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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Unrecognized preclinical Alzheimer disease confounds rs-fcMRI studies of normal aging</title>
<author><name sortKey="Brier, Matthew R" sort="Brier, Matthew R" uniqKey="Brier M" first="Matthew R." last="Brier">Matthew R. Brier</name>
</author>
<author><name sortKey="Thomas, Jewell B" sort="Thomas, Jewell B" uniqKey="Thomas J" first="Jewell B." last="Thomas">Jewell B. Thomas</name>
</author>
<author><name sortKey="Snyder, Abraham Z" sort="Snyder, Abraham Z" uniqKey="Snyder A" first="Abraham Z." last="Snyder">Abraham Z. Snyder</name>
</author>
<author><name sortKey="Wang, Liang" sort="Wang, Liang" uniqKey="Wang L" first="Liang" last="Wang">Liang Wang</name>
</author>
<author><name sortKey="Fagan, Anne M" sort="Fagan, Anne M" uniqKey="Fagan A" first="Anne M." last="Fagan">Anne M. Fagan</name>
</author>
<author><name sortKey="Benzinger, Tammie" sort="Benzinger, Tammie" uniqKey="Benzinger T" first="Tammie" last="Benzinger">Tammie Benzinger</name>
</author>
<author><name sortKey="Morris, John C" sort="Morris, John C" uniqKey="Morris J" first="John C." last="Morris">John C. Morris</name>
</author>
<author><name sortKey="Ances, Beau M" sort="Ances, Beau M" uniqKey="Ances B" first="Beau M." last="Ances">Beau M. Ances</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25261500</idno>
<idno type="pmc">4223085</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223085</idno>
<idno type="RBID">PMC:4223085</idno>
<idno type="doi">10.1212/WNL.0000000000000939</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000135</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000135</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Unrecognized preclinical Alzheimer disease confounds rs-fcMRI studies of normal aging</title>
<author><name sortKey="Brier, Matthew R" sort="Brier, Matthew R" uniqKey="Brier M" first="Matthew R." last="Brier">Matthew R. Brier</name>
</author>
<author><name sortKey="Thomas, Jewell B" sort="Thomas, Jewell B" uniqKey="Thomas J" first="Jewell B." last="Thomas">Jewell B. Thomas</name>
</author>
<author><name sortKey="Snyder, Abraham Z" sort="Snyder, Abraham Z" uniqKey="Snyder A" first="Abraham Z." last="Snyder">Abraham Z. Snyder</name>
</author>
<author><name sortKey="Wang, Liang" sort="Wang, Liang" uniqKey="Wang L" first="Liang" last="Wang">Liang Wang</name>
</author>
<author><name sortKey="Fagan, Anne M" sort="Fagan, Anne M" uniqKey="Fagan A" first="Anne M." last="Fagan">Anne M. Fagan</name>
</author>
<author><name sortKey="Benzinger, Tammie" sort="Benzinger, Tammie" uniqKey="Benzinger T" first="Tammie" last="Benzinger">Tammie Benzinger</name>
</author>
<author><name sortKey="Morris, John C" sort="Morris, John C" uniqKey="Morris J" first="John C." last="Morris">John C. Morris</name>
</author>
<author><name sortKey="Ances, Beau M" sort="Ances, Beau M" uniqKey="Ances B" first="Beau M." last="Ances">Beau M. Ances</name>
</author>
</analytic>
<series><title level="j">Neurology</title>
<idno type="ISSN">0028-3878</idno>
<idno type="eISSN">1526-632X</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Objective:</title>
<p>To determine whether, and to what degree, preclinical Alzheimer disease (AD) confounds studies of healthy aging where “healthy” is based on cognitive normality alone.</p>
</sec>
<sec><title>Methods:</title>
<p>We examined the effects of preclinical AD in cognitively normal older individuals using resting-state functional connectivity MRI. We investigated 2 groups of cognitively normal participants: one group with evidence of preclinical AD as assessed by CSF markers of AD and the other group with normal CSF biomarkers.</p>
</sec>
<sec><title>Results:</title>
<p>There were significant interactions between age and biomarker status in the default-mode, dorsal attention, and salience resting-state networks. In the group with evidence of preclinical AD, there were dramatic changes in functional connectivity with age. In the group without evidence of preclinical AD, those changes were greatly attenuated. In most regions with significant interactions of age and biomarker status, the age-related change in functional connectivity in the normal biomarker group was indistinguishable from zero.</p>
</sec>
<sec><title>Conclusions:</title>
<p>These results suggest that preclinical AD accounts for a substantial portion of the reported effects of aging in the extant functional connectivity literature.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Neurology</journal-id>
<journal-id journal-id-type="iso-abbrev">Neurology</journal-id>
<journal-id journal-id-type="hwp">neurology</journal-id>
<journal-id journal-id-type="publisher-id">neur</journal-id>
<journal-id journal-id-type="pmc">neurology</journal-id>
<journal-id journal-id-type="publisher-id">NEUROLOGY</journal-id>
<journal-title-group><journal-title>Neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0028-3878</issn>
<issn pub-type="epub">1526-632X</issn>
<publisher><publisher-name>Lippincott Williams & Wilkins</publisher-name>
<publisher-loc>Hagerstown, MD</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25261500</article-id>
<article-id pub-id-type="pmc">4223085</article-id>
<article-id pub-id-type="publisher-id">NEUROLOGY2014576413</article-id>
<article-id pub-id-type="doi">10.1212/WNL.0000000000000939</article-id>
<article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>26</subject>
<subject>121</subject>
</subj-group>
<subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Unrecognized preclinical Alzheimer disease confounds rs-fcMRI studies of normal aging</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Brier</surname>
<given-names>Matthew R.</given-names>
</name>
<degrees>BS</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Thomas</surname>
<given-names>Jewell B.</given-names>
</name>
<degrees>BA</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Snyder</surname>
<given-names>Abraham Z.</given-names>
</name>
<degrees>MD, PhD</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>Journal of Computational Neuroscience, Action Editor, 2009-</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>P30NS048056 (Marcus) 04/01/04-11/30/14 NIH/NINDS NINDS CENTER CORE FOR BRAIN IMAGING U01AG032438 (Morris) 09/15/08-12/31/14 NIH/NIA Dominantly Inherited Alzheimer Network U54MH091657 (Van Essen) 09/15/10-08/31/15 NIH/NIMH Mapping the Human Connectome: Structure, Function, and Heritability R01 MH093510 (PI: Pruett)ï¿½04/17/12-01/31/17 NIH/NIMH fcMRI in Infants at High Risk for Autism R01MH096482 (Corbetta) 02/16/12-11/30/16 NIH/NIMH ELECTROPHYSIOLOGICAL STUDIES O HUMAN ATTENTION P01AG026276 (Morris, John C) 09/30/05-05/31/16 NIH Antecendent Biomarkers for AD: The Adult Children Study R01 NS058714-04A1(Perlmutter) 07/01/12-06/30/17 NIH/NINDS Validation of Biomarkers for Nigrostriatal Neurons R01 NS077959 (Earhart)ï¿½09/30/12-07/31/17 NIH/NINDSï¿½ï¿½ Exercise and Parkinsonï¿½s:ï¿½Comparing Interventions and Exploring Neural Mechanisms R01 HD055741 (Piven, Pruett) 07/01/07-05/31/17 NICHD A Longitudinal MRI Study of Infants at Risk for Autism (fcMRI Image Processing Core) 1P01NS080675-01A1ï¿½(Raichle) 07/15/13-06/30/18 NIH/NINDSï¿½ï¿½ Glucose Metabolism and the Default Mode Network in Health and Disease R01 NS041509 (Perlmutter) 04/01/01- NIH Mechanisms of Deep Brain Stimulation R01 MH102471 (Snyder) 02/01/14-01/31/19 NIH-NIMH Functional Connectivity in the Brain: A New Approach</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Liang</given-names>
</name>
<degrees>MD</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Fagan</surname>
<given-names>Anne M.</given-names>
</name>
<degrees>PhD</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>Advisory Board: 1) Lilly 2) Roche 3) IBL International There are no conflicts of interest</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>1) 6,465,195 B2 10/15/2002 Predictive diagnostic for Alzheimers disease David Holtzman, Anne Fagan Niven, Steve Younkin, Linda Younkin 2) PCT/US09/050255 (7/10/2009, in process) A risk factor and new therapeutic target for Alzheimers disease Alison Goate, Carlos Cruchaga, David Holtzman, Anne Fagan Niven</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>1) Guidepoint Global (consultation on CSF biomarkers) 2) Wolters Kluwer (consultation on CSF biomarkers) 3) Coalition Against Major Diseases (CAMD) 4) AbbVie</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>NIH R01 AG043434 (PI: Roe) 9/30/12 ï¿½ 08/31/17 Driving Performance in Preclinical Alzheimerï¿½s Disease Dr. Fagan Niven is Co-Investigator on this grant. NIH/NIA P01 AG003991 (PI: Morris) 01/01/09-12/31/14 (NCE) Healthy Aging and Senile Dementia Dr. Fagan Niven is Co-Investigator for Project 2: ï¿½CSF Biomarkers of Antecedent ADï¿½ NIH/NIA U19 AG032438 (PI: Morris) 9/15/08 ï¿½ 6/30/14 Dominantly Inherited Alzheimer Network (DIAN): DIAN Biomarker Core Dr. Fagan Niven is the Leader of the Biomarker Core NIH/NIA R37 AG013956 (PI: Holtzman) 9/1/04-8/31/14 Effect of ApoE on CNS Neurons: Role of LRP Dr. Fagan Niven is co-investigator on this grant. Pilot Project (PIs: Fagan Niven, Bateman) 11/1/11-10/31/14 Hope Center for Neurological Disorders Quantitation of amyloid-β peptides in CSF of Alzheimerï¿½s disease participants by immunoprecipitation/mass spectrometry (IP/MS) and solid phase extraction/mass spectrometry (SPE/MS) Dr. Fagan Niven is Co-PI Investigator Initiated Research (PI: Bateman) Eli Lilly (1/1/2014 ï¿½ 12/31/14); Roche Pharmaceuticals (1/1/2014 ï¿½ 12/31/14); National Institutes of Health (9/20/13 ï¿½ 8/31/14) Dominantly Inherited Alzheimer Network (DIAN) Trial Dr. Fagan Niven is the Biomarker Core Leader of the DIAN Trial Investigator Initiated Research (PI: Bateman) DIAN Pharma Consortium (12/8/13 ï¿½ 12/8/14); Dominantly Inherited Alzheimer Network (DIAN) Trials Unit (TU) Dr. Fagan Niven is the Biomarker Working Group Leader of the DIAN-TU National Alzheimerï¿½s Coordinating Center (PI: Kukull) 07/01/13 ï¿½ 06/30/15 Validation of Non-Amyloid, non-Tau CSF Biomarkers of Alzheimerï¿½s Disease Dr. Fagan Niven is the PI of the subcontract</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Benzinger</surname>
<given-names>Tammie</given-names>
</name>
<degrees>MD, PhD</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>(1) Eli Lilly Advisory Board (2011)</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>(1) Compensation for development of CME materials for Quintiles</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>(1) Investigator initiated research grants, Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly). Support for the research projects only, no personal compensation or salary support.</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>(1) 5P01AG026276 (PI: J. Morris) 10/1/11-9/30/15 NIH/NIA Adult Children Study (ACS) Role: Project 4 Principal Investigator (T. Benzinger) (2) 1 U01AG032438 (PI: J. Morris) 9/30/08-6/30/14 NIH/NIA Dominantly Inherited Alzheimer Network (DIAN) Role: Core G (Imaging Core) Principal Investigator (T. Benzinger) (3) AG003991-27 (PI: J. Morris) 5/15/09ï¿½12/31/13 NIH/NIA HASD: Healthy Aging and Senile Dementia, Imaging Core (Core Director, T. Benzinger) (4) 1R01 NS066905-01 (PI: D. Marcus) 9/30/09 ï¿½ 6/30/2014 NIH/NINDS BIRN Resources Facilitate the Personalization of Malignant Brain Tumor Role: Co-Investigator (5) 1R01 AG043434 (PI: C. Roe) 9/30/12-8/31/17 NIH Title: Driving Performance in Preclinical Alzheimerï¿½s Disease Role: Co-investigator (6) 1P01NS059560-01A1 (PI: A. Cross) 10/1/2008 ï¿½ 7/31/12 NIH/NINDS Title: Biomarkers and Pathogenesis of MS: From Mouse to Human Role: Co-Investigator (7) Research Grant 6/01/10 ï¿½ 6/31/12 Washington University Institute of Clinical and Translational Science, UL1 RR024992 Title: qBOLD MR measurements of oxygen extraction fraction in patients with brain tumors Role: Project PI</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>(1) National Multiple Sclerosis Society, Research Grant.</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>(1) I have previously testified as a treating physician (not an expert witness).</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Morris</surname>
<given-names>John C.</given-names>
</name>
<degrees>MD</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>Lilly USA</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>Serves on the editorial advisory board of JAMA Neurology</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>1. Blackwell Publishing, 2009, for Burns J and Morris JC, “Mild Cognitive Impairment and Early Alzheimer's Disease”, copyright 2008 by John Wiley and Sons, Ltd 2. Taylor & Francis 2008; “Handbook of Dementing Illnesses, 2 Ed”, Morris JC, Galvin JE, Holtzman DM, Eds, copyright 2006</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>Receives research support from Eli Lilly/Avid Radiopharmaceuticals</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Ances</surname>
<given-names>Beau M.</given-names>
</name>
<degrees>MD, PhD</degrees>
<author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Gifts:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Editorial Boards:</title>
<list-item><p>Journal of Neurovirology</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Patents:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Publishing Royalties:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Employment, Commercial Entity:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Consultancies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Speakers' Bureaus:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Other Activities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Commercial Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Government Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Academic Entities:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Research Support, Foundations and Societies:</title>
<list-item><p>Alzheimer's Association</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
<p><list list-type="order"><title>Legal Proceedings:</title>
<list-item><p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<aff>From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.</aff>
</contrib-group>
<author-notes><corresp>Correspondence to Matthew R. Brier: <email>brierm@wusm.wustl.edu</email>
</corresp>
<fn fn-type="financial-disclosure"><p>Go to <ext-link ext-link-type="uri" xlink:href="http://neurology.org/">Neurology.org</ext-link>
 for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>28</day>
<month>10</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>28</day>
<month>10</month>
<year>2015</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the . </pmc-comment>
      <volume>83</volume>
<issue>18</issue>
<fpage>1613</fpage>
<lpage>1619</lpage>
<history><date date-type="received"><day>07</day>
<month>2</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>28</day>
<month>7</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© 2014 American Academy of Neurology</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>American Academy of Neurology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="NEUROLOGY2014576413.pdf"></self-uri>
<abstract><sec><title>Objective:</title>
<p>To determine whether, and to what degree, preclinical Alzheimer disease (AD) confounds studies of healthy aging where “healthy” is based on cognitive normality alone.</p>
</sec>
<sec><title>Methods:</title>
<p>We examined the effects of preclinical AD in cognitively normal older individuals using resting-state functional connectivity MRI. We investigated 2 groups of cognitively normal participants: one group with evidence of preclinical AD as assessed by CSF markers of AD and the other group with normal CSF biomarkers.</p>
</sec>
<sec><title>Results:</title>
<p>There were significant interactions between age and biomarker status in the default-mode, dorsal attention, and salience resting-state networks. In the group with evidence of preclinical AD, there were dramatic changes in functional connectivity with age. In the group without evidence of preclinical AD, those changes were greatly attenuated. In most regions with significant interactions of age and biomarker status, the age-related change in functional connectivity in the normal biomarker group was indistinguishable from zero.</p>
</sec>
<sec><title>Conclusions:</title>
<p>These results suggest that preclinical AD accounts for a substantial portion of the reported effects of aging in the extant functional connectivity literature.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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