Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study

Authors

P. Murali Doraiswamy, Duke University Medical Center
R. A. Sperling, Massachusetts General Hospital
K. Johnson, Massachusetts General Hospital
K. Johnson, Massachusetts General Hospital
Eric M. Reiman, Banner Alzheimer's Institute
T. Z. Wong, Duke University Medical Center
M. N. Sabbagh, Banner Sun Health Research InstituteFollow
Carl H. Sadowsky, Nova Southeastern University
A. S. Fleisher, Banner Alzheimer's Institute
A. Carpenter, Avid Radiopharmaceuticals, Inc
A. D. Joshi, Avid Radiopharmaceuticals, Inc
M. Lu, Avid Radiopharmaceuticals, Inc
M. Grundman, University of California, San Diego
M. A. Mintun, Avid Radiopharmaceuticals, Inc
D. M. Skovronsky, Avid Radiopharmaceuticals, Inc
M. J. Pontecorvo, Avid Radiopharmaceuticals, Inc
Ranjan Duara, The Mount Sinai Medical Center
Marwan Sabbagh, Banner Sun Health Research InstituteFollow
Geoffrey Lawrence Ahern, The University of Arizona Health Sciences
Richard F. Holub, Neurological Associates of Albany
Mildred V. Farmer, Meridien Research
Beth Emmie Safirstein, MD Clinical
Gustavo Alva, ATP Clinical Research
Crystal F. Longmire, Medical University of South Carolina
George Jewell, Dayton Center for Neurological Disorders
Ron Korn, Scottsdale Medical Imaging
Jeanette K. Wendt, Northwest Neurospecialists
Dean Wong, Johns Hopkins Medical Institutions
R. Edward Coleman, Duke University Medical CenterFollow
Michael Devous, UT Southwestern Medical Center
Danna Jennings, Molecular Neuroimaging
Michael W. Weiner, VA Medical Center

Document Type

Article

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.

Publication Date

9-11-2014

Publication Title

Molecular Psychiatry

ISSN

13594184

E-ISSN

14765578

Volume

19

Issue

9

First Page

1044

Last Page

1051

PubMed ID

24614494

Digital Object Identifier (DOI)

10.1038/mp.2014.9

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