CINXE.COM
Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study | Journal of Neurology, Neurosurgery & Psychiatry
<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE html> <html lang="en" dir="ltr" version="HTML+RDFa+MathML 1.1" xmlns:dc="http://purl.org/dc/terms/" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:og="http://ogp.me/ns#" xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#" xmlns:sioc="http://rdfs.org/sioc/ns#" xmlns:sioct="http://rdfs.org/sioc/types#" xmlns:skos="http://www.w3.org/2004/02/skos/core#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head profile="http://www.w3.org/1999/xhtml/vocab"> <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//securepubads.g.doubleclick.net" /> <link rel="dns-prefetch" href="//d1bxh8uas1mnw7.cloudfront.net" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <link rel="shortcut icon" href="https://jnnp.bmj.com/sites/default/themes/bmjj/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <script>window.dataLayer = window.dataLayer || [];window.dataLayer.push({"page":{"hwTitle":"A\u03b2 imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study","hwUrl":"https://jnnp.bmj.com/content/86/4/431","hwPath":"/content/86/4/431","hwType":"journal page"},"user":{"hwMemberID":"","hwLoggedIntoInstitutionID":"","hwLoggedIntoInstitution":"","hwAccessUsageTerms":"guest","hwRegisteredUser":"no","hwHasFullTextAccess":"no","hwEntitled":"no","mail":"e3b0c44298fc1c149afbf4c8996fb92427ae41e4649b934ca495991b7852b855"},"content":{"hwIssueDate":"2015-04-01","hwIssueDateTime":"2015-04-01 00:00:00","hwPublicationDate":"2018-04-11","hwPublicationDateTime":"2018-04-11 08:13:17","hwNlmArticleType":"research-article","hwDOI":"10.1136/jnnp-2014-308094","hwAuthors":"Kevin T Ong,Victor L Villemagne,Alex Bahar-Fuchs,Fiona Lamb,Narelle Langdon,Ana M Catafau,Andrew W Stephens,John Seibyl,Ludger M Dinkelborg,Cornelia B Reininger,Barbara Putz,Beate Rohde,Colin L Masters,Christopher C Rowe","hwContributors":"","hwIsEarlyRelease":"no","hwEissn":"1468-330X","hwPissn":"0022-3050","hwVolume":"86","hwIssue":"4","hwArticleType":"Neurodegeneration","hwTabView":"main_tab","hwViewType":"","hwAccessType":"Paywall","hwOpenAccess":"no","hwFreeAccess":"no","hwTaxonomy":"Dementia|Drugs: CNS (not psychiatric)|Memory disorders (psychiatry)|Psychiatry of old age|Brain stem / cerebellum|Radiology|Radiology (diagnostics)","hwCorpusCode":"jnnp","hwType":"article","hwSubtitle":null,"hwOverline":null,"hwPisaId":"jnnp;86/4/431","hwFirstPage":"431","hwLastPage":"436","hwIsLatestVersion":"yes","hwIsCurrentIssue":"no","hwIsOpenIssue":"no","hwHasFullText":"yes","hwHasPDF":"yes","hwParentTitle":"Journal of Neurology, Neurosurgery & Psychiatry: 86 (4)","hwElectronicPubDate":"2018-04-11","hwElectronicPubDateTime":"2018-04-11 08:13:17"}}); //--><!]]></script> <link rel="canonical" href="https://jnnp.bmj.com/content/86/4/431" /> <meta name="Generator" content="Drupal 7 (http://drupal.org)" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/86/4/431.full.pdf" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/86/4/431.full.txt" /> <meta name="issue_cover_image" content="https://jnnp.bmj.com/sites/default/files/highwire/jnnp/86/4.cover-source.jpg" /> <meta name="type" content="article" /> <meta name="category" content="research-article" /> <meta name="HW.identifier" content="/jnnp/86/4/431.atom" /> <meta name="HW.pisa" content="jnnp;86/4/431" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study" /> <meta name="DC.Identifier" content="10.1136/jnnp-2014-308094" /> <meta name="DC.Date" content="2015-04-01" /> <meta name="DC.Publisher" content="BMJ Publishing Group Ltd" /> <meta name="DC.Rights" content="Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions" /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="Background We assessed the clinical utility of β-amyloid (Aβ) imaging with 18F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time. Methods 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <−1.5. Results At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB−, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB− developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB− had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−. Conclusions 18F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline. Trial registration number NCT01138111." /> <meta name="DC.Contributor" content="Kevin T Ong" /> <meta name="DC.Contributor" content="Victor L Villemagne" /> <meta name="DC.Contributor" content="Alex Bahar-Fuchs" /> <meta name="DC.Contributor" content="Fiona Lamb" /> <meta name="DC.Contributor" content="Narelle Langdon" /> <meta name="DC.Contributor" content="Ana M Catafau" /> <meta name="DC.Contributor" content="Andrew W Stephens" /> <meta name="DC.Contributor" content="John Seibyl" /> <meta name="DC.Contributor" content="Ludger M Dinkelborg" /> <meta name="DC.Contributor" content="Cornelia B Reininger" /> <meta name="DC.Contributor" content="Barbara Putz" /> <meta name="DC.Contributor" content="Beate Rohde" /> <meta name="DC.Contributor" content="Colin L Masters" /> <meta name="DC.Contributor" content="Christopher C Rowe" /> <meta name="article:published_time" content="2015-04-01" /> <meta name="article:section" content="Neurodegeneration" /> <meta name="citation_title" content="Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study" /> <meta name="citation_abstract" lang="en" content="<h3>Background</h3> <p>We assessed the clinical utility of β-amyloid (Aβ) imaging with <sup>18</sup>F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer9s disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time.</p><h3>Methods</h3> <p>45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of &lt;−1.5.</p><h3>Results</h3> <p>At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB−, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB− developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB− had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−.</p><h3>Conclusions</h3> <p><sup>18</sup>F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline.</p><h3>Trial registration number</h3> <p>NCT01138111.</p>" /> <meta name="citation_journal_title" content="Journal of Neurology, Neurosurgery & Psychiatry" /> <meta name="citation_publisher" content="BMJ Publishing Group Ltd" /> <meta name="citation_publication_date" content="2015/04/01" /> <meta name="citation_mjid" content="jnnp;86/4/431" /> <meta name="citation_id" content="86/4/431" /> <meta name="citation_public_url" content="https://jnnp.bmj.com/content/86/4/431" /> <meta name="citation_abstract_html_url" content="https://jnnp.bmj.com/content/86/4/431.abstract" /> <meta name="citation_full_html_url" content="https://jnnp.bmj.com/content/86/4/431.full" /> <meta name="citation_pdf_url" content="https://jnnp.bmj.com/content/jnnp/86/4/431.full.pdf" /> <meta name="citation_issn" content="0022-3050" /> <meta name="citation_issn" content="1468-330X" /> <meta name="citation_journal_abbrev" content="J Neurol Neurosurg Psychiatry" /> <meta name="citation_doi" content="10.1136/jnnp-2014-308094" /> <meta name="citation_pmid" content="24970906" /> <meta name="citation_volume" content="86" /> <meta name="citation_issue" content="4" /> <meta name="citation_article_type" content="Research Article" /> <meta name="citation_section" content="Neurodegeneration" /> <meta name="citation_firstpage" content="431" /> <meta name="citation_lastpage" content="436" /> <meta name="citation_author" content="Kevin T Ong" /> <meta name="citation_author_institution" content="Centre for PET, Austin Health" /> <meta name="citation_author" content="Victor L Villemagne" /> <meta name="citation_author_institution" content="Centre for PET, Austin Health" /> <meta name="citation_author_institution" content="The Florey Institute of Neuroscience and Mental Health, The University of Melbourne" /> <meta name="citation_author" content="Alex Bahar-Fuchs" /> <meta name="citation_author_institution" content="Centre for PET, Austin Health" /> <meta name="citation_author_institution" content="Centre for Research on Aging, Health, and Wellbeing, The Australian National University" /> <meta name="citation_author" content="Fiona Lamb" /> <meta name="citation_author_institution" content="Centre for PET, Austin Health" /> <meta name="citation_author" content="Narelle Langdon" /> <meta name="citation_author_institution" content="Centre for PET, Austin Health" /> <meta name="citation_author" content="Ana M Catafau" /> <meta name="citation_author_institution" content="Piramal Imaging GmbH" /> <meta name="citation_author" content="Andrew W Stephens" /> <meta name="citation_author_institution" content="Piramal Imaging GmbH" /> <meta name="citation_author" content="John Seibyl" /> <meta name="citation_author_institution" content="Molecular NeuroImaging, L.L.C." /> <meta name="citation_author" content="Ludger M Dinkelborg" /> <meta name="citation_author_institution" content="Piramal Imaging GmbH" /> <meta name="citation_author" content="Cornelia B Reininger" /> <meta name="citation_author_institution" content="Bayer Healthcare" /> <meta name="citation_author" content="Barbara Putz" /> <meta name="citation_author_institution" content="Bayer Healthcare" /> <meta name="citation_author" content="Beate Rohde" /> <meta name="citation_author_institution" content="Bayer Healthcare" /> <meta name="citation_author" content="Colin L Masters" /> <meta name="citation_author_institution" content="The Florey Institute of Neuroscience and Mental Health, The University of Melbourne" /> <meta name="citation_author" content="Christopher C Rowe" /> <meta name="citation_author_institution" content="Centre for PET, Austin Health" /> <meta name="citation_reference" content="citation_journal_title=Annals of neurology;citation_journal_abbrev=Ann Neurol;citation_author=WE. Klunk;citation_author=H. Engler;citation_author=A. Nordberg;citation_title=Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.;citation_pages=306-319;citation_volume=55;citation_year=2004;citation_issue=3;citation_pmid=14991808;citation_doi=10.1002/ana.20009" /> <meta name="citation_reference" content="citation_journal_abbrev=Alzheimers Res Ther;citation_author=R. Laforce;citation_author=GD. Rabinovici;citation_title=Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications.;citation_pages=31-31;citation_volume=3;citation_year=2011;citation_issue=6;citation_pmid=22071129;citation_doi=10.1186/alzrt93" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=CC. Rowe;citation_author=S. Ng;citation_author=U. Ackermann;citation_title=Imaging beta-amyloid burden in aging and dementia;citation_pages=1718-25;citation_volume=68;citation_year=2007;citation_doi=10.1212/01.wnl.0000261919.22630.ea" /> <meta name="citation_reference" content="citation_journal_abbrev=Alzheimers Res Ther;citation_author=SM. Resnick;citation_author=J. Sojkova;citation_title=Amyloid imaging and memory change for prediction of cognitive impairment.;citation_pages=3-3;citation_volume=3;citation_year=2011;citation_issue=1;citation_pmid=21345176;citation_doi=10.1186/alzrt62" /> <meta name="citation_reference" content="citation_journal_abbrev=Alzheimers Dement;citation_author=MS. Albert;citation_author=ST. Dekosky;citation_author=D. Dickson;citation_title=The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.;citation_pages=270-279;citation_volume=7;citation_year=2011;citation_issue=3;citation_pmid=21514249;citation_doi=10.1016/j.jalz.2011.03.008" /> <meta name="citation_reference" content="citation_journal_title=Lancet. Neurology;citation_journal_abbrev=Lancet Neurol;citation_author=B. Dubois;citation_author=HH. Feldman;citation_author=C. Jacova;citation_title=Revising the definition of Alzheimer's disease: a new lexicon.;citation_pages=1118-1127;citation_volume=9;citation_year=2010;citation_issue=11;citation_pmid=20934914;citation_doi=10.1016/S1474-4422(10)70223-4" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=PM. Doraiswamy;citation_author=RA. Sperling;citation_author=RE. Coleman;citation_title=Amyloid-beta assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study;citation_pages=1636-44;citation_volume=79;citation_year=2012;citation_doi=10.1212/WNL.0b013e3182661f74" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=JC. Morris;citation_title=The Clinical Dementia Rating (CDR): current version and scoring rules;citation_pages=2412-14;citation_volume=43;citation_year=1993;citation_pmid=8232972;citation_doi=10.1212/WNL.43.11.2412-a" /> <meta name="citation_reference" content="citation_journal_title=Ann Neurol;citation_author=CC. Rowe;citation_author=P. Bourgeat;citation_author=KA. Ellis;citation_title=Predicting Alzheimer disease with beta-amyloid imaging: results from the Australian imaging, biomarkers, and lifestyle study of ageing;citation_pages=905-13;citation_volume=74;citation_year=2013;citation_pmid=24448836;citation_doi=10.1002/ana.24040" /> <meta name="citation_reference" content="citation_journal_title=Journal of medicinal chemistry;citation_journal_abbrev=J Med Chem;citation_author=W. Zhang;citation_author=S. Oya;citation_author=MP. Kung;citation_title=F-18 stilbenes as PET imaging agents for detecting beta-amyloid plaques in the brain.;citation_pages=5980-5988;citation_volume=48;citation_year=2005;citation_issue=19;citation_pmid=16162001;citation_doi=10.1021/jm050166g" /> <meta name="citation_reference" content="citation_journal_title=Lancet. Neurology;citation_journal_abbrev=Lancet Neurol;citation_author=CC. Rowe;citation_author=U. Ackerman;citation_author=W. Browne;citation_title=Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism.;citation_pages=129-135;citation_volume=7;citation_year=2008;citation_issue=2;citation_pmid=18191617;citation_doi=10.1016/S1474-4422(08)70001-2" /> <meta name="citation_reference" content="citation_journal_title=Lancet. Neurology;citation_journal_abbrev=Lancet Neurol;citation_author=H. Barthel;citation_author=HJ. Gertz;citation_author=S. Dresel;citation_title=Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study.;citation_pages=424-435;citation_volume=10;citation_year=2011;citation_issue=5;citation_pmid=21481640;citation_doi=10.1016/S1474-4422(11)70077-1" /> <meta name="citation_reference" content="citation_journal_title=J Nucl Med;citation_author=VL. Villemagne;citation_author=K. Ong;citation_author=RS. Mulligan;citation_title=Amyloid imaging with 18F-florbetaben in Alzheimer disease and other dementias;citation_volume=52;citation_year=2011;citation_pmid=21764791;citation_doi=10.2967/jnumed.111.089730" /> <meta name="citation_reference" content="citation_journal_title=European journal of nuclear medicine and molecular imaging;citation_journal_abbrev=Eur J Nucl Med Mol Imaging;citation_author=VL. Villemagne;citation_author=RS. Mulligan;citation_author=S. Pejoska;citation_title=Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer's disease.;citation_pages=983-989;citation_volume=39;citation_year=2012;citation_issue=6;citation_pmid=22398958;citation_doi=10.1007/s00259-012-2088-x" /> <meta name="citation_reference" content="citation_journal_title=Alzheimer Demen;citation_author=M. Sabbagh;citation_author=J. Seibyl;citation_author=H. Akatsu;citation_title=Multicentre phase 3 trial on florbetaben for beta-amyloid brain PET in Alzheimer's disease;citation_pages=90P;citation_volume=8;citation_year=2012;citation_issue=(4 Suppl)" /> <meta name="citation_reference" content="citation_journal_title=Archives of Neurology;citation_journal_abbrev=Arch Neurol;citation_author=GA. Jicha;citation_author=JE. Parisi;citation_author=DW. Dickson;citation_title=Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia.;citation_pages=674-681;citation_volume=63;citation_year=2006;citation_issue=5;citation_issn=0003-9942;citation_pmid=16682537;citation_doi=10.1001/archneur.63.5.674" /> <meta name="citation_reference" content="citation_journal_title=Alzheimer Demen;citation_author=K. Ong;citation_author=VL. Villemagne;citation_author=N. Lamngon;citation_title=Assessment of Aβ deposition in mild cognitive impairment with 18F-florbetaben;citation_pages=S26;citation_volume=6;citation_year=2010" /> <meta name="citation_reference" content="citation_journal_title=Brain;citation_author=EC. Mormino;citation_author=JT. Kluth;citation_author=CM. Madison;citation_title=Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects;citation_volume=132;citation_year=2009;citation_issue=(Pt 5);citation_pmid=19042931;citation_doi=10.1093/brain/awn320" /> <meta name="citation_reference" content="citation_journal_title=Lancet Neurol;citation_author=VL. Villemagne;citation_author=S. Burnham;citation_author=P. Bourgeat;citation_title=Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study;citation_pages=357-67;citation_volume=12;citation_year=2013;citation_pmid=23477989;citation_doi=10.1016/S1474-4422(13)70044-9" /> <meta name="citation_reference" content="citation_journal_title=J Alzheimers Dis;citation_author=A. Bahar-Fuchs;citation_author=V. Villemagne;citation_author=K. Ong;citation_title=Prediction of amyloid-beta pathology in amnestic mild cognitive impairment with neuropsychological tests;citation_pages=451-62;citation_volume=33;citation_year=2013;citation_pmid=23011220" /> <meta name="citation_reference" content="citation_journal_title=Journal of internal medicine;citation_journal_abbrev=J Intern Med;citation_author=RC. Petersen;citation_title=Mild cognitive impairment as a diagnostic entity.;citation_pages=183-194;citation_volume=256;citation_year=2004;citation_issue=3;citation_pmid=15324362;citation_doi=10.1111/j.1365-2796.2004.01388.x" /> <meta name="citation_reference" content="citation_journal_title=Journal of internal medicine;citation_journal_abbrev=J Intern Med;citation_author=B. Winblad;citation_author=K. Palmer;citation_author=M. Kivipelto;citation_title=Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.;citation_pages=240-246;citation_volume=256;citation_year=2004;citation_issue=3;citation_pmid=15324367;citation_doi=10.1111/j.1365-2796.2004.01380.x" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=G. McKhann;citation_author=D. Drachman;citation_author=M. Folstein;citation_title=Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease;citation_pages=939-44;citation_volume=34;citation_year=1984;citation_pmid=6610841;citation_doi=10.1212/WNL.34.7.939" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=IG. McKeith;citation_author=D. Galasko;citation_author=K. Kosaka;citation_title=Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop;citation_pages=1113-24;citation_volume=47;citation_year=1996;citation_doi=10.1212/WNL.47.5.1113" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=D. Neary;citation_author=JS. Snowden;citation_author=L. Gustafson;citation_title=Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria;citation_pages=1546-54;citation_volume=51;citation_year=1998;citation_pmid=9855500;citation_doi=10.1212/WNL.51.6.1546" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=JJ. Hauw;citation_author=SE. Daniel;citation_author=D. Dickson;citation_title=Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy);citation_pages=2015-19;citation_volume=44;citation_year=1994;citation_doi=10.1212/WNL.44.11.2015" /> <meta name="citation_reference" content="citation_journal_title=International psychogeriatrics / IPA;citation_journal_abbrev=Int Psychogeriatr;citation_author=KA. Ellis;citation_author=AI. Bush;citation_author=D. Darby;citation_title=The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease.;citation_pages=672-687;citation_volume=21;citation_year=2009;citation_issue=4;citation_pmid=19470201;citation_doi=10.1017/S1041610209009405" /> <meta name="citation_reference" content="citation_journal_title=Int J Alzheimers Dis;citation_author=S. Guo;citation_author=D. Getsios;citation_author=L. Hernandez;citation_title=Florbetaben PET in the early diagnosis of Alzheimer's disease: a discrete event simulation to explore its potential value and key data gaps;citation_pages=548157;citation_volume=2012;citation_year=2012;citation_pmid=23326754" /> <meta name="citation_reference" content="citation_journal_title=European journal of nuclear medicine and molecular imaging;citation_journal_abbrev=Eur J Nucl Med Mol Imaging;citation_author=A. Nordberg;citation_author=SF. Carter;citation_author=J. Rinne;citation_title=A European multicentre PET study of fibrillar amyloid in Alzheimer's disease.;citation_pages=104-114;citation_volume=40;citation_year=2013;citation_issue=1;citation_pmid=22961445;citation_doi=10.1007/s00259-012-2237-2" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=A. Okello;citation_author=J. Koivunen;citation_author=P. Edison;citation_title=Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study;citation_pages=754-60;citation_volume=73;citation_year=2009;citation_pmid=19587325;citation_doi=10.1212/WNL.0b013e3181b23564" /> <meta name="citation_reference" content="citation_journal_title=Annals of neurology;citation_journal_abbrev=Ann Neurol;citation_author=DA. Wolk;citation_author=JC. Price;citation_author=JA. Saxton;citation_title=Amyloid imaging in mild cognitive impairment subtypes.;citation_pages=557-568;citation_volume=65;citation_year=2009;citation_issue=5;citation_pmid=19475670;citation_doi=10.1002/ana.21598" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=GB. Frisoni;citation_author=M. Bocchetta;citation_author=G. Chetelat;citation_title=Imaging markers for Alzheimer disease: which vs how;citation_pages=487-500;citation_volume=81;citation_year=2013;citation_doi=10.1212/WNL.0b013e31829d86e8" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=CR. Jack;citation_author=DW. Dickson;citation_author=JE. Parisi;citation_title=Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia;citation_pages=750-7;citation_volume=58;citation_year=2002;citation_pmid=11889239;citation_doi=10.1212/WNL.58.5.750" /> <meta name="citation_reference" content="citation_journal_title=Lancet. Neurology;citation_journal_abbrev=Lancet Neurol;citation_author=CR. Jack;citation_author=DS. Knopman;citation_author=WJ. Jagust;citation_title=Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade.;citation_pages=119-128;citation_volume=9;citation_year=2010;citation_issue=1;citation_pmid=20083042;citation_doi=10.1016/S1474-4422(09)70299-6" /> <meta name="citation_reference" content="citation_journal_title=Neurology;citation_author=CR. Jack;citation_author=HJ. Wiste;citation_author=TG. Lesnick;citation_title=Brain beta-amyloid load approaches a plateau;citation_pages=890-6;citation_volume=80;citation_year=2013;citation_doi=10.1212/WNL.0b013e3182840bbe" /> <meta name="twitter:title" content="Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:image" content="https://jnnp.bmj.com/sites/default/files/highwire/jnnp/86/4.cover-source.jpg" /> <meta name="twitter:description" content="Background We assessed the clinical utility of β-amyloid (Aβ) imaging with 18F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time. Methods 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <−1.5. Results At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB−, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB− developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB− had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−. Conclusions 18F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline. Trial registration number NCT01138111." /> <meta name="og-title" property="og:title" content="Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study" /> <meta name="og-url" property="og:url" content="https://jnnp.bmj.com/content/86/4/431" /> <meta name="og-site-name" property="og:site_name" content="Journal of Neurology, Neurosurgery & Psychiatry" /> <meta name="og-description" property="og:description" content="Background We assessed the clinical utility of β-amyloid (Aβ) imaging with 18F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time. Methods 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <−1.5. Results At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB−, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB− developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB− had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−. Conclusions 18F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline. Trial registration number NCT01138111." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://jnnp.bmj.com/sites/default/files/highwire/jnnp/86/4.cover-source.jpg" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/86/4/431.ppt" /> <title>Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study | Journal of Neurology, Neurosurgery & Psychiatry</title> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__Uwlgxr2XCTH3JEn8X9M0Zmw2O61ONTKbcuCCFzbUoWc__GaVzYzSnTbY94ZNnLRDkzT_0FKDQBbP8csnKKJ9LSZA__qw1DJnk-5gO1smAYQ6Cv-FvON600W_QtaIfAGcQ9MYA.css" media="all" /> <!-- OneTrust Cookies Consent Notice start --> <script src="https://cookie-cdn.cookiepro.com/scripttemplates/otSDKStub.js" type="text/javascript" charset="UTF-8" data-domain-script="565e50dd-f6e9-46d6-91cd-5c40a270264f"></script> <script type="text/javascript"> function OnetrustAdsConsent(){ if(googletag.apiReady){ //console.log("GoogleTag API ready") googletag.pubads().disableInitialLoad(); if(OptanonActiveGroups.match(/,4,/)){ googletag.pubads().setRequestNonPersonalizedAds(0); //googletag.pubads().refresh(); } else{ googletag.pubads().setRequestNonPersonalizedAds(1); googletag.pubads().refresh(); } } else{ OnetrustAdsConsent(); } } function OptanonWrapper() { OnetrustAdsConsent(); } </script> <!-- OneTrust Cookies Consent Notice end --> <script type="text/javascript" src="/sites/default/files/advagg_js/js__DdxPgqGimsdUot2QWNz_pGsHzqNGpx6RMCWHpL8YWkg__c6zfK6oHHbLpTal5PdQxeQI3xGoCM8IXWtEHwIZr560__qw1DJnk-5gO1smAYQ6Cv-FvON600W_QtaIfAGcQ9MYA.js"></script> <script type="text/javascript" src="https://securepubads.g.doubleclick.net/tag/js/gpt.js"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__RplUf5n1SHvT_MHHQProZaAaHxo7a_9YZuaKWYnqVeQ__t8vznsHJmtJcTuSP5JnWJ92mdmFUGaXxtxwBatvNwmc__qw1DJnk-5gO1smAYQ6Cv-FvON600W_QtaIfAGcQ9MYA.js"></script> <script type="text/javascript" src="https://d1bxh8uas1mnw7.cloudfront.net/assets/embed.js"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__dNRQ0P3mzXReUF4250f2vTnR4K_GFl-M8oB_3K2j1fI__-eoy5F1B5hwy20bysxSQQrr2HBlAB7kgfK-OIh8VRRA__qw1DJnk-5gO1smAYQ6Cv-FvON600W_QtaIfAGcQ9MYA.js"></script> <script type="text/javascript" defer="defer" async="async" src="//cdn.foxycart.com/bmjpg.ecommerce.highwire.org/loader.js"></script> <script type="text/javascript" async="async" src="https://scholar.google.com/scholar_js/casa.js"></script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i<a.length;i++)j=a[i],e(j)?g(j,0,l,0):w(j)?B(j):Object(j)===j&&h(j,l);else Object(a)===a&&h(a,l)},B.addPrefix=function(a,b){z[a]=b},B.addFilter=function(a){x.push(a)},B.errorTimeout=1e4,null==b.readyState&&b.addEventListener&&(b.readyState="loading",b.addEventListener("DOMContentLoaded",A=function(){b.removeEventListener("DOMContentLoaded",A,0),b.readyState="complete"},0)),a.yepnope=k(),a.yepnope.executeStack=h,a.yepnope.injectJs=function(a,c,d,e,i,j){var k=b.createElement("script"),l,o,e=e||B.errorTimeout;k.src=a;for(o in d)k.setAttribute(o,d[o]);c=j?h:c||f,k.onreadystatechange=k.onload=function(){!l&&g(k.readyState)&&(l=1,c(),k.onload=k.onreadystatechange=null)},m(function(){l||(l=1,c(1))},e),i?k.onload():n.parentNode.insertBefore(k,n)},a.yepnope.injectCss=function(a,c,d,e,g,i){var e=b.createElement("link"),j,c=i?h:c||f;e.href=a,e.rel="stylesheet",e.type="text/css";for(j in d)e.setAttribute(j,d[j]);g||(n.parentNode.insertBefore(e,n),m(c,0))}})(this,document); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- yepnope({ test: Modernizr.matchmedia, nope: '/sites/all/libraries/media-match/media.match.min.js' }); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- var googletag = googletag || {}; googletag.cmd = googletag.cmd || []; googletag.slots = googletag.slots || {}; //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- var DC = { Date : "", subject : "" };var ga_article_category = "Neurodegeneration";var ga_article_page_type = "research-article";var ga_article_pub_year = "2014";var ga_customer_number = "";var ga_user_type = "";DC.Date = "2018-04-11";DC.subject = ""; //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- googletag.slots["mpu"] = googletag.defineSlot("/21798771943/JNNP-MPU", [[300, 250], [300, 600], [300, 300], [600, 500]], "dfp-ad-mpu") .addService(googletag.pubads()); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- googletag.slots["top"] = googletag.defineSlot("/21798771943/JNNP-TOP", [[970, 250], [900, 250], [728, 90], [468, 60], [320, 100], [320, 50]], "dfp-ad-top") .addService(googletag.pubads()); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- googletag.slots["bottom"] = googletag.defineSlot("/21798771943/JNNP-BOTTOM", [[970, 250], [900, 250], [728, 90], [468, 60], [320, 100], [320, 50]], "dfp-ad-bottom") .addService(googletag.pubads()); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- googletag.cmd.push(function() { googletag.pubads().enableAsyncRendering(); googletag.pubads().collapseEmptyDivs(); googletag.pubads().addEventListener("slotRenderEnded", function (event) { if (event.isEmpty) { var id = event.slot.getSlotElementId(); var x = document.getElementById(id); if (x.parentElement.classList.contains("dfp-tag-wrapper")) { x.parentElement.style.display = "none"; } } }); googletag.pubads().setTargeting("url", "/content/86/4/431"); googletag.pubads().setTargeting("page:hwTitle", "Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study"); googletag.pubads().setTargeting("page:hwUrl", "https://jnnp.bmj.com/content/86/4/431"); googletag.pubads().setTargeting("page:hwPath", "/content/86/4/431"); googletag.pubads().setTargeting("page:hwType", "journal page"); googletag.pubads().setTargeting("user:hwAccessUsageTerms", "guest"); googletag.pubads().setTargeting("user:hwRegisteredUser", "no"); googletag.pubads().setTargeting("user:hwHasFullTextAccess", "no"); googletag.pubads().setTargeting("user:hwEntitled", "no"); googletag.pubads().setTargeting("content:hwIssueDate", "2015-04-01"); googletag.pubads().setTargeting("content:hwIssueDateTime", "2015-04-01 00:00:00"); googletag.pubads().setTargeting("content:hwPublicationDate", "2018-04-11"); googletag.pubads().setTargeting("content:hwPublicationDateTime", "2018-04-11 08:13:17"); googletag.pubads().setTargeting("content:hwNlmArticleType", "research-article"); googletag.pubads().setTargeting("content:hwDOI", "10.1136/jnnp-2014-308094"); googletag.pubads().setTargeting("content:hwAuthors", ["Kevin T Ong","Victor L Villemagne","Alex Bahar-Fuchs","Fiona Lamb","Narelle Langdon","Ana M Catafau","Andrew W Stephens","John Seibyl","Ludger M Dinkelborg","Cornelia B Reininger","Barbara Putz","Beate Rohde","Colin L Masters","Christopher C Rowe"]); googletag.pubads().setTargeting("content:hwIsEarlyRelease", "no"); googletag.pubads().setTargeting("content:hwEissn", "1468-330X"); googletag.pubads().setTargeting("content:hwPissn", "0022-3050"); googletag.pubads().setTargeting("content:hwVolume", "86"); googletag.pubads().setTargeting("content:hwIssue", "4"); googletag.pubads().setTargeting("content:hwArticleType", "Neurodegeneration"); googletag.pubads().setTargeting("content:hwTabView", "main_tab"); googletag.pubads().setTargeting("content:hwAccessType", "Paywall"); googletag.pubads().setTargeting("content:hwOpenAccess", "no"); googletag.pubads().setTargeting("content:hwFreeAccess", "no"); googletag.pubads().setTargeting("content:hwTaxonomy", "Dementia|Drugs: CNS (not psychiatric)|Memory disorders (psychiatry)|Psychiatry of old age|Brain stem / cerebellum|Radiology|Radiology (diagnostics)"); googletag.pubads().setTargeting("content:hwCorpusCode", "jnnp"); googletag.pubads().setTargeting("content:hwType", "article"); googletag.pubads().setTargeting("content:hwPisaId", "jnnp;86/4/431"); googletag.pubads().setTargeting("content:hwFirstPage", "431"); googletag.pubads().setTargeting("content:hwLastPage", "436"); googletag.pubads().setTargeting("content:hwIsLatestVersion", "yes"); googletag.pubads().setTargeting("content:hwIsCurrentIssue", "no"); googletag.pubads().setTargeting("content:hwIsOpenIssue", "no"); googletag.pubads().setTargeting("content:hwHasFullText", "yes"); googletag.pubads().setTargeting("content:hwHasPDF", "yes"); googletag.pubads().setTargeting("content:hwParentTitle", ["Journal of Neurology","Neurosurgery & Psychiatry: 86 (4)"]); googletag.pubads().setTargeting("content:hwElectronicPubDate", "2018-04-11"); googletag.pubads().setTargeting("content:hwElectronicPubDateTime", "2018-04-11 08:13:17"); }); googletag.enableServices(); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- jQuery(document).ready(function() { var topOffset = jQuery(window).height() - jQuery('#article-top').offset().top + 100; jQuery('.article-go-to-top').css('margin-top', topOffset); jQuery('.article-go-to-top').affix({ offset: { top: function () { return (this.top = topOffset-10); }, bottom: function () { if(jQuery('#article-bottom-row').length){ return (this.bottom = jQuery('#footer').outerHeight(true) + jQuery('#article-bottom-row').outerHeight(true)+180) }else{ return (this.bottom = jQuery('#footer').outerHeight(true)+180) } } } }); }); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- if(typeof window.MathJax === "undefined") window.MathJax = { menuSettings: { zoom: "Click" } }; //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- jQuery.extend(Drupal.settings, {"basePath":"\/","pathPrefix":"","ajaxPageState":{"theme":"bmjj","theme_token":"0RBnfhJ26rDeK8fl5DTSmrj7It-SrRyz-_ImTixoh74"},"colorbox":{"opacity":"0.85","current":"{current} of {total}","previous":"\u00ab Prev","next":"Next \u00bb","close":"Close","maxWidth":"98%","maxHeight":"98%","fixed":true,"mobiledetect":true,"mobiledevicewidth":"480px"},"highwire":{"markup":[{"requested":"short-text","variant":"abstract","view":"abstract","pisa":"jnnp;86\/4\/431"},{"requested":"short-text","variant":"abstract","view":"abstract","pisa":"jnnp;86\/4\/431"},{"requested":"long","variant":"abstract","view":"abstract","pisa":"jnnp;86\/4\/431"},{"requested":"abstract","variant":"abstract","view":"abstract","pisa":"jnnp;86\/4\/431"},{"requested":"long","variant":"abstract","view":"abstract","pisa":"jnnp;86\/4\/431"},{"requested":"long","variant":"abstract","view":"abstract","pisa":"jnnp;86\/4\/431"}],"nid":"160406","apath":"\/jnnp\/86\/4\/431.atom","pisa":"jnnp;86\/4\/431","ac":{"\/jnnp\/86\/4\/431.atom":{"access":{"reprint":false,"full":false,"abstract":true},"pisa_id":"","apath":"\/jnnp\/86\/4\/431.atom","jcode":"jnnp"},"jnnp;86\/4\/431":{"access":{"full":false},"pisa_id":"jnnp;86\/4\/431","apath":"","jcode":"jnnp"}},"processed":["highwire_math"],"dataLayer":"{\u0022page\u0022:{\u0022hwTitle\u0022:\u0022A\\u03b2 imaging with 18F-florbetaben in prodromal Alzheimer\u0027s disease: a prospective outcome study\u0022,\u0022hwUrl\u0022:\u0022https:\\\/\\\/jnnp.bmj.com\\\/content\\\/86\\\/4\\\/431\u0022,\u0022hwPath\u0022:\u0022\\\/content\\\/86\\\/4\\\/431\u0022,\u0022hwType\u0022:\u0022journal page\u0022},\u0022user\u0022:{\u0022hwMemberID\u0022:\u0022\u0022,\u0022hwLoggedIntoInstitutionID\u0022:\u0022\u0022,\u0022hwLoggedIntoInstitution\u0022:\u0022\u0022,\u0022hwAccessUsageTerms\u0022:\u0022guest\u0022,\u0022hwRegisteredUser\u0022:\u0022no\u0022,\u0022hwHasFullTextAccess\u0022:\u0022no\u0022,\u0022hwEntitled\u0022:\u0022no\u0022,\u0022mail\u0022:\u0022e3b0c44298fc1c149afbf4c8996fb92427ae41e4649b934ca495991b7852b855\u0022},\u0022content\u0022:{\u0022hwIssueDate\u0022:\u00222015-04-01\u0022,\u0022hwIssueDateTime\u0022:\u00222015-04-01 00:00:00\u0022,\u0022hwPublicationDate\u0022:\u00222018-04-11\u0022,\u0022hwPublicationDateTime\u0022:\u00222018-04-11 08:13:17\u0022,\u0022hwNlmArticleType\u0022:\u0022research-article\u0022,\u0022hwDOI\u0022:\u002210.1136\\\/jnnp-2014-308094\u0022,\u0022hwAuthors\u0022:\u0022Kevin T Ong,Victor L Villemagne,Alex Bahar-Fuchs,Fiona Lamb,Narelle Langdon,Ana M Catafau,Andrew W Stephens,John Seibyl,Ludger M Dinkelborg,Cornelia B Reininger,Barbara Putz,Beate Rohde,Colin L Masters,Christopher C Rowe\u0022,\u0022hwContributors\u0022:\u0022\u0022,\u0022hwIsEarlyRelease\u0022:\u0022no\u0022,\u0022hwEissn\u0022:\u00221468-330X\u0022,\u0022hwPissn\u0022:\u00220022-3050\u0022,\u0022hwVolume\u0022:\u002286\u0022,\u0022hwIssue\u0022:\u00224\u0022,\u0022hwArticleType\u0022:\u0022Neurodegeneration\u0022,\u0022hwTabView\u0022:\u0022main_tab\u0022,\u0022hwViewType\u0022:\u0022\u0022,\u0022hwAccessType\u0022:\u0022Paywall\u0022,\u0022hwOpenAccess\u0022:\u0022no\u0022,\u0022hwFreeAccess\u0022:\u0022no\u0022,\u0022hwTaxonomy\u0022:\u0022Dementia|Drugs: CNS (not psychiatric)|Memory disorders (psychiatry)|Psychiatry of old age|Brain stem \\\/ cerebellum|Radiology|Radiology (diagnostics)\u0022,\u0022hwCorpusCode\u0022:\u0022jnnp\u0022,\u0022hwType\u0022:\u0022article\u0022,\u0022hwSubtitle\u0022:null,\u0022hwOverline\u0022:null,\u0022hwPisaId\u0022:\u0022jnnp;86\\\/4\\\/431\u0022,\u0022hwFirstPage\u0022:\u0022431\u0022,\u0022hwLastPage\u0022:\u0022436\u0022,\u0022hwIsLatestVersion\u0022:\u0022yes\u0022,\u0022hwIsCurrentIssue\u0022:\u0022no\u0022,\u0022hwIsOpenIssue\u0022:\u0022no\u0022,\u0022hwHasFullText\u0022:\u0022yes\u0022,\u0022hwHasPDF\u0022:\u0022yes\u0022,\u0022hwParentTitle\u0022:\u0022Journal of Neurology, Neurosurgery \u0026 Psychiatry: 86 (4)\u0022,\u0022hwElectronicPubDate\u0022:\u00222018-04-11\u0022,\u0022hwElectronicPubDateTime\u0022:\u00222018-04-11 08:13:17\u0022}}"},"user_uid":0,"customer_email":"","cartstack_siteid":"","foxycart_subdomain":"bmjpg.ecommerce.highwire.org","foxycart_always_show_cart_link":1,"hw_fc_cookie_domain":".bmj.com","jcarousel":{"ajaxPath":"\/jcarousel\/ajax\/views"},"panel_ajax_tab":{"path":"sites\/all\/modules\/contrib\/panels_ajax_tab"},"panels_ajax_pane":{"new-70fd4c70-563e-4b94-ae3b-2a97f3980c13":"{\u0022encrypted\u0022:\u0022{\\\u0022encrypted\\\u0022:\\\u00223diPpKfiLSGasV325U0\\\\\\\/0BC6NLJWMEBoA0pXcvjUYrR1OH9aidQFNHg\\\\\\\/PCpsXPQhIyCk7U5UkXYtjkIYX5OD2GR\\\\\\\/QViZqjI3V28zydfaPbg0uTdMRs2HFNA7IkCl8RXG\\\\\\\/SF00nHn6tU1hOmjG07B9kubHbsbyqje4MydEOA4eYJNZyhKyFXI5RUGnNQtwbu9kZw74gksfKizgBL8\\\\\\\/30WYhMNFpaSPvXG+TJM0PAbWJrOET8DI8Iu6D71yprG2cPB8IqmBhODll7XF92w7mxEojKUHlLm6tq9VkGQ22yv73db0syCGsyeFs4IUlpO+fo2x3LE9UtOi+kCIbRjrdtmN8Qx+y72mhMHDDjd2sEnKhQtecb15VZ\\\\\\\/8kJRMqjoCe\\\\\\\/wJMAra+\\\\\\\/f+BMb1U4GVD+Rk2lYxlR\\\\\\\/e7ZreweJ6O4FsF2eSEJeWe5uUqnMwGwAmP\\\\\\\/vrwaizSxdk6pxnGjB66fHgbTsPyQnd9pfLBrKQ0GUXUdvOv4qmPaN9Z9vJpESolpZeZkvzftkzrca2S8BHIGda4LTUnsy55FvbzpRr8CIcn1AXiS8xr7vHMkCdhD08eAb2nIb\\\\\\\/4s1Dh4hO\\\\\\\/gJTChKEMnYHrfr+UUBdglV58wMazm5C+M+DZNXUsgn2rr9BYb7YjC6vj\\\\\\\/nu2LQDXR86iMbsMDxY75FfPMj8BhvHUCAsPYmSKaULGNGP0DT8ePffE9fF\\\\\\\/iIYWsk9nlsB4v1qRIE0FtazWeawIlEZsJq5ysRdxU9YeQhsXIlCzohuZYqCPyXyhr7NrdaU5+mVK4WHn4M2VQHZSoGLI4s5N4J2kQqqhiaismS8JTveYfc1ZJqk2vfvuqdvLJjf1IXJjBYS\\\\\\\/Z\\\\\\\/neAbbNqFyKJmXaTqSMkJZMBkroOUbnT0mxxg1fSOcFSFDCc6x1Nexa9bdsp+VCrkZ6FW4uRW0Va2yrl50OeRX13ZD3v1q+H1sPRSjVKMInWm21q73M+++fE\\\\\\\/na7F10tc6KYIJrdPmO2BXEsrjTizll5srPoaF8GnS7nX4Plw6YXN8dPUUaGFT1F9\\\\\\\/Ilf+tANGi1sucCGpt5o+97W9aunLmt0wyb\\\\\\\/BB5pTceZNgfpDq9taUxqZpnpYSgkIHYgxATVW3lG0s\\\\\\\/qPf41bm57A+WLpIQ4gGWib7j\\\\\\\/HKIFoeQdVvaSoxP0s6nSMMoQaqD6qzG\\\\\\\/J3F4yTLDNxJYpkLdKPJm+VXIPHpnVElNDa2rtW9p473t96KPpjQkZWGXAlNdY\\\\\\\/LhqSeMVloJihrWdDhUBWdQOxIYBg20rDx0E92MVo7Rnqe+VH8FhEbddlnBOQfS89MylI57P5PIQsmMu9cSEOZ6eO1Ai5I7cjbYwGUUgP1+UlrGkNi1+Up6ddBU+K+bM3izPpZq5j+Fg3BL2JFuwjE0Jz2Gw1Dhj2cTdJHyEK0ylNySGr3Q47MIfnvRzz3WsLBlwP3WfobursCuZDHgCAazouqNAlIpcSLs6iRpmMwpW5scGuarwm2fg\\\\\\\/vQyQhVZixMoipHOf5GHM\\\\\\\/APsM7RsaSvXvirn6Uqd8SnTzpiLHigYCvVx+A+sY8pz6X7awC5Vs3v+sXtsBEF9xO8UJUJ0ZFG1uL03aVcPsEvfYkBLDCmx0XM4p2WXnKCRWhXPWXfAd8RKtDUv77zKrXedY6mii3hIglvwYLxLEeZ9kS9zRh3JLOXnGx3DnakQ2Dd8VftgKx9Avib7Sz7O5u\\\\\\\/zwDOR+51JMhp04oYZyIDFampE9wpcBlq+z2+vB4s6Lwg0xKcpCCviX5nDFaRi3RMBMUHOfypD1uTC4CkdL8R6Y0YKmrP4qPi+vsa24Xx1VYDY7aOsAJGfUeFD3SIgn56YQH9GvW6jxQ21zMP30U4NxKLXgok2I+DzpGenUxYYu8T0+vhMn66wGVg\\\\\\\/gxTPbemaby6cI5S9ojDskjy87mXe+KBhrio3yqh18ErUmvpiKx2mCNgDQx4MP1Cy0VaWKX93Hgb9wheUPCsddYQZSPKnQ6VVg\\\\\\\/3XfN4\\\\\\\/jmptk6JJDOzaWFCO5VQ0njBu3lrTz\\\\\\\/0K\\\\\\\/hrOFzQdvVVOtQ7kfJICsEDXDwe+1\\\\\\\/Vc\\\\\\\/JjvHyP6ReauK4y3Y3vf5IxTfGOJHzj0roFTardtvqftb4I7clExo0\\\\\\\/TV+BbOIpfBW5Ec0aY7zxjB8fHUNNExOMxBxWXUDhFOXoL1kRPeHBIatdiTEAO0FWkha5bI54z1ydrcrgKnDcDXNw1eHrOPqvLdSR\\\\\\\/XFRGO7LgkEh1OQltClvAYiV9GjG3zbfiCyxvnMPooUgbjhTsA1yjxjckKEhdpqmRUAxPr\\\\\\\/b4NWI43CcplrDA8iQTtnhHer0aPUPwLzq2Yg78IVzE1mqpWWvcEOXTk6TFJPZ4nghA\\\\\\\/O1uvzJQDQhZxBGRfkY3xykTUoBAygGi4zUBC1hC2g1YZWgs20ePYowYYtcMhka+9ZmdQeKlUtFXTt\\\\\\\/6wwsNMt0HOberPQVf6tIfYB9RVnR1VeTYbc\\\\\\\/xtJGotJNCB9WX0Kc0b9QTLUe7wUVWL5yMfjjJyxr8MbhYZ4Lyut+QD6ytVKPzruRhI8YfYU+k\\\\\\\/IYjC2jW6V1vnhU8rzcwFQF68mOuCZ\\\u0022,\\\u0022iv\\\u0022:\\\u0022yipGnwWMRqBkQ3wjtCyEcw==\\\u0022,\\\u0022salt\\\u0022:\\\u0022c79202d89cf5ca9ec5ca5117a1ecee32\\\u0022}\u0022,\u0022hmac\u0022:\u002258f00ce1b3c83fe66736cc7531ba48c046d60c4821a2000fbb1ba7ff90ee1dd6\u0022}"},"MutationObserver":{"js":"\/sites\/all\/libraries\/mutationobserver\/MutationObserver.js"},"bmjJumpLinks":{"jumplinks":["\u003Ca href=\u0022\/content\/86\/4\/431#supplementary-materials\u0022 class=\u0022button supp_jump\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003ESupplementary materials\u003C\/a\u003E","\u003Ca href=\u0022\/content\/86\/4\/431#linked-articles\u0022 class=\u0022button linked_art_jump\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003ELinked Articles\u003C\/a\u003E"],"sections":["#supplementary-materials","#linked-articles"]},"highwire_foxycart_add_to_cart_link":{"apath":"\/jnnp\/86\/4\/431.atom","text":"Buy this article (%short-price)","type":"link"},"urlIsAjaxTrusted":{"\/content\/86\/4\/431":true},"highwireResponsive":{"enquire_enabled":1,"breakpoints_configured":1,"breakpoints":{"narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (min-width: 1024px) and (min-device-width: 1024px), all (max-width: 1220px) and (max-device-width: 1220px) and (orientation:landscape)","wide":"all and (min-width: 1220px)"}}}); //--><!]]> </script> <!--[if lt IE 10]><script src="https://jnnp.bmj.com/sites/all/themes/highwire/axon/js/media.match.min.js" type="text/javascript"></script><![endif]--> <!--[if lt IE 9]><link rel="stylesheet" type="text/css" href="/sites/default/themes/bmjj/css/theme/ie-7-8.css" /><![endif]--> <script> let cookies = parseCookies(); let bmj_uuid = cookies.bmj_uuid; let bmj_ppid = cookies.bmj_ppid; window.dataLayer = window.dataLayer || []; const anonMailId = 'e3b0c44298fc1c149afbf4c8996fb92427ae41e4649b934ca495991b7852b855'; function checkUserLoginStatus(dataLayer) { const userMail = dataLayer.find((item) => item.user)?.user?.mail; if (!userMail) { return false; } return userMail !== anonMailId; } let nonAnonMailId = ((dataLayer.find(item => item.user)?.user)?.mail) === anonMailId ? null : (dataLayer.find(item => item.user)?.user)?.mail; let userId = ((dataLayer.find(item => item.user)?.user)?.['data-ics']) ?? ((dataLayer.find(item => item.user)?.user)?.mail && nonAnonMailId) ?? bmj_ppid ?? bmj_uuid; document.cookie = 'bmj_ppid=' + userId + '; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure'; googletag.cmd.push(function() { googletag.pubads().setPublisherProvidedId(userId); googletag.pubads().setTargeting("islogged", checkUserLoginStatus(dataLayer) ? "true" : "false"); googletag.enableServices(); }); window.dataLayer.push({ 'bmj_uuid': bmj_uuid }); </script> </head> <body class="html not-front not-logged-in no-sidebars page-node page-node- page-node-160406 node-type-highwire-article"> <!-- Google Tag Manager --> <noscript><iframe src="//www.googletagmanager.com/ns.html?id=GTM-54D9RV" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript> <script type="text/javascript">(function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-54D9RV');</script> <!-- End Google Tag Manager --> <div id="skip-link"> <a href="#main-content" class="element-invisible element-focusable">Skip to main content</a> </div> <div class="page" id="page"> <section class="container-fluid content-header"> <header role="banner" class="section section-header row"> <div class="zone zone-superheader"> <div class="region region-superheader"> <div class="region-inner region-superheader-inner"> <div class="region region-superheader"> <div id="block-panels-mini-jnl-template-bmjj-uid-strng" class="block block-panels-mini" class="block block-panels-mini"> <div class="content"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_template_bmjj_uid_strng"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-dfp-pane" > <div class="pane-content"> <div id="dfp-ad-top-wrapper" class="dfp-tag-wrapper"> <div id="dfp-ad-top" class="dfp-tag-wrapper"> <script type="text/javascript"> googletag.cmd.push(function() { googletag.display("dfp-ad-top"); }); </script> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div><!-- /.region-superheader --> </div><!-- /.zone-super-header --> <div class="site-info mobile-hidden"> </div><!-- /.site-info --> <div class="zone zone-header row mobile-hidden"> <div class="region region-header"> <div class="region-inner region-header-inner"> </div> </div><!-- ./region-header --> </div><!-- /.zone-header --> </header> <!-- /.section-header --> <section class="row visible-sm visible-md visible-lg header header-platform mobile-hidden"> <div class="col-narrow-3 col-normal-3 col-large-3 logo-bmj"> <div class="l-inline"> <p class="logo-bmj-journals"><a href="http://journals.bmj.com/" title="BMJ Journals"><img src="/sites/default/themes/bmjj/img/logos/logo-bmj-journals.svg" title="BMJ Journals" alt="BMJ Journals"/></a></p> </div> </div> <div class="col-narrow-9 col-normal-9 col-large-9 no-right-padding"> <div class="region region-top"> <div class="region-inner"> <div class="region region-platmenu"> <div id="block-menu-menu-platform-menu" class="block block-menu" class="block block-menu"> <div class="content"> <ul class="menu"><li class="first leaf"><a href="/subscribe" data-hide-link-title="0" class="header-subscribe-link" data-icon-position="">Subscribe</a></li> <li class="leaf"><a href="/" id="menu-login" class="drop-menu link-icon-right link-icon"><span class="title">Log In</span> <span class="icon icon-arrow-down"></span></a> <a href="# " class="menu-attach-block-drop-link external expand-on-click" data-block-id="panels_mini|challenge_opportunity_pane_dropdown" id="<front>-drop-link-728" data-icon-position="" data-hide-link-title="0">More</a><div class="menu-attach-block-wrapper"> <div id="block-panels-mini-challenge-opportunity-pane-dropdown" class="block block-panels-mini article-login bmjj-login" class="block block-panels-mini"> <div class="content"> <div class="panel-display panel-1col clearfix" id="mini-panel-challenge_opportunity_pane_dropdown-2"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-bmjj-society-logins society-logins" > <div class="pane-content"> <span class="ui-button ui-state-default ui-dialog-titlebar-close" title="close"></span><div class="shib-login-link"><a href="/login/shibboleth?subcode=bmjjournals&env=prod&uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via Institution</a></div><div class="openathens-login-link"><a href="https://openathens-sp.highwire.org/session/init?entityID=https%3A//idp.eduserv.org.uk/openathens&hw-shib-return-uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431&subcode=bmjjournals" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via OpenAthens</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-opportunity-challenge" > <div class="pane-content"> <div class='opportunity-challenge-login'><h3>Log in using your username and password</h3><div class="drupal-login compact"><form action="/content/86/4/431" method="post" id="highwire-user-login--4" accept-charset="UTF-8"><div><div id="edit-customtext--4" class="form-item form-item-label-before form-type-item"> <span class="customtext">For personal accounts OR managers of institutional accounts</span> </div> <div class="form-item form-item-label-invisible form-type-textfield form-item-name"> <label class="element-invisible" for="edit-name--4">Username <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Username" type="text" id="edit-name--4" name="name" value="" size="30" maxlength="60" class="form-text required" /> </div> <div class="form-item form-item-label-invisible form-type-password form-item-pass"> <label class="element-invisible" for="edit-pass--4">Password <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Password" type="password" id="edit-pass--4" name="pass" size="30" maxlength="128" class="form-text required" /> </div> <input type="hidden" name="form_build_id" value="form-SBE3uQASzm_7i9K8RmagcPUUYCf0f6p2mYVTmCj1SsA" /> <input type="hidden" name="form_id" value="highwire_user_login" /> <div class="bmjj-reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot your log in details?</a><a href="/user/register?destination=node/160406" class="" data-icon-position="" data-hide-link-title="0">Register a new account?</a></div><div class="form-actions form-wrapper" id="edit-actions--4"><input type="submit" id="edit-submit--4" name="op" value="Log in" class="form-submit" /></div><div class="reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot</a> your user name or password?</div></div></form></div></div> </div> </div> </div> </div> </div> </div> </div> </div> </li> <li class="leaf"><a href="/cart" class="link-icon-right link-icon"><span class="title">Basket</span> <span class="icon icon-basket"></span></a></li> <li class="last leaf"><a href="/search" id="menu-search" class="drop-menu link-icon-right link-icon"><span class="title">Search</span> <span class="icon icon-search"></span></a> <a href="# " class="menu-attach-block-drop-link external expand-on-click" data-block-id="panels_mini|jnl_template_bmjj_search_box" id="search-drop-link-729" data-icon-position="" data-hide-link-title="0">More</a><div class="menu-attach-block-wrapper"> <div id="block-panels-mini-jnl-template-bmjj-search-box" class="block block-panels-mini" class="block block-panels-mini"> <div class="content"> <div class="panel-display one-layout " id="mini-panel-jnl_template_bmjj_search_box-1"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-seach-quicksearch block-search pull-left" > <div class="pane-content"> <form class="highwire-quicksearch button-style-mini button-style-mini" action="/content/86/4/431" method="post" id="highwire-search-quicksearch-form-1" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-keywords"> <label class="element-invisible" for="search_rightsidebar_keywords_1272674880">Search for this keyword </label> <input placeholder="search" type="text" id="search_rightsidebar_keywords_1272674880" name="keywords" value="" size="60" maxlength="128" class="form-text" /> </div> <input data-icon-only="1" data-font-icon="icon-search" data-icon-position="after" type="submit" id="search_rightsidebar_submit_1046425776" name="op" value="Search" class="form-submit" /><input type="hidden" name="form_build_id" value="form-bk578QkG7iihhkRpq4S2DZ2J3oncwCrMBoi2FeMzAoA" /> <input type="hidden" name="form_id" value="highwire_search_quicksearch_form_1" /> </div></form> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-6 pull-right advanced-search-link" > <div class="pane-content"> <a href="/search">Advanced search</a> </div> </div> </div> </div> </div> </div> </div> </div> </li> </ul> </div> </div> </div> </div> </div><!-- /.region-top --> </div> </section> <div class="row header header-journal"> <div class="col-mobile-7 col-narrow-2 col-normal-4 logo-journal"> <a href="/"><img src="https://resources.bmj.com/repository/journals-network-project/images/journal-logos/logo-jnnp.svg" alt="Journal of Neurology, Neurosurgery & Psychiatry" id="logo-img"></a> </div> <div class="col-mobile-5 col-narrow-10 col-normal-8 no-right-padding nav-journal"> <div class="region region-journmenu"> <div id="block-system-main-menu" class="block block-system mobile-hidden block-menu" class="block block-system mobile-hidden block-menu"> <div class="content"> <ul class="menu"><li class="first leaf"><a href="/content/early/recent" class="" data-icon-position="" data-hide-link-title="0">Latest content</a></li> <li class="leaf"><a href="/content/current" class="" data-icon-position="" data-hide-link-title="0">Current issue</a></li> <li class="leaf"><a href="/content/by/year" class="" data-icon-position="" data-hide-link-title="0">Archive</a></li> <li class="leaf"><a href="https://jnnp.bmj.com/pages/jnnp-100-a-centenary-of-publishing-neuroscience-achievement/" class="" data-icon-position="" data-hide-link-title="0">JNNP 100</a></li> <li class="leaf"><a href="http://jnnp.bmj.com/pages/authors/" class="" data-icon-position="" data-hide-link-title="0">Authors</a></li> <li class="leaf"><a href="https://jnnpbmj.podbean.com/" class="" data-icon-position="" data-hide-link-title="0">Podcasts</a></li> <li class="last leaf"><a href="http://jnnp.bmj.com/pages/about/" class="" data-icon-position="" data-hide-link-title="0">About</a></li> </ul> </div> </div> <div id="block-panels-mini-mobile-slide-out-menu" class="block block-panels-mini mobile-only" class="block block-panels-mini mobile-only"> <div class="content"> <div class="panel-display panel-1col clearfix" id="mini-panel-mobile_slide_out_menu"> <div class="panel-panel panel-col"> <div><div id="" class="highwire-responsive-toggle-group"><div class="panel-pane pane-panels-mini pane-jnl-template-bmjj-search-box" > <h2 class="pane-title"><span class="icon-search"></span></h2> <div class="pane-content"> <div class="panel-display one-layout " id="mini-panel-jnl_template_bmjj_search_box"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-seach-quicksearch block-search pull-left" > <div class="pane-content"> <form class="highwire-quicksearch button-style-mini button-style-mini" action="/content/86/4/431" method="post" id="highwire-search-quicksearch-form-0" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-keywords"> <label class="element-invisible" for="search_rightsidebar_keywords_1027820032">Search for this keyword </label> <input placeholder="search" type="text" id="search_rightsidebar_keywords_1027820032" name="keywords" value="" size="60" maxlength="128" class="form-text" /> </div> <input data-icon-only="1" data-font-icon="icon-search" data-icon-position="after" type="submit" id="search_rightsidebar_submit_1472803902" name="op" value="Search" class="form-submit" /><input type="hidden" name="form_build_id" value="form-ALi2k8SHu4Y0pBUgym_r3Qp3C0sF-izW3UWTrlR8O8E" /> <input type="hidden" name="form_id" value="highwire_search_quicksearch_form_0" /> </div></form> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-5 pull-right advanced-search-link" > <div class="pane-content"> <a href="/search">Advanced search</a> </div> </div> </div> </div> </div> </div> </div> <div class="panel-pane pane-block pane-menu-menu-mobile-slideout-menu pane-menu" > <h2 class="pane-title"><span class="icon-menu"></span></h2> <div class="pane-content"> <ul class="menu"><li class="first leaf"><a href="/" class="menu-close link-icon-only link-icon"><span class="icon icon-close"></span> <span class="title element-invisible">Close</span></a> <a href="# " class="menu-attach-block-drop-link external expand-on-click" data-block-id="panels_mini|mobile_slide_out_autobot_menu" id="<front>-drop-link-781" data-icon-position="" data-hide-link-title="0">More</a><div class="menu-attach-block-wrapper"> <div id="block-panels-mini-mobile-slide-out-autobot-menu" class="block block-panels-mini" class="block block-panels-mini"> <div class="content"> <div class="panel-display one-layout " id="mini-panel-mobile_slide_out_autobot_menu"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-menu-tree pane-main-menu" > <h2 class="pane-title">Main menu</h2> <div class="pane-content"> <div class="menu-block-wrapper menu-block-ctools-main-menu-1 menu-name-main-menu parent-mlid-main-menu:0 menu-level-1"> <ul class="menu"><li class="first leaf menu-mlid-15201"><a href="/content/early/recent" class="" data-icon-position="" data-hide-link-title="0">Latest content</a></li> <li class="leaf menu-mlid-15202"><a href="/content/current" class="" data-icon-position="" data-hide-link-title="0">Current issue</a></li> <li class="leaf menu-mlid-15203"><a href="/content/by/year" class="" data-icon-position="" data-hide-link-title="0">Archive</a></li> <li class="leaf menu-mlid-15204"><a href="https://jnnp.bmj.com/pages/jnnp-100-a-centenary-of-publishing-neuroscience-achievement/" class="" data-icon-position="" data-hide-link-title="0">JNNP 100</a></li> <li class="leaf menu-mlid-15205"><a href="http://jnnp.bmj.com/pages/authors/" class="" data-icon-position="" data-hide-link-title="0">Authors</a></li> <li class="leaf menu-mlid-15206"><a href="https://jnnpbmj.podbean.com/" class="" data-icon-position="" data-hide-link-title="0">Podcasts</a></li> <li class="last leaf menu-mlid-15207"><a href="http://jnnp.bmj.com/pages/about/" class="" data-icon-position="" data-hide-link-title="0">About</a></li> </ul></div> </div> </div> </div> </div> </div> </div> </div> </div> </li> <li class="leaf"><a href="/subscribe" data-hide-link-title="0" class="callout-link" data-icon-position="">Subscribe</a></li> <li class="leaf"><a href="/" class="mobile-drop-down callout-link link-icon-right link-icon"><span class="title">Log in</span> <span class="icon icon-plus"></span></a> <a href="# " class="menu-attach-block-drop-link external expand-on-click" data-block-id="panels_mini|jnl_template_bmjj_login" id="<front>-drop-link-780" data-icon-position="" data-hide-link-title="0">More</a><div class="menu-attach-block-wrapper"> <div id="block-panels-mini-jnl-template-bmjj-login" class="block block-panels-mini" class="block block-panels-mini"> <div class="content"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_template_bmjj_login"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-bmjj-society-logins society-logins opportunity-challenge-login" > <div class="pane-content"> <span class="ui-button ui-state-default ui-dialog-titlebar-close" title="close"></span><div class="shib-login-link"><a href="/login/shibboleth?subcode=bmjjournals&env=prod&uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via Institution</a></div><div class="openathens-login-link"><a href="https://openathens-sp.highwire.org/session/init?entityID=https%3A//idp.eduserv.org.uk/openathens&hw-shib-return-uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431&subcode=bmjjournals" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via OpenAthens</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-opportunity-challenge" > <div class="pane-content"> <div class='opportunity-challenge-login'><h3>Log in using your username and password</h3><div class="drupal-login compact"><form action="/content/86/4/431" method="post" id="highwire-user-login--3" accept-charset="UTF-8"><div><div id="edit-customtext--3" class="form-item form-item-label-before form-type-item"> <span class="customtext">For personal accounts OR managers of institutional accounts</span> </div> <div class="form-item form-item-label-invisible form-type-textfield form-item-name"> <label class="element-invisible" for="edit-name--3">Username <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Username" type="text" id="edit-name--3" name="name" value="" size="30" maxlength="60" class="form-text required" /> </div> <div class="form-item form-item-label-invisible form-type-password form-item-pass"> <label class="element-invisible" for="edit-pass--3">Password <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Password" type="password" id="edit-pass--3" name="pass" size="30" maxlength="128" class="form-text required" /> </div> <input type="hidden" name="form_build_id" value="form-hIDqSeTH2RRU9H0gR6WcshiSnvqjiuMDx4laQKxEb6c" /> <input type="hidden" name="form_id" value="highwire_user_login" /> <div class="bmjj-reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot your log in details?</a><a href="/user/register?destination=node/160406" class="" data-icon-position="" data-hide-link-title="0">Register a new account?</a></div><div class="form-actions form-wrapper" id="edit-actions--3"><input type="submit" id="edit-submit--3" name="op" value="Log in" class="form-submit" /></div><div class="reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot</a> your user name or password?</div></div></form></div></div> </div> </div> </div> </div> </div> </div> </div> </div> </li> <li class="last leaf"><a href="http://journals.bmj.com/" data-hide-link-title="0" class="bmj-link" data-icon-position="">BMJ Journals</a></li> </ul> </div> </div> </div></div> </div> </div> </div> </div> </div> </div><!-- /.region-top --> </div> </section> <section role="main" class="section section-content container-fluid"> <div class="crumb-navigation"> <div class="row"> <div class="col-mobile-12 col-narrow-9 col-normal-9 col-wide-10 breadcrumbs"> <h2 class="element-invisible">You are here</h2><div class="item-list"><ul class="breadcrumb"><li class="first"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Home</a></li> <li><a href="/content/by/year" class="" data-icon-position="" data-hide-link-title="0">Archive</a></li> <li><a href="/content/86/4" class="" data-icon-position="" data-hide-link-title="0">Volume 86, Issue 4 </a></li> <li class="last"><span class="active">Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study</span></li> </ul></div> </div> <div class="mobile-hidden col-narrow-3 col-normal-3 col-wide-2 email-alerts"> <span> <a href="https://myaccount.bmj.com/myaccount/signup.html?regService=etoc-alerts&corpusCode=jnnp&fwdUrl=https://jnnp.bmj.com/" class="email-alerts-label"><i class="icon icon-article-alerts"></i>Email alerts</a> </span> </div> </div> </div> <div class="container"> <div class="zone zone-content row"> <div class="region region-content col-narrow-12"> <div class="region-inner region-content-inner"> <a id="main-content"></a> <div class="region region-content"> <div id="block-system-main" class="block block-system" class="block block-system"> <div class="content"> <div class="panel-display two-layout " > <div class="panel-row-wrapper panel-row-first row"> <div class="top-wrapper col-narrow-12"> <div class="panel-panel panel-region-top"> <div class="inside"><div class="panel-pane pane-panels-mini pane-article-tabset-mobile mobile-only" id="mobile-article-tab-container"> <div class="pane-content"> <div class="panel-display two-layout " id="mini-panel-article_tabset_mobile_"> <div class="panel-row-wrapper row"> <div class="left-wrapper col-mobile-6"> <div class="panel-panel panel-region-left"> <div class="inside"><div class="panel-pane pane-bmjj-mob-tab-title" id="mobile-tab-title"> <div class="pane-content"> <p><span class="icon-article-text"></span>Article Text</p> </div> </div> </div> </div> </div> <div class="right-wrapper col-mobile-6"> <div class="panel-panel panel-region-right"> <div class="inside"><div class="panel-pane pane-bmjj-mobile-article-menu" > <div class="pane-content"> <a href="#block-system-main" class="mobile-article-tab" data-icon-position="" data-hide-link-title="0">Article menu <span class="icon-plus icon-toggle"></span></a><div class="mobile-art-drop-down"></div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> <div class="panel-row-wrapper row relative" id="article-top"> <div class="left-wrapper col-narrow-2 col-normal-1 col-wide-1 tab-pane"> <div class="panel-panel panel-region-left"> <div class="inside"><div class="panel-pane pane-highwire-panel-tabs pane-panels-ajax-tab-tabs nav nav-tabs nav-stacked articleToolbar mobile-hidden" id="nav-tabs"> <div class="pane-content"> <div class="item-list"><ul class="tabs inline panels-ajax-tab"><li class="active first"><a href="/content/86/4/431" class="panels-ajax-tab-tab" data-panel-name="jnl_template_bmjj_tab_art" data-target-id="highwire_article_tabs" data-entity-context="node:160406" data-trigger="" data-url-enabled="1"><span class="icon-article-text"></span>Article <br/>Text</a><a href="/panels_ajax_tab/jnl_template_bmjj_tab_art/node:160406/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li> <li class=""><a href="/content/86/4/431.info" class="panels-ajax-tab-tab" data-panel-name="jnl_template_bmjj_art_info" data-target-id="highwire_article_tabs" data-entity-context="node:160406" data-trigger="info" data-url-enabled="1"><span class="icon-article-info"></span>Article <br/>info</a><a href="/panels_ajax_tab/jnl_template_bmjj_art_info/node:160406/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li> <li class=""><a href="/content/86/4/431.citation-tools" class="panels-ajax-tab-tab" data-panel-name="jnl_template_bmjj_cite_tool" data-target-id="highwire_article_tabs" data-entity-context="node:160406" data-trigger="citation-tools" data-url-enabled="1"><span class="icon-citation-tools"></span>Citation <br/>Tools</a><a href="/panels_ajax_tab/jnl_template_bmjj_cite_tool/node:160406/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li> <li class=""><a href="/content/86/4/431.share" class="panels-ajax-tab-tab" data-panel-name="jnl_template_bmjj_share" data-target-id="highwire_article_tabs" data-entity-context="node:160406" data-trigger="share" data-url-enabled="1"><span class="icon-share"></span>Share</a><a href="/panels_ajax_tab/jnl_template_bmjj_share/node:160406/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li> <li class=""><a href="/content/86/4/431.responses" class="panels-ajax-tab-tab" data-panel-name="jnl_template_bmjj_tab_elets" data-target-id="highwire_article_tabs" data-entity-context="node:160406" data-trigger="responses" data-url-enabled="1"><span class="icon-responses"></span>Rapid Responses</a><a href="/panels_ajax_tab/jnl_template_bmjj_tab_elets/node:160406/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li> <li class=""><a href="/content/86/4/431.altmetrics" class="panels-ajax-tab-tab" data-panel-name="jnl_template_bmjj_tab_altmetrics" data-target-id="highwire_article_tabs" data-entity-context="node:160406" data-trigger="altmetrics" data-url-enabled="1"><span class="icon-article-stats"></span>Article <br/>metrics</a><a href="/panels_ajax_tab/jnl_template_bmjj_tab_altmetrics/node:160406/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li> <li class=" last"><a href="/content/86/4/431.alerts" class="panels-ajax-tab-tab" data-panel-name="jnl_template_bmjj_art_alert" data-target-id="highwire_article_tabs" data-entity-context="node:160406" data-trigger="alerts" data-url-enabled="1"><span class="icon-article-alerts"></span>Alerts</a><a href="/panels_ajax_tab/jnl_template_bmjj_art_alert/node:160406/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li> </ul></div> </div> </div> </div> </div> </div> <div class="right-wrapper col-narrow-9 col-normal-10 col-wide-10 article-pane panel-region-main"> <div class="panel-panel panel-region-right"> <div class="inside"><div class="panel-pane pane-bmjj-challenge-modal col-mobile-2 col-narrow-1 pull-right " > <div class="pane-content"> <a href="" class="" data-icon-position="" data-hide-link-title="0"><a href="#" id="chal-modal" class="article-pdf-download"><img alt="Download PDF" src="/sites/default/themes/bmjj/img/icon-pdf.png" /><strong>PDF</strong></a></a> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-entity-field pane-node-field-highwire-article-cat article-category col-narrow-9 col-normal-10" > <div class="pane-content"> <div class="field field-name-field-highwire-article-cat field-type-text field-label-hidden"><div class="field-items"><div class="field-item even">Neurodegeneration</div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-entity-field pane-node-field-highwire-a-series-title article-series-title col-narrow-10" > <div class="pane-content"> <div class="field field-name-field-highwire-a-series-title field-type-text-long field-label-hidden"><div class="field-items"><div class="field-item even">Research paper</div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-article-citation col-mobile-10 col-narrow-10 col-normal-11 article-title" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node160406" data-node-nid="160406" id="node-160406--2307687701" data-pisa="jnnp;86/4/431" data-pisa-master="jnnp;jnnp-2014-308094" data-apath="/jnnp/86/4/431.atom"><cite class="highwire-cite highwire-cite-highwire-article highwire-citation-bmjj-title clearfix"> <div class="highwire-cite-title">Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study</div> <span class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="jnnp;jnnp-2014-308094" data-atom-uri="/jnnp/86/4/431.atom" data-request-view="full"></span></span> </cite> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-panel-tabs-container col-narrow-12 clear" > <div class="pane-content"> <div data-panels-ajax-tab-preloaded="jnl_template_bmjj_tab_art" id="panels-ajax-tab-container-highwire_article_tabs" class="panels-ajax-tab-container"><div class="panels-ajax-tab-loading" style ="display:none"><img class="loading" src="https://jnnp.bmj.com/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif" alt="Loading" title="Loading" /></div><div class="panels-ajax-tab-wrap-jnl_template_bmjj_tab_art"><div class="panel-display panel-1col clearfix" > <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-markup author-affiliates col-narrow-12 author-affiliates-corresp article" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div xmlns:xhtml="http://www.w3.org/1999/xhtml" class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">Kevin T Ong</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1">1</a>, </li><li class="contributor" id="contrib-2"><span class="name">Victor L Villemagne</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1">1</a><span class="xref-sep">,</span><a id="xref-aff-2-1" class="xref-aff" href="#aff-2">2</a>, </li><li class="contributor" id="contrib-3"><span class="name">Alex Bahar-Fuchs</span><a id="xref-aff-1-3" class="xref-aff" href="#aff-1">1</a><span class="xref-sep">,</span><a id="xref-aff-3-1" class="xref-aff" href="#aff-3">3</a>, </li><li class="contributor" id="contrib-4"><span class="name">Fiona Lamb</span><a id="xref-aff-1-4" class="xref-aff" href="#aff-1">1</a>, </li><li class="contributor" id="contrib-5"><span class="name">Narelle Langdon</span><a id="xref-aff-1-5" class="xref-aff" href="#aff-1">1</a>, </li><li class="contributor" id="contrib-6"><span class="name">Ana M Catafau</span><a id="xref-aff-4-1" class="xref-aff" href="#aff-4">4</a>, </li><li class="contributor" id="contrib-7"><span class="name">Andrew W Stephens</span><a id="xref-aff-4-2" class="xref-aff" href="#aff-4">4</a>, </li><li class="contributor" id="contrib-8"><span class="name">John Seibyl</span><a id="xref-aff-5-1" class="xref-aff" href="#aff-5">5</a>, </li><li class="contributor" id="contrib-9"><span class="name">Ludger M Dinkelborg</span><a id="xref-aff-4-3" class="xref-aff" href="#aff-4">4</a>, </li><li class="contributor" id="contrib-10"><span class="name">Cornelia B Reininger</span><a id="xref-aff-6-1" class="xref-aff" href="#aff-6">6</a>, </li><li class="contributor" id="contrib-11"><span class="name">Barbara Putz</span><a id="xref-aff-6-2" class="xref-aff" href="#aff-6">6</a>, </li><li class="contributor" id="contrib-12"><span class="name">Beate Rohde</span><a id="xref-aff-6-3" class="xref-aff" href="#aff-6">6</a>, </li><li class="contributor" id="contrib-13"><span class="name">Colin L Masters</span><a id="xref-aff-2-2" class="xref-aff" href="#aff-2">2</a>, </li><li class="last" id="contrib-14"><span class="name">Christopher C Rowe</span><a id="xref-aff-1-6" class="xref-aff" href="#aff-1">1</a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address> <sup>1</sup><span class="addr-line">Department of Nuclear Medicine</span>, <span class="institution">Centre for PET, Austin Health</span>, <span class="addr-line">Heidelberg, Victoria</span>, Australia</address></li><li class="aff"><a id="aff-2" name="aff-2"></a><address> <sup>2</sup><span class="institution">The Florey Institute of Neuroscience and Mental Health, The University of Melbourne</span>, <span class="addr-line">Parkville, Victoria</span>, Australia</address></li><li class="aff"><a id="aff-3" name="aff-3"></a><address> <sup>3</sup><span class="institution">Centre for Research on Aging, Health, and Wellbeing, The Australian National University</span>, <span class="addr-line">Acton, Australian Capital Territory</span>, Australia</address></li><li class="aff"><a id="aff-4" name="aff-4"></a><address> <sup>4</sup><span class="institution">Piramal Imaging GmbH</span>, <span class="addr-line">Berlin</span>, Germany</address></li><li class="aff"><a id="aff-5" name="aff-5"></a><address> <sup>5</sup><span class="institution">Molecular NeuroImaging, L.L.C.</span>, <span class="addr-line">New Haven, Connecticut</span>, USA</address></li><li class="aff"><a id="aff-6" name="aff-6"></a><address> <sup>6</sup><span class="institution">Bayer Healthcare</span>, <span class="addr-line">Berlin</span>, Germany</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1"><span class="corresp-label">Correspondence to</span> Professor Christopher Rowe, Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; <span class="em-link"><span class="em-addr">Christopher.Rowe{at}austin.org.au</span></span> </li></ol></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-markup abstract-with-bc" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><div id="sec-1" class="subsection"> <p id="p-1"><strong>Background</strong> We assessed the clinical utility of β-amyloid (Aβ) imaging with <sup>18</sup>F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time.</p> </div><div id="sec-2" class="subsection"> <p id="p-2"><strong>Methods</strong> 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <−1.5.</p> </div><div id="sec-3" class="subsection"> <p id="p-3"><strong>Results</strong> At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB−, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB− developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB− had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−.</p> </div><div id="sec-4" class="subsection"> <p id="p-4"><strong>Conclusions</strong> <sup>18</sup>F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline.</p> </div><div id="sec-5" class="subsection"> <p id="p-5"><strong>Trial registration number</strong> NCT01138111.</p> </div> </div><ul class="kwd-group"><li class="kwd">ALZHEIMER'S DISEASE</li><li class="kwd">AMYLOID</li><li class="kwd">COGNITION</li><li class="kwd">DEMENTIA</li><li class="kwd">MRI</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-dfp-pane oas-ads oas-ads-mid pull-right" > <div class="pane-content"> <div id="dfp-ad-mpu-wrapper" class="dfp-tag-wrapper"> <div id="dfp-ad-mpu" class="dfp-tag-wrapper"> <script type="text/javascript"> googletag.cmd.push(function() { googletag.display("dfp-ad-mpu"); }); </script> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-1" > <div class="pane-content"> <p><a href="https://doi.org/10.1136/jnnp-2014-308094" target="_new">https://doi.org/10.1136/jnnp-2014-308094</a></p> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-altmetrics" > <h2 class="pane-title">Statistics from Altmetric.com</h2> <div class="pane-content"> <div data-badge-details="right" data-badge-type="medium-donut" data-doi="10.1136/jnnp-2014-308094" data-hide-no-mentions="true" class="altmetric-embed"></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-bmjj-jumplinks" > <div class="pane-content"> <div class="highwire-list-wrapper"><div class="highwire-list"><ul></ul></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-2 permissions-box" > <h2 class="pane-title">Request Permissions</h2> <div class="pane-content"> <p>If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.</p> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-ajax-pane-content permissions-box pane-highwire-permission-link" id="request-permissions"> <h2 class="pane-title"><span class='panels-ajax-pane-title' data-pid='new-70fd4c70-563e-4b94-ae3b-2a97f3980c13'></span></h2> <div class="pane-content"> <div class='panels-ajax-pane panels-ajax-pane-new-70fd4c70-563e-4b94-ae3b-2a97f3980c13' data-pid='new-70fd4c70-563e-4b94-ae3b-2a97f3980c13'></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-markup" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><ul class="kwd-group"><li class="kwd"><a href="/keyword/alzheimers-disease" class="hw-term hw-article-keyword hw-article-keyword-alzheimers-disease" rel="nofollow">ALZHEIMER'S DISEASE</a></li><li class="kwd"><a href="/keyword/amyloid" class="hw-term hw-article-keyword hw-article-keyword-amyloid" rel="nofollow">AMYLOID</a></li><li class="kwd"><a href="/keyword/cognition" class="hw-term hw-article-keyword hw-article-keyword-cognition" rel="nofollow">COGNITION</a></li><li class="kwd"><a href="/keyword/dementia" class="hw-term hw-article-keyword hw-article-keyword-dementia" rel="nofollow">DEMENTIA</a></li><li class="kwd"><a href="/keyword/mri" class="hw-term hw-article-keyword hw-article-keyword-mri" rel="nofollow">MRI</a></li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="https://jnnp.bmj.com/content/86/4/431.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-markup footnotes" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-template-bmjj-challenge article-login" > <h2 class="pane-title">Read the full text or download the PDF:</h2> <div class="pane-content"> <div class="panel-display three-layout " id="mini-panel-jnl_template_bmjj_challenge"> <div class="panel-row-wrapper row"> <div class="left-wrapper col-narrow-12 col-normal-4"> <div class="panel-panel panel-region-left"> <div class="inside"><div class="panel-pane pane-add-to-cart" > <div class="pane-content"> <span class="highwire-foxycart-add-to-cart-ahah highwire-foxycart-add-to-cart-ahah" data-text="Buy this article (%short-price)" data-apath="/jnnp/86/4/431.atom" data-type="link" data-font-icon="" data-parent-id="136290"></span> </div> </div> </div> </div> </div> <div class="middle-wrapper col-narrow-12 col-normal-4"> <div class="panel-panel panel-region-middle"> <div class="inside"><div class="panel-pane pane-bmjj-article-subscribe-button" > <div class="pane-content"> <a href="/subscribe" class="btn btn-default btn-lg" data-icon-position="" data-hide-link-title="0">Subscribe</a> </div> </div> </div> </div> </div> <div class="right-wrapper col-narrow-12 col-normal-4"> <div class="panel-panel panel-region-right article-login"> <div class="inside"><div class="panel-pane pane-custom pane-3" > <div class="pane-content"> <button type="submit" class="btn btn-default btn-lg" id="sign-in" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false" aria-hidden="true">Log in <svg class="icon icon-white icon-arrow-down"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="/sites/default/themes/bmjj/img/defs.svg#icon-arrow-down"></use></svg></button> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-challenge-opportunity-pane-dropdown" > <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-challenge_opportunity_pane_dropdown"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-bmjj-society-logins society-logins" > <div class="pane-content"> <span class="ui-button ui-state-default ui-dialog-titlebar-close" title="close"></span><div class="shib-login-link"><a href="/login/shibboleth?subcode=bmjjournals&env=prod&uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via Institution</a></div><div class="openathens-login-link"><a href="https://openathens-sp.highwire.org/session/init?entityID=https%3A//idp.eduserv.org.uk/openathens&hw-shib-return-uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431&subcode=bmjjournals" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via OpenAthens</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-opportunity-challenge" > <div class="pane-content"> <div class='opportunity-challenge-login'><h3>Log in using your username and password</h3><div class="drupal-login compact"><form action="/content/86/4/431" method="post" id="highwire-user-login" accept-charset="UTF-8"><div><div id="edit-customtext" class="form-item form-item-label-before form-type-item"> <span class="customtext">For personal accounts OR managers of institutional accounts</span> </div> <div class="form-item form-item-label-invisible form-type-textfield form-item-name"> <label class="element-invisible" for="edit-name">Username <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Username" type="text" id="edit-name" name="name" value="" size="30" maxlength="60" class="form-text required" /> </div> <div class="form-item form-item-label-invisible form-type-password form-item-pass"> <label class="element-invisible" for="edit-pass">Password <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Password" type="password" id="edit-pass" name="pass" size="30" maxlength="128" class="form-text required" /> </div> <input type="hidden" name="form_build_id" value="form-_z5Y-wbpdu6NvG0jJYzVJt7pDqf04ZOcjJDIW_Am4kI" /> <input type="hidden" name="form_id" value="highwire_user_login" /> <div class="bmjj-reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot your log in details?</a><a href="/user/register?destination=node/160406" class="" data-icon-position="" data-hide-link-title="0">Register a new account?</a></div><div class="form-actions form-wrapper" id="edit-actions"><input type="submit" id="edit-submit" name="op" value="Log in" class="form-submit" /></div><div class="reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot</a> your user name or password?</div></div></form></div></div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> </div> </div> </div> </div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-template-bmjj-challenge article-login col-narrow-12 clear hidden" > <h2 class="pane-title">Read the full text or download the PDF:</h2> <div class="pane-content"> <div class="panel-display three-layout " id="mini-panel-jnl_template_bmjj_challenge-1"> <div class="panel-row-wrapper row"> <div class="left-wrapper col-narrow-12 col-normal-4"> <div class="panel-panel panel-region-left"> <div class="inside"><div class="panel-pane pane-add-to-cart" > <div class="pane-content"> <span class="highwire-foxycart-add-to-cart-ahah highwire-foxycart-add-to-cart-ahah" data-text="Buy this article (%short-price)" data-apath="/jnnp/86/4/431.atom" data-type="link" data-font-icon="" data-parent-id="136290"></span> </div> </div> </div> </div> </div> <div class="middle-wrapper col-narrow-12 col-normal-4"> <div class="panel-panel panel-region-middle"> <div class="inside"><div class="panel-pane pane-bmjj-article-subscribe-button" > <div class="pane-content"> <a href="/subscribe" class="btn btn-default btn-lg" data-icon-position="" data-hide-link-title="0">Subscribe</a> </div> </div> </div> </div> </div> <div class="right-wrapper col-narrow-12 col-normal-4"> <div class="panel-panel panel-region-right article-login"> <div class="inside"><div class="panel-pane pane-custom pane-4" > <div class="pane-content"> <button type="submit" class="btn btn-default btn-lg" id="sign-in" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false" aria-hidden="true">Log in <svg class="icon icon-white icon-arrow-down"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="/sites/default/themes/bmjj/img/defs.svg#icon-arrow-down"></use></svg></button> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-challenge-opportunity-pane-dropdown" > <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-challenge_opportunity_pane_dropdown-1"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-bmjj-society-logins society-logins" > <div class="pane-content"> <span class="ui-button ui-state-default ui-dialog-titlebar-close" title="close"></span><div class="shib-login-link"><a href="/login/shibboleth?subcode=bmjjournals&env=prod&uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via Institution</a></div><div class="openathens-login-link"><a href="https://openathens-sp.highwire.org/session/init?entityID=https%3A//idp.eduserv.org.uk/openathens&hw-shib-return-uri=https%3A//jnnp.bmj.com/accallback/content%25252F86%25252F4%25252F431&subcode=bmjjournals" class="button society-login-link" data-icon-position="" data-hide-link-title="0">Log in via OpenAthens</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-opportunity-challenge" > <div class="pane-content"> <div class='opportunity-challenge-login'><h3>Log in using your username and password</h3><div class="drupal-login compact"><form action="/content/86/4/431" method="post" id="highwire-user-login--2" accept-charset="UTF-8"><div><div id="edit-customtext--2" class="form-item form-item-label-before form-type-item"> <span class="customtext">For personal accounts OR managers of institutional accounts</span> </div> <div class="form-item form-item-label-invisible form-type-textfield form-item-name"> <label class="element-invisible" for="edit-name--2">Username <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Username" type="text" id="edit-name--2" name="name" value="" size="30" maxlength="60" class="form-text required" /> </div> <div class="form-item form-item-label-invisible form-type-password form-item-pass"> <label class="element-invisible" for="edit-pass--2">Password <span class="form-required" title="This field is required.">*</span></label> <input placeholder="Password" type="password" id="edit-pass--2" name="pass" size="30" maxlength="128" class="form-text required" /> </div> <input type="hidden" name="form_build_id" value="form-cHtOz-x25zbDztK_eZwC2c-VilEr8Pfg-wdVWYT2luQ" /> <input type="hidden" name="form_id" value="highwire_user_login" /> <div class="bmjj-reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot your log in details?</a><a href="/user/register?destination=node/160406" class="" data-icon-position="" data-hide-link-title="0">Register a new account?</a></div><div class="form-actions form-wrapper" id="edit-actions--2"><input type="submit" id="edit-submit--2" name="op" value="Log in" class="form-submit" /></div><div class="reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot</a> your user name or password?</div></div></form></div></div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> </div> </div> <a href="#" id="article-bottom"></a> </div> <div class="col-narrow-1 mobile-hidden back-top" id="back-top"> <div class="panel-panel panel-region-left"> <div class="inside" id="back-top-inner"><div class="panel-pane pane-bmjj-back-to-top article-go-to-top" > <div class="pane-content"> <a href="#block-system-main" class="back-to-top" data-icon-position="" data-hide-link-title="0"><svg class="icon-article icon-arrow-up-top" aria-hidden="true"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="/sites/default/themes/bmjj/img/defs.svg#icon-arrow-up"></use></svg></a><a href="#article-bottom" class="back-to-top back-to-bottom" data-icon-position="" data-hide-link-title="0"><svg class="icon-article icon-arrow-up-top" aria-hidden="true"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="/sites/default/themes/bmjj/img/defs.svg#icon-arrow-down"></use></svg></a> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> <div class="panel-row-wrapper panel-row-last row" id="article-bottom-row"> <div class="bottom-wrapper col-narrow-12"> <div class="panel-panel panel-region-bottom"> <div class="inside"><div class="panel-pane pane-snippet pane-footer-marketing-slots" > <div class="pane-content"> <div class="snippet footer-marketing-slots" id="footer-marketing-slots"> <div class="snippet-content"> <iframe data-src="https://jobs.bmj.com/widget/bootstrap/job/#i=172" class="optanon-category-3" id="mdgxWidgetiFrame" title="careers widget"></iframe> <script type="text/javascript" src="//trendmd.s3.amazonaws.com/trendmd.min.js"></script> <script type="text/plain" class="optanon-category-4">TrendMD.register( {journal_id: 43066, element: '#trendmd-suggestions', track_id: null} );</script> <div id="trendmd-suggestions"></div> </div> </div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> </div> </div> </div><!-- /.region-content --> </div><!-- /.zone-content --> </div><!-- /.container --> </section> <!-- /.section-content --> </div> <!-- /.page --> <footer role="contentinfo" class="section section-footer container-fluid" id="footer"> <section role="contentinfo" class="section section-footer"> <div class="zone zone-footer footer-links"> <nav class="row"> <div class="region region-footerlinks1"> <div id="block-menu-block-1" class="block block-menu-block" class="block block-menu-block"> <div class="content"> <div class="menu-block-wrapper menu-block-1 menu-name-menu-footer-menu-1 parent-mlid-0 menu-level-1"> <ul class="menu"><li class="first expanded menu-mlid-15208 col-mobile-12 col-narrow-3 col-normal-3 col-wide-3"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Content</a><ul class="menu"><li class="first leaf menu-mlid-15209"><a href="/content/early/recent" class="" data-icon-position="" data-hide-link-title="0">Latest content</a></li> <li class="leaf menu-mlid-15210"><a href="/content/current" class="" data-icon-position="" data-hide-link-title="0">Current issue</a></li> <li class="leaf menu-mlid-15211"><a href="/content/by/year" class="" data-icon-position="" data-hide-link-title="0">Archive</a></li> <li class="leaf menu-mlid-15212"><a href="https://jnnp.bmj.com/pages/jnnp-100-a-centenary-of-publishing-neuroscience-achievement/" class="" data-icon-position="" data-hide-link-title="0">JNNP 100</a></li> <li class="leaf menu-mlid-15213"><a href="http://jnnp.bmj.com/pages/browse-by-topic/" class="" data-icon-position="" data-hide-link-title="0">Browse by collection</a></li> <li class="leaf menu-mlid-15214"><a href="http://jnnp.bmj.com/pages/most-read-articles/" class="" data-icon-position="" data-hide-link-title="0">Most read articles</a></li> <li class="leaf menu-mlid-15215"><a href="http://jnnp.bmj.com/pages/image-quiz/" class="" data-icon-position="" data-hide-link-title="0">Image quiz</a></li> <li class="last leaf menu-mlid-15216"><a href="http://jnnp.bmj.com/eletters" class="" data-icon-position="" data-hide-link-title="0">Responses</a></li> </ul></li> <li class="expanded menu-mlid-15217 col-mobile-12 col-narrow-3 col-normal-3 col-wide-3"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Journal</a><ul class="menu"><li class="first leaf menu-mlid-15218"><a href="http://jnnp.bmj.com/pages/about/" class="" data-icon-position="" data-hide-link-title="0">About</a></li> <li class="leaf menu-mlid-15219"><a href="http://jnnp.bmj.com/pages/editorial-board/" class="" data-icon-position="" data-hide-link-title="0">Editorial board</a></li> <li class="leaf menu-mlid-15220"><a href="https://myaccount.bmj.com/myaccount/signup.html?regService=etoc-alerts&corpusCode=jnnp&fwdUrl=https://jnnp.bmj.com/" class="" data-icon-position="" data-hide-link-title="0">Sign up for email alerts</a></li> <li class="leaf menu-mlid-15221"><a href="http://jnnp.bmj.com/pages/subscribe/" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Subscribe</a></li> <li class="last leaf menu-mlid-15222"><a href="http://jnnp.bmj.com/pages/thank-you-to-our-reviewers/" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Thank you to our reviewers</a></li> </ul></li> <li class="expanded menu-mlid-15223 col-mobile-12 col-narrow-3 col-normal-3 col-wide-3"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Authors</a><ul class="menu"><li class="first leaf menu-mlid-15224"><a href="http://jnnp.bmj.com/pages/authors/" class="" data-icon-position="" data-hide-link-title="0">Instructions for authors</a></li> <li class="leaf menu-mlid-15225"><a href="http://mc.manuscriptcentral.com/jnnp" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Submit an article</a></li> <li class="leaf menu-mlid-15226"><a href="http://authors.bmj.com/policies/" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Editorial policies</a></li> <li class="leaf menu-mlid-15227"><a href="http://openaccess.bmj.com/" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Open Access at BMJ</a></li> <li class="last leaf menu-mlid-15228"><a href="http://authors.bmj.com/" target="_blank" class="" data-icon-position="" data-hide-link-title="0">BMJ Author Hub</a></li> </ul></li> <li class="last expanded menu-mlid-15229 col-mobile-12 col-narrow-3 col-normal-3 col-wide-3"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Help</a><ul class="menu"><li class="first leaf menu-mlid-15230"><a href="http://jnnp.bmj.com/pages/contact-us/" class="" data-icon-position="" data-hide-link-title="0">Contact us</a></li> <li class="leaf menu-mlid-15231"><a href="http://journals.bmj.com/cgi/reprintform" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Reprints</a></li> <li class="leaf menu-mlid-15232"><a href="http://www.bmj.com/company/products-services/rights-and-licensing/permissions/" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Permissions</a></li> <li class="leaf menu-mlid-15233"><a href="http://www.bmj.com/company/contact-us/advertising-sponsorship/" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Advertising</a></li> <li class="last leaf menu-mlid-15234"><a href="http://myaccount.bmj.com/myaccount/customerservice/salesforce-form.html" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Feedback form</a></li> </ul></li> </ul></div> </div> </div> </div> </nav> <div class="row"> <nav class="col-mobile-12 col-narrow-3 col-normal-3 col-wide-3"> <div class="region region-footersocial"> <div id="block-panels-mini-social-icons" class="block block-panels-mini" class="block block-panels-mini"> <div class="content"> <div class="panel-display panel-1col clearfix" id="mini-panel-social_icons"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-bmjj-social-icons" > <div class="pane-content"> <ul class="menu"><li class="leaf"><a href="http://jnnp.bmj.com/pages/rss-feeds" class="link-icon-only link-icon"><span class="icon icon-rss"></span><span class="title element-invisible"> RSS</span></a></li><li class="leaf"><a href="http://twitter.com/JNNP_BMJ" class="link-icon-only link-icon"><span class="icon icon-twitter"></span><span class="title element-invisible"> Twitter</span></a></li><li class="leaf"><a href="http://www.facebook.com/JNNP.BMJ" class="link-icon-only link-icon"><span class="icon icon-facebook"></span><span class="title element-invisible"> Facebook</span></a></li><li class="leaf"><a href="http://blogs.bmj.com/jnnp/" class="link-icon-only link-icon"><span class="icon icon-blog"></span><span class="title element-invisible"> Blog</span></a></li><li class="leaf"><a href="https://soundcloud.com/bmjpodcasts/sets/jnnp" class="link-icon-only link-icon"><span class="icon icon-soundcloud"></span><span class="title element-invisible"> SoundCloud</span></a></li><li class="leaf"><a href="https://www.youtube.com/user/JNNPBMJ" class="link-icon-only link-icon"><span class="icon icon-youtube"></span><span class="title element-invisible"> YouTube</span></a></li></ul> </div> </div> </div> </div> </div> </div> </div> </div> </nav> </div> </div> </section><!-- /.section-footer --> <section class="row footer-platform"> <div class="col-mobile-12 col-narrow-4 logoBMJ"> <a href="http://www.bmj.com/company"><svg class="logo-bmj-svg" aria-hidden="true"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#logo-bmj"></use><svg></svg></svg></a> </div> <div class="col-mobile-12 col-narrow-8 legal"> <div class="legal-inner"> <ul> <li><a href="http://www.bmj.com/company/legal-information/">Website Terms & Conditions</a></li> <li><a href="http://www.bmj.com/company/your-privacy/">Privacy & Cookies</a></li> <li><a href="http://www.bmj.com/company/contact-us/">Contact BMJ</a></li> </ul> <!-- CookiePro Cookies Settings button start --> <button id="ot-sdk-btn" class="ot-sdk-show-settings">Cookie Settings</button> <!-- CookiePro Cookies Settings button end --> <p><small><span class="online-issn issn">Online ISSN: 1468-330X</span><span class="print-issn issn">Print ISSN: 0022-3050</span></small><br /> <small>Copyright © 2024 BMJ Publishing Group Ltd. All rights reserved. </small></p> </div> </div> </section> <div class="region region-absolute-bottom"> <div class="region-inner region-absolute-bottom-inner"> <div class="region region-absolute-bottom"> <div id="block-panels-mini-bottom-ad" class="block block-panels-mini text-center" class="block block-panels-mini text-center"> <div class="content"> <div class="panel-display one-layout " id="mini-panel-bottom_ad"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-dfp-pane" > <div class="pane-content"> <div id="dfp-ad-bottom-wrapper" class="dfp-tag-wrapper"> <div id="dfp-ad-bottom" class="dfp-tag-wrapper"> <script type="text/javascript"> googletag.cmd.push(function() { googletag.display("dfp-ad-bottom"); }); </script> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div><!-- /.region-absolute-bottom --> </footer><!-- /.section-footer --> <script type="text/javascript" src="/sites/default/files/advagg_js/js__xcXbPzItgCxLeD5Uy3L62U87U9ne3iv4g12sHKvzY80__MQ39WNLMHbEWS9SH5grYUB74j6iCxSoGMz9-a66u8_E__qw1DJnk-5gO1smAYQ6Cv-FvON600W_QtaIfAGcQ9MYA.js"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__Jd5dsvNznZMdglFu8sSni1wCsUfzvQbApHPAZwt5TY4__65Mqa1DMRwcSvPxjJEn6BXgMm-ckF3oOvkUTG9HRADI__qw1DJnk-5gO1smAYQ6Cv-FvON600W_QtaIfAGcQ9MYA.js" defer="defer"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__3YMnGGenZXx95e2d4w4qdZ8l2Nb4ScWnb6eRd_RG1Rk__bLDjtRazOW5NHwJqxd6XFtHApU0Yj0Keahi0hcnwqJ4__qw1DJnk-5gO1smAYQ6Cv-FvON600W_QtaIfAGcQ9MYA.js"></script> </body> </html>