Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease.
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.
Fleisher, AS; Chen, K; Liu, X; Roontiva, A; Thiyyagura, P; Ayutyanont, N; Joshi, AD; Clark, CM; Mintun, MA; Pontecorvo, MJ; Doraiswamy, PM; Johnson, KA; Skovronsky, DM; Reiman, EM
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