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Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis

Identifieur interne : 004E82 ( Main/Exploration ); précédent : 004E81; suivant : 004E83

Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis

Auteurs : Davis C. Ryman [États-Unis] ; Natalia Acosta-Baena [Colombie] ; Paul S. Aisen [États-Unis] ; Thomas Bird [États-Unis] ; Adrian Danek [Allemagne] ; Nick C. Fox [Royaume-Uni] ; Alison Goate [États-Unis] ; Peter Frommelt ; Bernardino Ghetti ; Jessica B. S. Langbaum [Maurice (pays)] ; Francisco Lopera [Colombie] ; Ralph Martins [Australie] ; Colin L. Masters [Australie] ; Richard P. Mayeux [États-Unis] ; Eric Mcdade [États-Unis] ; Sonia Moreno [Colombie] ; Eric M. Reiman [Maurice (pays)] ; John M. Ringman [États-Unis] ; Steve Salloway [États-Unis] ; Peter R. Schofield [Australie] ; Reisa Sperling [États-Unis] ; Pierre N. Tariot [Maurice (pays)] ; CHENGJIE XIONG [États-Unis] ; John C. Morris [États-Unis] ; Randall J. Bateman [États-Unis]

Source :

Neurology [ 0028-3878 ] ; 2014.

RBID : Pascal:14-0196285

Descripteurs français

Pascal (Inist)
- Démence d'Alzheimer, Pathologie du système nerveux.

English descriptors

KwdEn :
- Alzheimer disease, Nervous system diseases.

Abstract

Objective: To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD. Methods: We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E28OA) and Volga German (PSEN2 N141l) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study. Results: We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10^-16, r² > 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex. Conclusions: Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.

Affiliations:

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Le document en format XML

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<author><name sortKey="Mcdade, Eric" sort="Mcdade, Eric" uniqKey="Mcdade E" first="Eric" last="Mcdade">Eric Mcdade</name>
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<author><name sortKey="Moreno, Sonia" sort="Moreno, Sonia" uniqKey="Moreno S" first="Sonia" last="Moreno">Sonia Moreno</name>
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<author><name sortKey="Reiman, Eric M" sort="Reiman, Eric M" uniqKey="Reiman E" first="Eric M." last="Reiman">Eric M. Reiman</name>
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<author><name sortKey="Schofield, Peter R" sort="Schofield, Peter R" uniqKey="Schofield P" first="Peter R." last="Schofield">Peter R. Schofield</name>
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<author><name sortKey="Tariot, Pierre N" sort="Tariot, Pierre N" uniqKey="Tariot P" first="Pierre N." last="Tariot">Pierre N. Tariot</name>
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<author><name sortKey="Chengjie Xiong" sort="Chengjie Xiong" uniqKey="Chengjie Xiong" last="Chengjie Xiong">CHENGJIE XIONG</name>
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<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Neurology, Washington University School of Medicine</s1>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis</title>
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<author><name sortKey="Acosta Baena, Natalia" sort="Acosta Baena, Natalia" uniqKey="Acosta Baena N" first="Natalia" last="Acosta-Baena">Natalia Acosta-Baena</name>
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<author><name sortKey="Danek, Adrian" sort="Danek, Adrian" uniqKey="Danek A" first="Adrian" last="Danek">Adrian Danek</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Neurologische Klinik Ludwig-Maximilians-Universirät Munich and German Center for Neurodegenerative Diseases</s1>
<s2>Munich</s2>
<s3>DEU</s3>
<sZ>5 aut.</sZ>
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<placeName><region type="land" nuts="1">Bavière</region>
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<s3>GBR</s3>
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<country>Royaume-Uni</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
<orgName type="university">University College de Londres</orgName>
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<author><name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Psychiatry, Washington University School of Medicine</s1>
<s2>St. Louis, MO</s2>
<s3>USA</s3>
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<country>États-Unis</country>
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<region type="state">Missouri (État)</region>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
<orgName type="institution">Université Washington de Saint-Louis</orgName>
</affiliation>
</author>
<author><name sortKey="Frommelt, Peter" sort="Frommelt, Peter" uniqKey="Frommelt P" first="Peter" last="Frommelt">Peter Frommelt</name>
</author>
<author><name sortKey="Ghetti, Bernardino" sort="Ghetti, Bernardino" uniqKey="Ghetti B" first="Bernardino" last="Ghetti">Bernardino Ghetti</name>
</author>
<author><name sortKey="Langbaum, Jessica B S" sort="Langbaum, Jessica B S" uniqKey="Langbaum J" first="Jessica B. S." last="Langbaum">Jessica B. S. Langbaum</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Banner Alzheimer's Institute</s1>
<s2>Phoenix, AZ</s2>
<s3>MUS</s3>
<sZ>10 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>Maurice (pays)</country>
<wicri:noRegion>Banner Alzheimer's Institute</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lopera, Francisco" sort="Lopera, Francisco" uniqKey="Lopera F" first="Francisco" last="Lopera">Francisco Lopera</name>
<affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Grupo de Neurociencias de Antioquia, Universidad de Antioquia</s1>
<s2>Medellín</s2>
<s3>COL</s3>
<sZ>2 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Colombie</country>
<wicri:noRegion>Medellín</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Martins, Ralph" sort="Martins, Ralph" uniqKey="Martins R" first="Ralph" last="Martins">Ralph Martins</name>
<affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Edith Cowan University</s1>
<s2>Western</s2>
<s3>AUS</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Edith Cowan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Masters, Colin L" sort="Masters, Colin L" uniqKey="Masters C" first="Colin L." last="Masters">Colin L. Masters</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Mental Health Research Institute, University of Melbourne</s1>
<s3>AUS</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Mental Health Research Institute, University of Melbourne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mayeux, Richard P" sort="Mayeux, Richard P" uniqKey="Mayeux R" first="Richard P." last="Mayeux">Richard P. Mayeux</name>
<affiliation wicri:level="4"><inist:fA14 i1="14"><s1>Department of Neurology, Columbia University</s1>
<s2>New York, NY</s2>
<s3>USA</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">New York</settlement>
<region type="state">État de New York</region>
</placeName>
<orgName type="university">Université Columbia</orgName>
</affiliation>
</author>
<author><name sortKey="Mcdade, Eric" sort="Mcdade, Eric" uniqKey="Mcdade E" first="Eric" last="Mcdade">Eric Mcdade</name>
<affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Department of Neurology, University of Pittsburgh</s1>
<s2>PA</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Moreno, Sonia" sort="Moreno, Sonia" uniqKey="Moreno S" first="Sonia" last="Moreno">Sonia Moreno</name>
<affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Grupo de Neurociencias de Antioquia, Universidad de Antioquia</s1>
<s2>Medellín</s2>
<s3>COL</s3>
<sZ>2 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Colombie</country>
<wicri:noRegion>Medellín</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Reiman, Eric M" sort="Reiman, Eric M" uniqKey="Reiman E" first="Eric M." last="Reiman">Eric M. Reiman</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Banner Alzheimer's Institute</s1>
<s2>Phoenix, AZ</s2>
<s3>MUS</s3>
<sZ>10 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>Maurice (pays)</country>
<wicri:noRegion>Banner Alzheimer's Institute</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ringman, John M" sort="Ringman, John M" uniqKey="Ringman J" first="John M." last="Ringman">John M. Ringman</name>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Easton Center for Alzheimer's Disease Research at UCLA</s1>
<s2>Los Angeles, CA</s2>
<s3>USA</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Easton Center for Alzheimer's Disease Research at UCLA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Salloway, Steve" sort="Salloway, Steve" uniqKey="Salloway S" first="Steve" last="Salloway">Steve Salloway</name>
<affiliation wicri:level="4"><inist:fA14 i1="16"><s1>Department of Neurology, Warren Alpert Medical School, Brown University</s1>
<s2>Providence, RI</s2>
<s3>USA</s3>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Providence (Rhode Island)</settlement>
<region type="state">Rhode Island</region>
</placeName>
<orgName type="university">Université Brown</orgName>
</affiliation>
</author>
<author><name sortKey="Schofield, Peter R" sort="Schofield, Peter R" uniqKey="Schofield P" first="Peter R." last="Schofield">Peter R. Schofield</name>
<affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Neuroscience Research Australia and University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sperling, Reisa" sort="Sperling, Reisa" uniqKey="Sperling R" first="Reisa" last="Sperling">Reisa Sperling</name>
<affiliation wicri:level="3"><inist:fA14 i1="17"><s1>Center for Alzheimer Research and Treatment, Brigham and Women's Hospital and Massachusetts General Hospital</s1>
<s2>Boston</s2>
<s3>USA</s3>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tariot, Pierre N" sort="Tariot, Pierre N" uniqKey="Tariot P" first="Pierre N." last="Tariot">Pierre N. Tariot</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Banner Alzheimer's Institute</s1>
<s2>Phoenix, AZ</s2>
<s3>MUS</s3>
<sZ>10 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>Maurice (pays)</country>
<wicri:noRegion>Banner Alzheimer's Institute</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chengjie Xiong" sort="Chengjie Xiong" uniqKey="Chengjie Xiong" last="Chengjie Xiong">CHENGJIE XIONG</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Biostatistics, Washington University School of Medicine</s1>
<s2>St. Louis, MO</s2>
<s3>USA</s3>
<sZ>23 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Saint-Louis (Missouri)</settlement>
<region type="state">Missouri (État)</region>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
<orgName type="institution">Université Washington de Saint-Louis</orgName>
</affiliation>
</author>
<author><name sortKey="Morris, John C" sort="Morris, John C" uniqKey="Morris J" first="John C." last="Morris">John C. Morris</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Neurology, Washington University School of Medicine</s1>
<s2>St. Louis, MO</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Saint-Louis (Missouri)</settlement>
<region type="state">Missouri (État)</region>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
<orgName type="institution">Université Washington de Saint-Louis</orgName>
</affiliation>
</author>
<author><name sortKey="Bateman, Randall J" sort="Bateman, Randall J" uniqKey="Bateman R" first="Randall J." last="Bateman">Randall J. Bateman</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Neurology, Washington University School of Medicine</s1>
<s2>St. Louis, MO</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Saint-Louis (Missouri)</settlement>
<region type="state">Missouri (État)</region>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
<orgName type="institution">Université Washington de Saint-Louis</orgName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Neurology</title>
<title level="j" type="abbreviated">Neurology</title>
<idno type="ISSN">0028-3878</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Neurology</title>
<title level="j" type="abbreviated">Neurology</title>
<idno type="ISSN">0028-3878</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alzheimer disease</term>
<term>Nervous system diseases</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Démence d'Alzheimer</term>
<term>Pathologie du   système nerveux</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Objective: To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD. Methods: We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E28OA) and Volga German (PSEN2 N141l) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study. Results: We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10<sup>-16</sup>
, r<sup>2</sup>
 > 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex. Conclusions: Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Colombie</li>
<li>Maurice (pays)</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Bavière</li>
<li>District de Haute-Bavière</li>
<li>Grand Londres</li>
<li>Massachusetts</li>
<li>Missouri (État)</li>
<li>Nouvelle-Galles du Sud</li>
<li>Pennsylvanie</li>
<li>Rhode Island</li>
<li>Washington (État)</li>
<li>État de New York</li>
</region>
<settlement><li>Boston</li>
<li>Londres</li>
<li>Munich</li>
<li>New York</li>
<li>Pittsburgh</li>
<li>Providence (Rhode Island)</li>
<li>Saint-Louis (Missouri)</li>
<li>Seattle</li>
<li>Sydney</li>
</settlement>
<orgName><li>University College de Londres</li>
<li>Université Brown</li>
<li>Université Columbia</li>
<li>Université Washington de Saint-Louis</li>
<li>Université de Pittsburgh</li>
<li>Université de Washington</li>
<li>École de médecine (Université Washington de Saint-Louis)</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Frommelt, Peter" sort="Frommelt, Peter" uniqKey="Frommelt P" first="Peter" last="Frommelt">Peter Frommelt</name>
<name sortKey="Ghetti, Bernardino" sort="Ghetti, Bernardino" uniqKey="Ghetti B" first="Bernardino" last="Ghetti">Bernardino Ghetti</name>
</noCountry>
<country name="États-Unis"><region name="Missouri (État)"><name sortKey="Ryman, Davis C" sort="Ryman, Davis C" uniqKey="Ryman D" first="Davis C." last="Ryman">Davis C. Ryman</name>
</region>
<name sortKey="Aisen, Paul S" sort="Aisen, Paul S" uniqKey="Aisen P" first="Paul S." last="Aisen">Paul S. Aisen</name>
<name sortKey="Bateman, Randall J" sort="Bateman, Randall J" uniqKey="Bateman R" first="Randall J." last="Bateman">Randall J. Bateman</name>
<name sortKey="Bird, Thomas" sort="Bird, Thomas" uniqKey="Bird T" first="Thomas" last="Bird">Thomas Bird</name>
<name sortKey="Chengjie Xiong" sort="Chengjie Xiong" uniqKey="Chengjie Xiong" last="Chengjie Xiong">CHENGJIE XIONG</name>
<name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<name sortKey="Mayeux, Richard P" sort="Mayeux, Richard P" uniqKey="Mayeux R" first="Richard P." last="Mayeux">Richard P. Mayeux</name>
<name sortKey="Mcdade, Eric" sort="Mcdade, Eric" uniqKey="Mcdade E" first="Eric" last="Mcdade">Eric Mcdade</name>
<name sortKey="Morris, John C" sort="Morris, John C" uniqKey="Morris J" first="John C." last="Morris">John C. Morris</name>
<name sortKey="Ringman, John M" sort="Ringman, John M" uniqKey="Ringman J" first="John M." last="Ringman">John M. Ringman</name>
<name sortKey="Salloway, Steve" sort="Salloway, Steve" uniqKey="Salloway S" first="Steve" last="Salloway">Steve Salloway</name>
<name sortKey="Sperling, Reisa" sort="Sperling, Reisa" uniqKey="Sperling R" first="Reisa" last="Sperling">Reisa Sperling</name>
</country>
<country name="Colombie"><noRegion><name sortKey="Acosta Baena, Natalia" sort="Acosta Baena, Natalia" uniqKey="Acosta Baena N" first="Natalia" last="Acosta-Baena">Natalia Acosta-Baena</name>
</noRegion>
<name sortKey="Lopera, Francisco" sort="Lopera, Francisco" uniqKey="Lopera F" first="Francisco" last="Lopera">Francisco Lopera</name>
<name sortKey="Moreno, Sonia" sort="Moreno, Sonia" uniqKey="Moreno S" first="Sonia" last="Moreno">Sonia Moreno</name>
</country>
<country name="Allemagne"><region name="Bavière"><name sortKey="Danek, Adrian" sort="Danek, Adrian" uniqKey="Danek A" first="Adrian" last="Danek">Adrian Danek</name>
</region>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C." last="Fox">Nick C. Fox</name>
</region>
</country>
<country name="Maurice (pays)"><noRegion><name sortKey="Langbaum, Jessica B S" sort="Langbaum, Jessica B S" uniqKey="Langbaum J" first="Jessica B. S." last="Langbaum">Jessica B. S. Langbaum</name>
</noRegion>
<name sortKey="Reiman, Eric M" sort="Reiman, Eric M" uniqKey="Reiman E" first="Eric M." last="Reiman">Eric M. Reiman</name>
<name sortKey="Tariot, Pierre N" sort="Tariot, Pierre N" uniqKey="Tariot P" first="Pierre N." last="Tariot">Pierre N. Tariot</name>
</country>
<country name="Australie"><noRegion><name sortKey="Martins, Ralph" sort="Martins, Ralph" uniqKey="Martins R" first="Ralph" last="Martins">Ralph Martins</name>
</noRegion>
<name sortKey="Masters, Colin L" sort="Masters, Colin L" uniqKey="Masters C" first="Colin L." last="Masters">Colin L. Masters</name>
<name sortKey="Schofield, Peter R" sort="Schofield, Peter R" uniqKey="Schofield P" first="Peter R." last="Schofield">Peter R. Schofield</name>
</country>
</tree>
</affiliations>
</record>

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Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis

Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis

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