron density in the substantia nigra, ventral tegmental area, locus coeruleus, and dorsal raphe, along with postmortem indices of Lewy body disease, Alzheimer's disease and cerebrovascular pathologies. Mean age at death was 88.0 years, and global parkinsonism was 14.8 (SD, 9.50). In a series of regression models that controlled for demographics and neuron density in the substantia nigra, neuron density in the locus coeruleus (estimate, -0.261; SE, 0.117; P = .028) but not in the ventral tegmental area or dorsal raphe was associated with severity of global parkinsonism proximate to death. These findings were unchanged in models that controlled for postmortem interval, whole-brain weight, and other common neuropathologies including Alzheimer's disease and Lewy body pathology and cerebrovascular vascular pathologies. In older adults without a clinical diagnosis of PD, neuron density in locus coeruleus nuclei is associated with the severity of parkinsonism and may contribute to late-life motor impairments.</AbstractText><CopyrightInformation>Copyright © 2012 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Buchman</LastName><ForeName>Aron S</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA. Aron_S_Buchman@rush.edu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nag</LastName><ForeName>Sukriti</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Shulman</LastName><ForeName>Joshua M</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Lim</LastName><ForeName>Andrew S P</ForeName><Initials>AS</Initials></Author><Author ValidYN="Y"><LastName>VanderHorst</LastName><ForeName>Veronique G J M</ForeName><Initials>VG</Initials></Author><Author ValidYN="Y"><LastName>Leurgans</LastName><ForeName>Sue E</ForeName><Initials>SE</Initials></Author><Author ValidYN="Y"><LastName>Schneider</LastName><ForeName>Julie A</ForeName><Initials>JA</Initials></Author><Author ValidYN="Y"><LastName>Bennett</LastName><ForeName>David A</ForeName><Initials>DA</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K08 AG034290</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K08AG034290</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AG017917</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AG024480</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS078009</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS079623</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01AG17917</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01AG24480</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01NS079623</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>10</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000682">Amyloid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Neurobiol Aging. 2003 Mar-Apr;24(2):197-211</RefSource><PMID Version="1">12498954</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Curr Alzheimer Res. 2012 Jul;9(6):646-63</RefSource><PMID Version="1">22471867</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Neurol. 2004 Oct;56(4):532-9</RefSource><PMID Version="1">15389895</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brain. 1991 Oct;114 ( Pt 5):2283-301</RefSource><PMID Version="1">1933245</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Gerontol A Biol Sci Med Sci. 1999 Apr;54(4):M191-6</RefSource><PMID Version="1">10219010</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Arch Neurol. 2006 Apr;63(4):584-8</RefSource><PMID Version="1">16606773</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Neurol. 2006 May;5(5):406-12</RefSource><PMID Version="1">16632311</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Biochem Pharmacol. 2007 Jul 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Neurol. 2003 Mar;60(3):337-41</RefSource><PMID Version="1">12633144</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000369">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000375">Aging</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000473">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000682">Amyloid</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000378">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002452">Cell Count</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016631">Lewy Bodies</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008125">Locus Coeruleus</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000473">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009474">Neurons</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000473">pathology</QualifierName><QualifierName MajorTopicYN="N" UI="Q000648">ultrastructure</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D020734">Parkinsonian Disorders</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000473">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011180">Postmortem Changes</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011569">Psychiatric Status Rating Scales</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">NIHMS450817</OtherID><OtherID Source="NLM">PMC3628555</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>6</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2012</Year><Month>7</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2012</Year><Month>7</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="aheadofprint"><Year>2012</Year><Month>10</Month><Day>4</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>10</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>10</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>5</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.25142</ArticleId><ArticleId IdType="pubmed">23038629</ArticleId><ArticleId IdType="pmc">PMC3628555</ArticleId><ArticleId IdType="mid">NIHMS450817</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A" last="Bennett">David A. Bennett</name><name sortKey="Leurgans, Sue E" sort="Leurgans, Sue E" uniqKey="Leurgans S" first="Sue E" last="Leurgans">Sue E. Leurgans</name><name sortKey="Lim, Andrew S P" sort="Lim, Andrew S P" uniqKey="Lim A" first="Andrew S P" last="Lim">Andrew S P. Lim</name><name sortKey="Nag, Sukriti" sort="Nag, Sukriti" uniqKey="Nag S" first="Sukriti" last="Nag">Sukriti Nag</name><name sortKey="Schneider, Julie A" sort="Schneider, Julie A" uniqKey="Schneider J" first="Julie A" last="Schneider">Julie A. Schneider</name><name sortKey="Shulman, Joshua M" sort="Shulman, Joshua M" uniqKey="Shulman J" first="Joshua M" last="Shulman">Joshua M. Shulman</name><name sortKey="Vanderhorst, Veronique G J M" sort="Vanderhorst, Veronique G J M" uniqKey="Vanderhorst V" first="Veronique G J M" last="Vanderhorst">Veronique G J M. Vanderhorst</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Buchman, Aron S" sort="Buchman, Aron S" uniqKey="Buchman A" first="Aron S" last="Buchman">Aron S. 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