@article{26bfe5543b4e408c8c48c1f0abb20964,
title = "Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study",
abstract = "This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66±1.47 vs -0.71±1.09, P=0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution(DSS) test, and a verbal fluency test (P<0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P<0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.",
keywords = "MCI, PET, alzheimer's disease, amyloid, cognitive decline, florbetapir",
author = "Doraiswamy, {P. Murali} and Sperling, {R. A.} and K. Johnson and Reiman, {Eric M.} and Wong, {T. Z.} and Sabbagh, {M. N.} and Sadowsky, {Carl H.} and Fleisher, {A. S.} and A. Carpenter and Joshi, {A. D.} and M. Lu and M. Grundman and Mintun, {M. A.} and Skovronsky, {D. M.} and Pontecorvo, {M. J.} and Ranjan Duara and Marwan Sabbagh and Ahern, {Geoffrey Lawrence} and Holub, {Richard F.} and Farmer, {Mildred V.} and Safirstein, {Beth Emmie} and Gustavo Alva and Longmire, {Crystal F.} and George Jewell and Johnson, {Keith A.} and Ron Korn and Wendt, {Jeanette K.} and Dean Wong and Coleman, {R. Edward} and Michael Devous and Danna Jennings and Weiner, {Michael W.} and Murphy, {Cynthia A.} and Kovnat, {Karel D.} and Williamson, {Jeff D.}",
note = "Funding Information: PMD 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 the University of California, National University of Singapore, University of Cambridge, Royal College of Psychiatrists, Radiologic Society of North America, Alzheimer{\textquoteright}s Association, Alzheimer{\textquoteright}s Foundation of America, Postgraduate Press, Avid/Lilly, Medivation, Bristol Myers, Accera, Piramal, Grifols, Baxter, Nutricia, Great Falls Living, Sonexa, Schering, TauRx, Baxter, Elan, Genomind, Shire, Neuroptix, Bayer, Neuronetrix, Otsuka, AstraZeneca, Envivo, Targacept, Abbvie, Neurocog Trials, Lundbeck and Edwards Hospital. He received publishing royalties from a book. He owns stock in Sonexa, Clarimedix, Maxwell Health and Adverse Events Inc, whose products are not discussed in this manuscript. RAS 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. KJ was a co-investigator in the trial and has consulted for GE Healthcare, Bayer-Schering, Pfizer, Elan/Janssen and Seimens. KJ has received research support from Avid/Lilly, Bristol-Myers-Squib, Janssen (JanssenAI) and Pfizer. EMR 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 Department of Health Services, AstraZeneca and Avid. TZW has served as a scientific advisor for Lilly and a site coinvestigator on Avid studies. MNS has served in a consulting or advisory capacity for Lilly, Amerisciences, Takeda, Eisai, Pfizer, 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. CHS has served on speaker bureaus for Novartis, Forest, Accera and as a consultant to Lilly. ASF has served as a consultant to Lilly and Avid, and received grant funding from Avid. AC, ADJ, ML, MAM, DMS and MJP are employees of Avid, a division of Eli Lilly, and except for ML, formerly held Avid stock or options. MG has served as a consultant to Acumen, Adamas, ALSP, Avid, Astra-Zeneca, Biogen Idec, Elan, Helicon, Intellect Neurosciences, Janssen Alzheimer Immunotherapy, J&J, Lilly, Medimmune, Neurophage, Neurogenetic Pharmaceuticals, Phloronol and Teva and on advisory boards for Helicon, Nutricia North America and Bristol Myers Squibb. MG owns stock in Prothena, and formerly held Avid stock options. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited All rights reserved.",
year = "2014",
month = sep,
day = "11",
doi = "10.1038/mp.2014.9",
language = "English (US)",
volume = "19",
pages = "1044--1051",
journal = "Molecular psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "9",
}