Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder
Identifieur interne : 000271 ( Main/Corpus ); précédent : 000270; suivant : 000272Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder
Auteurs : Ronald B. Postuma ; Jean-François Gagnon ; Mélanie Vendette ; Catherine Desjardins ; Jacques Y. MontplaisirSource :
- Annals of Neurology [ 0364-5134 ] ; 2011-05.
Abstract
Objective:: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein‐mediated neurodegenerative disease—this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. Methods:: Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease‐free. Results:: Out of 64 patients, 62 (97%) participated in annual follow‐up. During follow‐up, 21 developed disease, and 41 remained disease‐free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease‐free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex‐adjusted normal vs 80.2 ± 26.3%; p = 0.003) and color vision (Farnsworth‐Munsell 100‐Hue color test [FM‐100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; p = 0.022). Kaplan‐Meier 5‐year‐disease‐free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (p = 0.029). Disease‐free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (p = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages. Interpretation:: Olfaction and color vision identify early‐stage synuclein‐mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages. Ann Neurol 2011;
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DOI: 10.1002/ana.22282
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Postuma</name><affiliation><mods:affiliation>Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Gagnon, Jean Rancois" sort="Gagnon, Jean Rancois" uniqKey="Gagnon J" first="Jean-François" last="Gagnon">Jean-François Gagnon</name><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Vendette, Melanie" sort="Vendette, Melanie" uniqKey="Vendette M" first="Mélanie" last="Vendette">Mélanie Vendette</name><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Desjardins, Catherine" sort="Desjardins, Catherine" uniqKey="Desjardins C" first="Catherine" last="Desjardins">Catherine Desjardins</name><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Montplaisir, Jacques Y" sort="Montplaisir, Jacques Y" uniqKey="Montplaisir J" first="Jacques Y." last="Montplaisir">Jacques Y. 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Postuma</name><affiliation><mods:affiliation>Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Gagnon, Jean Rancois" sort="Gagnon, Jean Rancois" uniqKey="Gagnon J" first="Jean-François" last="Gagnon">Jean-François Gagnon</name><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Vendette, Melanie" sort="Vendette, Melanie" uniqKey="Vendette M" first="Mélanie" last="Vendette">Mélanie Vendette</name><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Desjardins, Catherine" sort="Desjardins, Catherine" uniqKey="Desjardins C" first="Catherine" last="Desjardins">Catherine Desjardins</name><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Montplaisir, Jacques Y" sort="Montplaisir, Jacques Y" uniqKey="Montplaisir J" first="Jacques Y." last="Montplaisir">Jacques Y. Montplaisir</name><affiliation><mods:affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-05">2011-05</date><biblScope unit="volume">69</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="811">811</biblScope><biblScope unit="page" to="818">818</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">B4900BCBB2BBCB01C57569296C35331FD6F6E415</idno><idno type="DOI">10.1002/ana.22282</idno><idno type="ArticleID">ANA22282</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective:: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein‐mediated neurodegenerative disease—this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. Methods:: Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease‐free. Results:: Out of 64 patients, 62 (97%) participated in annual follow‐up. During follow‐up, 21 developed disease, and 41 remained disease‐free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease‐free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex‐adjusted normal vs 80.2 ± 26.3%; p = 0.003) and color vision (Farnsworth‐Munsell 100‐Hue color test [FM‐100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; p = 0.022). Kaplan‐Meier 5‐year‐disease‐free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (p = 0.029). Disease‐free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (p = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages. Interpretation:: Olfaction and color vision identify early‐stage synuclein‐mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages. Ann Neurol 2011;</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Ronald B. Postuma MD, MSc</name><affiliations><json:string>Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada</json:string><json:string>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</json:string></affiliations></json:item><json:item><name>Jean‐François Gagnon PhD</name><affiliations><json:string>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</json:string><json:string>Department of Psychiatry, Université de Montréal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>Mélanie Vendette BSc</name><affiliations><json:string>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</json:string></affiliations></json:item><json:item><name>Catherine Desjardins MSc</name><affiliations><json:string>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</json:string><json:string>Department of Psychiatry, Université de Montréal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>Jacques Y. Montplaisir MD, PhD</name><affiliations><json:string>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</json:string><json:string>Department of Psychiatry, Université de Montréal, Quebec, Canada</json:string></affiliations></json:item></author><articleId><json:string>ANA22282</json:string></articleId><language><json:string>eng</json:string></language><abstract>Objective:: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein‐mediated neurodegenerative disease—this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. Methods:: Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease‐free. Results:: Out of 64 patients, 62 (97%) participated in annual follow‐up. During follow‐up, 21 developed disease, and 41 remained disease‐free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease‐free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex‐adjusted normal vs 80.2 ± 26.3%; p = 0.003) and color vision (Farnsworth‐Munsell 100‐Hue color test [FM‐100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; p = 0.022). Kaplan‐Meier 5‐year‐disease‐free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (p = 0.029). Disease‐free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (p = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages. Interpretation:: Olfaction and color vision identify early‐stage synuclein‐mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages. 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Gouin Ouest, Montréal, Québec, Canada, H4J 1C5</p></note><affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</affiliation><affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-05"></date><biblScope unit="volume">69</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="811">811</biblScope><biblScope unit="page" to="818">818</biblScope></imprint></monogr><idno type="istex">B4900BCBB2BBCB01C57569296C35331FD6F6E415</idno><idno type="DOI">10.1002/ana.22282</idno><idno type="ArticleID">ANA22282</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objective:: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein‐mediated neurodegenerative disease—this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. Methods:: Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease‐free. Results:: Out of 64 patients, 62 (97%) participated in annual follow‐up. During follow‐up, 21 developed disease, and 41 remained disease‐free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease‐free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex‐adjusted normal vs 80.2 ± 26.3%; p = 0.003) and color vision (Farnsworth‐Munsell 100‐Hue color test [FM‐100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; p = 0.022). Kaplan‐Meier 5‐year‐disease‐free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (p = 0.029). Disease‐free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (p = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages. Interpretation:: Olfaction and color vision identify early‐stage synuclein‐mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages. 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Gouin Ouest, Montréal, Québec, Canada, H4J 1C5</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA22282.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="39"></count><count type="wordTotal" number="5218"></count></countGroup><titleGroup><title type="main" xml:lang="en">Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder</title><title type="short" xml:lang="en">Olfaction and Vision Identify Neurodegeneration</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Ronald B.</givenNames><familyName>Postuma</familyName><degrees>MD, MSc</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2 #af3"><personName><givenNames>Jean‐François</givenNames><familyName>Gagnon</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Mélanie</givenNames><familyName>Vendette</familyName><degrees>BSc</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2 #af3"><personName><givenNames>Catherine</givenNames><familyName>Desjardins</familyName><degrees>MSc</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af2 #af3" corresponding="yes"><personName><givenNames>Jacques Y.</givenNames><familyName>Montplaisir</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email>JY.Montplaisir@UMontreal.CA</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="CA" type="organization"><unparsedAffiliation>Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="CA" type="organization"><unparsedAffiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="CA" type="organization"><unparsedAffiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Objective:</title><p>For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein‐mediated neurodegenerative disease—this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease.</p></section><section xml:id="abs1-2"><title type="main">Methods:</title><p>Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease‐free.</p></section><section xml:id="abs1-3"><title type="main">Results:</title><p>Out of 64 patients, 62 (97%) participated in annual follow‐up. During follow‐up, 21 developed disease, and 41 remained disease‐free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease‐free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex‐adjusted normal vs 80.2 ± 26.3%; <i>p</i> = 0.003) and color vision (Farnsworth‐Munsell 100‐Hue color test [FM‐100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; <i>p</i> = 0.022). Kaplan‐Meier 5‐year‐disease‐free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (<i>p</i> = 0.029). Disease‐free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (<i>p</i> = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages.</p></section><section xml:id="abs1-4"><title type="main">Interpretation:</title><p>Olfaction and color vision identify early‐stage synuclein‐mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages. Ann Neurol 2011;</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Olfaction and Vision Identify Neurodegeneration</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder</title></titleInfo><name type="personal"><namePart type="given">Ronald B.</namePart><namePart type="family">Postuma</namePart><namePart type="termsOfAddress">MD, MSc</namePart><affiliation>Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada</affiliation><affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐François</namePart><namePart type="family">Gagnon</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</affiliation><affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mélanie</namePart><namePart type="family">Vendette</namePart><namePart type="termsOfAddress">BSc</namePart><affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Catherine</namePart><namePart type="family">Desjardins</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</affiliation><affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jacques Y.</namePart><namePart type="family">Montplaisir</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Coeur, Montréal, Québec, Canada</affiliation><affiliation>Department of Psychiatry, Université de Montréal, Quebec, Canada</affiliation><description>Correspondence: CRCPC, Centre d'étude du sommeil et des rythmes biologiques, Hôpital du Sacré‐Cœur de Montréal, 5400 Boul . Gouin Ouest, Montréal, Québec, Canada, H4J 1C5</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-05</dateIssued><dateCaptured encoding="w3cdtf">2010-06-28</dateCaptured><dateValid encoding="w3cdtf">2010-09-28</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">2</extent><extent unit="references">39</extent><extent unit="words">5218</extent></physicalDescription><abstract lang="en">Objective:: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein‐mediated neurodegenerative disease—this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. Methods:: Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease‐free. Results:: Out of 64 patients, 62 (97%) participated in annual follow‐up. During follow‐up, 21 developed disease, and 41 remained disease‐free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease‐free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex‐adjusted normal vs 80.2 ± 26.3%; p = 0.003) and color vision (Farnsworth‐Munsell 100‐Hue color test [FM‐100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; p = 0.022). Kaplan‐Meier 5‐year‐disease‐free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (p = 0.029). Disease‐free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (p = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages. Interpretation:: Olfaction and color vision identify early‐stage synuclein‐mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages. Ann Neurol 2011;</abstract><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>69</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>811</start><end>818</end><total>8</total></extent></part></relatedItem><identifier type="istex">B4900BCBB2BBCB01C57569296C35331FD6F6E415</identifier><identifier type="DOI">10.1002/ana.22282</identifier><identifier type="ArticleID">ANA22282</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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