4.0 Article

Using Positron Emission Tomography and Florbetapir F 18 to Image Cortical Amyloid in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer Disease

Journal

ARCHIVES OF NEUROLOGY
Volume 68, Issue 11, Pages 1404-1411

Publisher

AMER MEDICAL ASSOC
DOI: 10.1001/archneurol.2011.150

Keywords

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Funding

  1. Avid Radiopharmaceuticals
  2. Eli Lilly
  3. Avid
  4. Lundbeck
  5. Medivation
  6. TauRx
  7. Bayer
  8. GE Healthcare
  9. BMS
  10. Astra
  11. Shering
  12. Neuroptix
  13. Neuronetrix
  14. Alzheimer's Foundation
  15. Sonexa
  16. Janssen Alzheimer Immunotherapy

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Objectives: To characterize quantitative florbetapir F 18 (hereafter referred to as simply florbetapir) positron emission tomographic (PET) measurements of fibrillar beta-amyloid (A beta) burden in a large clinical cohort of participants with probable Alzheimer disease (AD) or mild cognitive impairment (MCI) and older healthy controls (OHCs). Design: Cerebral-to-whole-cerebellar florbetapir standard uptake value ratios (SUVRs) were computed. Mean cortical SUVRs were compared. A threshold of SUVRs greater than or equal to 1.17 was used to reflect pathological levels of amyloid associated with AD based on separate antemortem PET and postmortem neuropathology data from 19 end-of-life patients. Similarly, a threshold of SUVRs greater than 1.08 was used to signify the presence of any identifiable A beta because this was the upper limit from a separate set of 46 individuals 18 to 40 years of age who did not carry apolipoprotein E (APOE) epsilon 4. Setting: Multiple research imaging centers. Participants: A total of 68 participants with probable AD, 60 participants with MCI, and 82 OHCs who were 55 years of age or older. Main Outcome Measure: Florbetapir-PET activity. Results: All of the participants (ie, those with probable AD or MCI and those who were OHCs) differed significantly in mean (SD) cortical florbetapir SUVRs (1.39 [0.24], 1.17 [0.27], and 1.05 [0.16], respectively; P < 1.0 X 10(-7)), in percentage meeting levels of amyloid associated with AD by SUVR criteria (80.9%, 40.0%, and 20.7%, respectively; P < 1.0 X 10(-7)), and in percentage meeting SUVR criteria for the presence of any identifiable A beta (85.3%, 46.6%, and 28.1%, respectively; P < 1.0 X 10(-7)). Among OHCs, the percentage of florbetapir positivity increased linearly by age decile (P =. 05). For the 54 OHCs with available APOE genotypes, APOE e4 carriers had a higher mean (SD) cortical SUVR than did noncarriers (1.14 [0.2] vs 1.03 [0.16]; P =. 048). Conclusions: The findings of our analysis confirm the ability of florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI, and OHC groups using continuous and binary measures of fibrillar A beta burden. It introduces criteria to determine whether an image is associated with an intermediate-to-high likelihood of pathologic AD or with having any identifiable cortical amyloid level above that seen in low-risk young controls.

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