Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study.
Identifieur interne : 002685 ( Ncbi/Merge ); précédent : 002684; suivant : 002686Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study.
Auteurs : Maria C. Rodriguez-Oroz [Espagne] ; Pablo Martínez Lage ; Jose Sanchez-Mut ; Isabel Lamet ; Javier Pagonabarraga ; Jon B. Toledo ; David García-Garcia ; Pedro Clavero ; Lluis Samaranch ; Cecilia Irurzun ; Juan M. Matsubara ; Jaione Irigoien ; Emilia Bescos ; Jaime Kulisevsky ; Jordi Pérez-Tur ; Jose A. ObesoSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2009.
English descriptors
- KwdEn :
- 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase (genetics), Aged, Aged, 80 and over, Brain (pathology), Carbon-Nitrogen Ligases (genetics), Case-Control Studies, Cognition Disorders (blood), Cognition Disorders (etiology), Cognition Disorders (genetics), Cognition Disorders (pathology), Cystathionine beta-Synthase (genetics), Depression (etiology), Female, Folic Acid (blood), Homocysteine (blood), Humans, Immunoassay (methods), Logistic Models, Magnetic Resonance Imaging (methods), Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Parkinson Disease (blood), Parkinson Disease (complications), Parkinson Disease (genetics), Parkinson Disease (pathology), Polymorphism, Genetic, Severity of Illness Index, Vitamin B 12 (blood), Vitamin B 6 (blood).
- MESH :
- chemical , blood : Folic Acid, Homocysteine, Vitamin B 12, Vitamin B 6.
- chemical , genetics : 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase, Carbon-Nitrogen Ligases, Cystathionine beta-Synthase.
- blood : Cognition Disorders, Parkinson Disease.
- complications : Parkinson Disease.
- etiology : Cognition Disorders, Depression.
- genetics : Cognition Disorders, Parkinson Disease.
- methods : Immunoassay, Magnetic Resonance Imaging.
- pathology : Brain, Cognition Disorders, Parkinson Disease.
- Aged, Aged, 80 and over, Case-Control Studies, Female, Humans, Logistic Models, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Polymorphism, Genetic, Severity of Illness Index.
Abstract
The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.
DOI: 10.1002/mds.22522
PubMed: 19452554
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Rodriguez-Oroz</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University Clinic and Medical School of Navarra, Pamplona, Spain. mcroroz@unav.es</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology, University Clinic and Medical School of Navarra, Pamplona</wicri:regionArea><wicri:noRegion>Pamplona</wicri:noRegion></affiliation></author><author><name sortKey="Lage, Pablo Martinez" sort="Lage, Pablo Martinez" uniqKey="Lage P" first="Pablo Martínez" last="Lage">Pablo Martínez Lage</name></author><author><name sortKey="Sanchez Mut, Jose" sort="Sanchez Mut, Jose" uniqKey="Sanchez Mut J" first="Jose" last="Sanchez-Mut">Jose Sanchez-Mut</name></author><author><name sortKey="Lamet, Isabel" sort="Lamet, Isabel" uniqKey="Lamet I" first="Isabel" last="Lamet">Isabel Lamet</name></author><author><name sortKey="Pagonabarraga, Javier" sort="Pagonabarraga, Javier" uniqKey="Pagonabarraga J" first="Javier" last="Pagonabarraga">Javier Pagonabarraga</name></author><author><name sortKey="Toledo, Jon B" sort="Toledo, Jon B" uniqKey="Toledo J" first="Jon B" last="Toledo">Jon B. 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Rodriguez-Oroz</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University Clinic and Medical School of Navarra, Pamplona, Spain. mcroroz@unav.es</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology, University Clinic and Medical School of Navarra, Pamplona</wicri:regionArea><wicri:noRegion>Pamplona</wicri:noRegion></affiliation></author><author><name sortKey="Lage, Pablo Martinez" sort="Lage, Pablo Martinez" uniqKey="Lage P" first="Pablo Martínez" last="Lage">Pablo Martínez Lage</name></author><author><name sortKey="Sanchez Mut, Jose" sort="Sanchez Mut, Jose" uniqKey="Sanchez Mut J" first="Jose" last="Sanchez-Mut">Jose Sanchez-Mut</name></author><author><name sortKey="Lamet, Isabel" sort="Lamet, Isabel" uniqKey="Lamet I" first="Isabel" last="Lamet">Isabel Lamet</name></author><author><name sortKey="Pagonabarraga, Javier" sort="Pagonabarraga, Javier" uniqKey="Pagonabarraga J" first="Javier" last="Pagonabarraga">Javier Pagonabarraga</name></author><author><name sortKey="Toledo, Jon B" sort="Toledo, Jon B" uniqKey="Toledo J" first="Jon B" last="Toledo">Jon B. Toledo</name></author><author><name sortKey="Garcia Garcia, David" sort="Garcia Garcia, David" uniqKey="Garcia Garcia D" first="David" last="García-Garcia">David García-Garcia</name></author><author><name sortKey="Clavero, Pedro" sort="Clavero, Pedro" uniqKey="Clavero P" first="Pedro" last="Clavero">Pedro Clavero</name></author><author><name sortKey="Samaranch, Lluis" sort="Samaranch, Lluis" uniqKey="Samaranch L" first="Lluis" last="Samaranch">Lluis Samaranch</name></author><author><name sortKey="Irurzun, Cecilia" sort="Irurzun, Cecilia" uniqKey="Irurzun C" first="Cecilia" last="Irurzun">Cecilia Irurzun</name></author><author><name sortKey="Matsubara, Juan M" sort="Matsubara, Juan M" uniqKey="Matsubara J" first="Juan M" last="Matsubara">Juan M. Matsubara</name></author><author><name sortKey="Irigoien, Jaione" sort="Irigoien, Jaione" uniqKey="Irigoien J" first="Jaione" last="Irigoien">Jaione Irigoien</name></author><author><name sortKey="Bescos, Emilia" sort="Bescos, Emilia" uniqKey="Bescos E" first="Emilia" last="Bescos">Emilia Bescos</name></author><author><name sortKey="Kulisevsky, Jaime" sort="Kulisevsky, Jaime" uniqKey="Kulisevsky J" first="Jaime" last="Kulisevsky">Jaime Kulisevsky</name></author><author><name sortKey="Perez Tur, Jordi" sort="Perez Tur, Jordi" uniqKey="Perez Tur J" first="Jordi" last="Pérez-Tur">Jordi Pérez-Tur</name></author><author><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="Jose A" last="Obeso">Jose A. Obeso</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="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase (genetics)</term><term>Aged</term><term>Aged, 80 and over</term><term>Brain (pathology)</term><term>Carbon-Nitrogen Ligases (genetics)</term><term>Case-Control Studies</term><term>Cognition Disorders (blood)</term><term>Cognition Disorders (etiology)</term><term>Cognition Disorders (genetics)</term><term>Cognition Disorders (pathology)</term><term>Cystathionine beta-Synthase (genetics)</term><term>Depression (etiology)</term><term>Female</term><term>Folic Acid (blood)</term><term>Homocysteine (blood)</term><term>Humans</term><term>Immunoassay (methods)</term><term>Logistic Models</term><term>Magnetic Resonance Imaging (methods)</term><term>Male</term><term>Mental Status Schedule</term><term>Middle Aged</term><term>Neuropsychological Tests</term><term>Parkinson Disease (blood)</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (pathology)</term><term>Polymorphism, Genetic</term><term>Severity of Illness Index</term><term>Vitamin B 12 (blood)</term><term>Vitamin B 6 (blood)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Folic Acid</term><term>Homocysteine</term><term>Vitamin B 12</term><term>Vitamin B 6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase</term><term>Carbon-Nitrogen Ligases</term><term>Cystathionine beta-Synthase</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Cognition Disorders</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Cognition Disorders</term><term>Depression</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cognition Disorders</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Immunoassay</term><term>Magnetic Resonance Imaging</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Cognition Disorders</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Case-Control Studies</term><term>Female</term><term>Humans</term><term>Logistic Models</term><term>Male</term><term>Mental Status Schedule</term><term>Middle Aged</term><term>Neuropsychological Tests</term><term>Polymorphism, Genetic</term><term>Severity of Illness Index</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">19452554</PMID><DateCreated><Year>2009</Year><Month>08</Month><Day>03</Day></DateCreated><DateCompleted><Year>2009</Year><Month>10</Month><Day>22</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>10</Issue><PubDate><Year>2009</Year><Month>Jul</Month><Day>30</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study.</ArticleTitle><Pagination><MedlinePgn>1437-44</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.22522</ELocationID><Abstract><AbstractText>The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.</AbstractText><CopyrightInformation>Copyright 2009 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rodriguez-Oroz</LastName><ForeName>Maria C</ForeName><Initials>MC</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Clinic and Medical School of Navarra, Pamplona, Spain. mcroroz@unav.es</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lage</LastName><ForeName>Pablo Martínez</ForeName><Initials>PM</Initials></Author><Author ValidYN="Y"><LastName>Sanchez-Mut</LastName><ForeName>Jose</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Lamet</LastName><ForeName>Isabel</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Pagonabarraga</LastName><ForeName>Javier</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Toledo</LastName><ForeName>Jon B</ForeName><Initials>JB</Initials></Author><Author ValidYN="Y"><LastName>García-Garcia</LastName><ForeName>David</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Clavero</LastName><ForeName>Pedro</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Samaranch</LastName><ForeName>Lluis</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Irurzun</LastName><ForeName>Cecilia</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Matsubara</LastName><ForeName>Juan M</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Irigoien</LastName><ForeName>Jaione</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Bescos</LastName><ForeName>Emilia</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Kulisevsky</LastName><ForeName>Jaime</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Pérez-Tur</LastName><ForeName>Jordi</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Obeso</LastName><ForeName>Jose A</ForeName><Initials>JA</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0LVT1QZ0BA</RegistryNumber><NameOfSubstance UI="D006710">Homocysteine</NameOfSubstance></Chemical><Chemical><RegistryNumber>8059-24-3</RegistryNumber><NameOfSubstance UI="D025101">Vitamin B 6</NameOfSubstance></Chemical><Chemical><RegistryNumber>935E97BOY8</RegistryNumber><NameOfSubstance UI="D005492">Folic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.1.1.13</RegistryNumber><NameOfSubstance UI="D013766">5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 4.2.1.22</RegistryNumber><NameOfSubstance UI="D003541">Cystathionine beta-Synthase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.3.-</RegistryNumber><NameOfSubstance UI="D019731">Carbon-Nitrogen Ligases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.3.3.2</RegistryNumber><NameOfSubstance UI="C021557">5,10-methenyltetrahydrofolate synthetase</NameOfSubstance></Chemical><Chemical><RegistryNumber>P6YC3EG204</RegistryNumber><NameOfSubstance UI="D014805">Vitamin B 12</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013766">5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><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="D001921">Brain</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D019731">Carbon-Nitrogen Ligases</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016022">Case-Control Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D003072">Cognition Disorders</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000097">blood</QualifierName><QualifierName MajorTopicYN="N" UI="Q000209">etiology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000473">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D003541">Cystathionine beta-Synthase</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D003863">Depression</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000209">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005492">Folic Acid</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006710">Homocysteine</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000097">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007118">Immunoassay</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000379">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016015">Logistic Models</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008279">Magnetic Resonance Imaging</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000379">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008609">Mental Status Schedule</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008875">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009483">Neuropsychological Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000097">blood</QualifierName><QualifierName MajorTopicYN="N" UI="Q000150">complications</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000473">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011110">Polymorphism, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D012720">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D014805">Vitamin B 12</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D025101">Vitamin B 6</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>5</Month><Day>20</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>5</Month><Day>20</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2009</Year><Month>10</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.22522</ArticleId><ArticleId IdType="pubmed">19452554</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Espagne</li></country></list><tree><noCountry><name sortKey="Bescos, Emilia" sort="Bescos, Emilia" uniqKey="Bescos E" first="Emilia" last="Bescos">Emilia Bescos</name><name sortKey="Clavero, Pedro" sort="Clavero, Pedro" uniqKey="Clavero P" first="Pedro" last="Clavero">Pedro Clavero</name><name sortKey="Garcia Garcia, David" sort="Garcia Garcia, David" uniqKey="Garcia Garcia D" first="David" last="García-Garcia">David García-Garcia</name><name sortKey="Irigoien, Jaione" sort="Irigoien, Jaione" uniqKey="Irigoien J" first="Jaione" last="Irigoien">Jaione Irigoien</name><name sortKey="Irurzun, Cecilia" sort="Irurzun, Cecilia" uniqKey="Irurzun C" first="Cecilia" last="Irurzun">Cecilia Irurzun</name><name sortKey="Kulisevsky, Jaime" sort="Kulisevsky, Jaime" uniqKey="Kulisevsky J" first="Jaime" last="Kulisevsky">Jaime Kulisevsky</name><name sortKey="Lage, Pablo Martinez" sort="Lage, Pablo Martinez" uniqKey="Lage P" first="Pablo Martínez" last="Lage">Pablo Martínez Lage</name><name sortKey="Lamet, Isabel" sort="Lamet, Isabel" uniqKey="Lamet I" first="Isabel" last="Lamet">Isabel Lamet</name><name sortKey="Matsubara, Juan M" sort="Matsubara, Juan M" uniqKey="Matsubara J" first="Juan M" last="Matsubara">Juan M. Matsubara</name><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="Jose A" last="Obeso">Jose A. Obeso</name><name sortKey="Pagonabarraga, Javier" sort="Pagonabarraga, Javier" uniqKey="Pagonabarraga J" first="Javier" last="Pagonabarraga">Javier Pagonabarraga</name><name sortKey="Perez Tur, Jordi" sort="Perez Tur, Jordi" uniqKey="Perez Tur J" first="Jordi" last="Pérez-Tur">Jordi Pérez-Tur</name><name sortKey="Samaranch, Lluis" sort="Samaranch, Lluis" uniqKey="Samaranch L" first="Lluis" last="Samaranch">Lluis Samaranch</name><name sortKey="Sanchez Mut, Jose" sort="Sanchez Mut, Jose" uniqKey="Sanchez Mut J" first="Jose" last="Sanchez-Mut">Jose Sanchez-Mut</name><name sortKey="Toledo, Jon B" sort="Toledo, Jon B" uniqKey="Toledo J" first="Jon B" last="Toledo">Jon B. Toledo</name></noCountry><country name="Espagne"><noRegion><name sortKey="Rodriguez Oroz, Maria C" sort="Rodriguez Oroz, Maria C" uniqKey="Rodriguez Oroz M" first="Maria C" last="Rodriguez-Oroz">Maria C. 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