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

P. Murali Doraiswamy, R. A. Sperling, K. Johnson, Eric M. Reiman, T. Z. Wong, M. N. Sabbagh, Carl H. Sadowsky, A. S. Fleisher, A. Carpenter, A. D. Joshi, M. Lu, M. Grundman, M. A. Mintun, D. M. Skovronsky, M. J. Pontecorvo, Ranjan Duara, Marwan Sabbagh, Geoffrey Lawrence Ahern, Richard F. Holub, Mildred V. FarmerBeth Emmie Safirstein, Gustavo Alva, Crystal F. Longmire, George Jewell, Keith A. Johnson, Ron Korn, Jeanette K. Wendt, Dean Wong, R. Edward Coleman, Michael Devous, Danna Jennings, Michael W. Weiner, Cynthia A. Murphy, Karel D. Kovnat, Jeff D. Williamson

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1044-1051
Number of pages8
JournalMolecular psychiatry
Volume19
Issue number9
DOIs
StatePublished - Sep 11 2014

Keywords

  • MCI
  • PET
  • alzheimer's disease
  • amyloid
  • cognitive decline
  • florbetapir

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Molecular Biology

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