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Abstract

Objectives:

Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.

Methods:

A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ−) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.

Results:

In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating–sum of boxes (CDR-SB) (p < 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ− subjects (p < 0.10).

Conclusions:

Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.

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Supplementary Material

File (appendix_e-1.docx)
File (coinvestigators.docx)
File (figure_e-1.docx)
File (table_e-1.docx)
File (table_e-2.docx)
File (znl04012001628.pdf)

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Information & Authors

Information

Published In

Neurology®
Volume 79Number 16October 16, 2012
Pages: 1636-1644
PubMed: 22786606

Publication History

Received: December 22, 2011
Accepted: May 1, 2012
Published online: July 11, 2012
Published in print: October 16, 2012

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Disclosure

P.M. Doraiswamy has received research grants through Duke University from NIA, NIMH, NINDS, NHLBI, University of California (ADCS), Northern California Research Institute (ADNI), Avid/Lilly, Elan, Bristol-Myers, Ono, Sanofi, Novartis, Medivation, and Neuronetrix in the recent past. He has received advisory or speaking fees from Avid/Lilly, Medivation, BristolMyers, Accera, Sonexa, Schering, TauRx, Baxter, Neuroptix, Bayer, Neuronetrix, Otsuka, AstraZeneca, Lundbeck, and Edwards Hospital. He owns stock in Sonexa, Clarimedix, and Adverse Events Inc, whose products are not discussed in this manuscript. R.A. Sperling has served as a site investigator for Avid, BMS, Elan, Janssen, Pfizer, and Wyeth and as a consultant to Bayer, BMS, Elan, Eisai, Janssen, Pfizer, Roche, and Wyeth, and as an unpaid consultant to Avid. She has received speaking honoraria from Prizer, Janssen, Eli Lilly, and Bayer. R.E. Coleman was a site PI for the clinical study and served on an advisory board to Avid and Lilly. K.A. Johnson was a co-investigator in the trial and has consulted for GE Healthcare, Bayer-Schering, Pfizer, Elan/Janssen, and Seimens. He has received research support from Avid/Lilly, Bristol-Myers-Squib, Janssen (JanssenAI), and Pfizer. E.M. Reiman has served as a scientific advisor to Sygnis, AstraZeneca, Bayer, Eisai, Elan, Eli Lilly, GlaxoSmithKline, Intellect, Link Medicine, Novartis, Siemens, and Takeda. He has had research contracts with NIA the Arizona Dept. of Health Services, AstraZeneca, and Avid. M.D. Davis has received training support from NIDDK grant 2T32DK060455, is an employee at Theorem Clinical Research, and performed statistical analyses under a contract from Avid. M. Grundman has served as a consultant to Acumen, Adamas, ALSP, Avid, Biogen Idec, Elan, Helicon, Intellect Neurosciences, Janssen Alzheimer Immunotherapy, J&J, Lilly, Neurophage, and Teva and on advisory boards for Helicon, Nutricia North America, and Bristol Myers Squibb. He owns stock in Elan and formerly held Avid stock options. M.N. Sabbagh has served in a consulting or advisory capacity for Lilly, Amerisciences, Takeda, Eisai, Pfizer, and GSK and has received royalties from Wiley and Amerisciences. He has received contracts and grants from Celgene, Ceregene, Bayer, Baxter, BMS, Lilly, Pfizer, Wyeth, Janssen, Elan, Avid, Genentech, and Eisai. C.H. Sadowsky has served on speaker bureaus for Novartis, Forest, and Accera and as a consultant to Lilly. A.S. Fleisher has served as a consultant to Lilly and Avid and received grant funding from Avid. A. Carpenter is an employee of Avid, a division of Eli Lilly, and formerly held Avid stock or options. C.M. Clark, deceased, was an employee at Avid; disclosures are not included for this author. A.D. Joshi, M.A. Mintun, D.M. Skovronsky, and M.J. Pontecorvo are employees of Avid, a division of Eli Lilly, and formerly held Avid stock or options. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

P. Murali Doraiswamy, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
1) Avid/Lilly, 2)Medivation, 3) BristolMyers, 4) Accera, 5) Sonexa, 6) Schering, 7) TauRx, 8) Baxter, 9)Neuroptix, 10) Bayer, 11) Neuronetrix
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1) Accera, 2) Lundbeck, 3) AstraZeneca, 4) Edwards Hospital, 5) University California, 6) National University of Singapore
Editorial Boards:
1.
Pharmacotherapy (editorial board member)
Patents:
1.
NONE
Publishing Royalties:
1.
The Alzheimer’s Action Plan, 2008, St Martins Press
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
1) Rutgers University, 2) NIH
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Research grants to Duke university from 1) Avid, 2) Elan, 3) Lilly, 4) BristolMyers, 5)Ono, 6) Sanofi, 7) Novartis, 8) Medivation, 9) Neuronetrix
Research Support, Government Entities:
1.
1) NIA, 2) NIMH, 3) NINDS, 4)NHLBI
Research Support, Academic Entities:
1.
1) University of California - ADCS, 2) Northern California Research Institute - ADNI
Research Support, Foundations and Societies:
1.
Alzheimer Drug Discovery Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
1) Sonexa, 2) Clarimedix, 3)AdverseEvents Inc
Legal Proceedings:
1.
NONE
Reisa A. Sperling, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Pfizer - AD/PD symposium speaker honorarium
Editorial Boards:
1.
Alzheimer’s Disease and Associated Disorders 2007-2010
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
has served as a consultant for Roche, Janssen, Pfizer Inc, Bayer Schering Pharma, Eisai Inc., Satori, Kyowa Hakko Kirin, Bristol-Myers Squibb and Avid Radiopharmaceuticals, (unpaid);
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Janssen, clinical trial investigator 2008-2009,Bristol- Myers-Squibb, clinical trial investigator 2009-2010
Research Support, Government Entities:
1.
1) National Institute on Aging R01AG027435, principal investigator, 2006-2012; 2) National Institute on Aging P01AG036694, principal investigator, 2010-2015. 3) National Institute on Aging P50 AG005134, 2008-2013; Project leader.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Alzheimer’s Association, principal investigator, 2007-2009 Anonymous Foundation, principal investigator, 2009-2010 American Health Assistance Foundation, principal investigator, 2010.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
R. Edward Coleman, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Deceased.
Disclosure
Scientific Advisory Boards:
1.
Medical advisory board--Avid Radiopharmaceuticals, Inc; and Lilly(2011,2012); Bayer; Speakers’ Bureaus: Lilly;
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
Department of Radiology, Duke University Medical Center,Amyloid imaging study,<5%
Research Support, Commercial Entities:
1.
Clinical Trial, Avid Radiopharmaceuticals Inc. (2011,2012)
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Keith A. Johnson, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Pfizer Inc., travel and speaker honoraria
Editorial Boards:
1.
Journal of Neuroimaging, Associate Editor, 2005-2012
Patents:
1.
NONE
Publishing Royalties:
1.
The Whole Brain Atlas, Williams and Wilkins, 1999
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
1) GEHC Ltd; 2) Avid/Lilly ; 3) Bayer-Schering; 4) Pfizer; 5) Elan/Janssen; 6) Bristol-Myers-Squib
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
1) Division of Nuclear Medicine and Molecular Imaging, Department of Imaging, Massachusetts General Hospital, Boston, MA., <5%, 2002-2011; 2) Memory Disorders Unit, Department of Neurology, Brigham and Women’s Hospital, Boston, MA., <5%, 1993-2011.
Research Support, Commercial Entities:
1.
1) Avid/Lilly; 2) Bristol-Myers-Squib; 3) Janssen (JanssenAI); 4) Pfizer
Research Support, Government Entities:
1.
1) NIH/NIA R01 AG037497, principal investigator, 2010- 2011; NIH/NIA: R01 AG027435S, co-princpal investigator, 2005- 2011; P50 AG00513421, co-investigator, 2002-2011; P01 AG036694 co-principal investigator, 2009-2011; R01 AG021910, co-investigator, 2008-2011; K23 AG033634, sponsor/mentor, 2009-2011; NIH/NINDS R01 NS062028, co- investigator, 2008-2011; NIH/NINDS R01 AG026484, co- investigator, 2010-2011; NIH/NIA R21 AG038994, co- investigator, 2011
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Alzheimer Association ZEN-10-174210, principal investigator, 2010-2011; Alzheimer Association IIRG-08-90934, co- investigator, 2008-2011; American Health Assistance Foundation, co-investigator, 2010-2011
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Eric M. Reiman, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
Accera Bayer Elan Eli Lilly AstraZeneca GlaxoSmithKline Siemens Takeda Eisai
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Deputy Editor, Journal of Clinical Psychiatry
Patents:
1.
Patent held: “Methods for Tracking the Progression of Alzheimer’s Disease Identifying Treatment Using Transgenic Mice
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Kronos Life Sciences GlaxoSmithKline AstraZeneca Avid
Research Support, Government Entities:
1.
NIA (R01 AG031581, PI) NIA (P30 AG19610, PI) State of Arizona (Arizona Alzheimer’s Consortium, PI)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Banner Alzheimer’s Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Mat D. Davis, MS
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Theorem Clinical Research, Statistician
Consultancies:
1.
Performed statistical consulting for Avid Radiopharmaceuticals
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), Grant Number 2T32DK060455, Statistician, 2010-2011
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Michael Grundman, MD, MPH
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
Helicon, Nutricia North America, Bristol Myers Squibb
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Acumen, Adamas, ALSP, Avid, Biogen Idec, Elan, Helicon, Intellect, Janssen Alzheimer Immunotherapy, Johnson& Johnson, Lilly, Neurophage, Teva
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
Elan, Avid
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Marwan N. Sabbagh, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
Amerisciences. I am chair of the SAB. It is a nutracuetical company. I am chair of the DSMB for Allon Pharmaceuticals. Chair the DSMB for Allan Pharmaceuticals PSP RCT
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
CLincal Neurology News, and Journal of Alzheimer’s Disease, BMC Neurology
Patents:
1.
NONE
Publishing Royalties:
1.
From the published book
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Advisory boards for GSK, Pfizer, BMS, Eisai, Amerisciences, Avid, Lilly, Takeda
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Support from Elan, Wyeth, Medivation, Avid, Baxter, Lilly, GE, Eisai, Bayer, Pfizer, BMS
Research Support, Government Entities:
1.
The NIA from the ADCC P30 and NIH RO1
Research Support, Academic Entities:
1.
The Alzheimer’s disease cooperative study, ADNI
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
Amerisciences pays royalties on the commercial product Cognivite
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Carl H. Sadowsky, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
1)Commercial: advisory board for Lilly 2)Commercial: advisory board for Novartis 3)Commercial: advisory board for Accera
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1)Commercial: Lilly 2)Commercial: Avid 3)Commercial: Novartis 4)Commercial: Accera 5)Commercial: Forrest Speakers’ Bureaus: 1)Commercial: Lilly 2)Commercial: Avid 3)Commercial: Novartis 4)Commercial: Accera 5)Commercial: Forrest
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Adam S. Fleisher, MD, MAS
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NIH funded grant for the study of omega 3 fatty acids in AD, DSMB Chair. SAB Eli-Lilly, Semagacestat SAB Elan,Scilo-inositol
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Employed by The Banner Alzheimer’s Institute, Non-profit
Consultancies:
1.
Dr. Fleisher has served as a consultant for Elan, Pfizer, Janssen and Wyeth Pharmaceuticals.
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Investigator initiated grant - Avid radiopharma, a whole- owned subsidiary of Eli-Lilly
Research Support, Government Entities:
1.
CO-INVESTIGATOR: NIA R01 AG031581 2008-2013 CO-INVESTIGATOR: NIA RC2 AG036535 2009-2011 PI NIA 1 K23 AG024062 2004-2009 Consultant NIA 5 U01 AG10483 2007-2012
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alan Carpenter, PhD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Avid Radiopharmaceuticals, Inc., Vice President, Regulatory Affairs
Consultancies:
1.
Avid Radiopharmaceuticals, Inc.
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Employment at Avid Radiopharmaceuticals, Inc.
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
Avid Radiopharmaceuticals, Inc.
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Christopher M. Clark, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Deceased.
Abhinay D. Joshi, MS
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Avid Radiopharmaceuticals Inc.
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Mark A. Mintun, MD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Avid Radiopharmaceuticals, Inc., Chief Medical Officer
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
Stock options in 2010 from Avid Radiopharmaceuticals
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Daniel M. Skovronsky, MD, PhD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Eisai: honorarium for speaking at 50th Annual Japanese Society of Nuclear Medicine Meeting 2010. Eisai: reimbursement of travel to 50th Annual Japanese Society of Nuclear Medicine Meeting 2010.
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Avid Radiopharmaceuticals, Inc. a wholly-owned subsidiary of Eli Lilly & Company - Chief Executive Officer
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
Avid Radiopharmaceuticals, Inc. - Stock and Stock Options 2010
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Michael J. Pontecorvo, PhD
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Avid Radiopharmaceuticals, a wholely owned swubsidiary of Eli Lilly Inc., Vice President Clinical Development
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
Avid Radiopharmaceuticals: Stock Options 2010
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
For the AV45-A11 Study Group
From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.

Notes

Coinvestigators are listed on the Neurology® Web site at www.neurology.org.
Correspondence & reprint requests to Dr. Doraiswamy: [email protected]; Dr. Pontecorvo: [email protected]

Author Contributions

P.M.D. served as the primary author of the manuscript, advised on study design, assisted with data collection, drafted the initial version of the manuscript, and was involved in data interpretation and critical revisions. R.A.S. contributed to data collection and manuscript revisions. R.E.C. contributed to subject recruitment and participated in manuscript writing. K.A.J. collected data and revised the manuscript. E.M.R. contributed to the study design, interpretation of the findings, and reviewing the manuscript. M.D.D. performed the statistical analyses. M.G. contributed to the data analysis, interpretation, and manuscript revisions. M.N.S. contributed to data collection, manuscript review, and study design. C.H.S. contributed to data collection and reviewing the manuscript. A.F. contributed to data collection and editing the manuscript. A.C. contributed to study design, data review, and interpretation. C.M.C. contributed to study design and data interpretation. A.D.J. contributed to study design, reviewing the literature, drafting figures, and drafting the manuscript. M.A.M. contributed to administrative support, funding, data analysis, and manuscript review. D.M.S. contributed to study design, data review, and manuscript writing. M.J.P. contributed to study design, conduct, data analysis and interpretation, and review of the manuscript.

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