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Original Contributions |

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

Adam S. Fleisher, MD; Kewei Chen, PhD; Xiaofen Liu, MS; Auttawut Roontiva, MS; Pradeep Thiyyagura, MS; Napatkamon Ayutyanont, PhD; Abhinay D. Joshi, MS; Christopher M. Clark, MD; Mark A. Mintun, MD; Michael J. Pontecorvo, PhD; P. Murali Doraiswamy, MBBS, FRCP; Keith A. Johnson, MD; Daniel M. Skovronsky, MD, PhD; Eric M. Reiman, MD
Arch Neurol. 2011;68(11):1404-1411. doi:10.1001/archneurol.2011.150.
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Objectives To characterize quantitative florbetapir F 18 (hereafter referred to as simply florbetapir) positron emission tomographic (PET) measurements of fibrillar β-amyloid (Aβ) 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 Aβ 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) ε4.

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 × 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 × 10−7), and in percentage meeting SUVR criteria for the presence of any identifiable Aβ (85.3%, 46.6%, and 28.1%, respectively; P < 1.0 × 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 ε4 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 Aβ 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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Figures

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Figure 1. Cortical region of interest template, which includes the orbital frontal cingulate (A), the temporal cingulate (B), the anterior cingulate (C), the posterior cingulate (D), the parietal lobe (E), and the precuneus (F).

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Figure 2. Scatterplots of mean cortical standard uptake value ratios (SUVRs) for persons having florbetapir F 18 levels associated with intermediate or high likelihood neuropathological Alzheimer disease (AD) (hereafter referred to as the PATHAMY levels) and young adult APOE ε4 noncarriers (YNC), and for the following clinical diagnostic groups: probable AD (PAD), mild cognitive impairment (MCI), and older healthy control (OHC) group. The black line represents a florbetapir threshold associated with minimal SUVRs seen in the PATHAMY group (≥1.17). The red line represents the minimal SUVR associated with the presence of any identifiable Aβ (hereafter referred to as the any-amyloid levels; >1.08). Mean cortical SUVRs differed significantly among diagnostic groups (P = 2.9 × 10−14).

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Figure 3. Mean between-group differences in cerebral-to-cerebellar florbetapir standard uptake value ratios (SUVRs). Representative horizontal, coronal, and sagittal sections show mean between-group increases. The images are displayed as mean differences (P ≤ .05). Typical patterns of amyloid distribution in Alzheimer disease (AD) are demonstrated with preferential uptake in the parietal, frontal, and temporal lobes. MCI indicates mild cognitive impairment group of patients; OHC, older healthy control group; PAD, probable AD group.

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Figure 4. Percentages of florbetapir positivity by diagnostic group. The percentages of positivity in all 3 diagnostic groups and in 2 subgroups of older healthy controls (APOE ε4 carriers [OHC E4+] and noncarriers [OHC E4−]) are based on meeting criteria for florbetapir F 18 levels associated with intermediate or high likelihood neuropathological Alzheimer disease (AD) (hereafter referred to as PATHAMY levels, with a standard uptake value ratio [SUVR] of ≥1.17) or the presence of any identifiable cortical Aβ (hereafter referred to as any-amyloid levels, with SUVR > 1.08). The probable AD (PAD), mild cognitive impairment (MCI), and OHC diagnostic groups differed significantly in their percentage of positivity for both thresholds (P < 1.0 × 10−7) but not between the 2 OHC subgroups, likely owing to the small sample size. Only the full OHC group shows significant differences in their percentage of positivity based on threshold used (P = .03).

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Figure 5. Percentages of florbetapir positivity by age in older healthy controls (OHCs). The percentages increased by age decile in OHCs (P = .05 for pathological amyloid threshold and P = .01 for presence of any identifiable cortical Aβ). SUVR indicates standard uptake value ratio.

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