ment of Alzheimer disease (AD) are hampered by the lack of noninvasive biomarkers of the underlying pathology. Between 10% and 20% of patients clinically diagnosed with AD lack AD pathology at autopsy, 1-3 and community physicians may not diagnose AD in 33% of patients with mild signs and symptoms. 4 Thus, a diagnostic biomarker may help clinicians separate patients who have AD pathology from those who do not. See also pp 261 and 304.

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The objectives of this study were to examine the effective dose range and the test-retest reliability of florbetapir F 18 using, first, visual assessment by independent raters masked to clinical information and, second, semiautomated quantitative measures of cortical target area to cerebellum standardized uptake value ratios (SUVr) as primary outcome measures. Visual ratings of PET image quality and tracer retention or b-amyloid (Ab) binding expressed as SUVrs were compared after intravenous administration of either 111 MBq (3 mCi) or 370 MBq (10 mCi) of florbetapir F 18 in patients with Alzheimer's disease (AD) (n 5 9) and younger healthy controls (YHCs) (n 5 11). In a separate set of subjects (AD, n 5 10; YHCs, n 5 10), test-retest reliability was evaluated by comparing intrasubject visual read ratings and SUVrs for 2 PET images acquired within 4 wk of each other. Results: There were no meaningful differences between the 111-MBq (3-mCi) and 370-MBq (10-mCi) dose in the visual rating or SUVr. The difference in the visual quality across 111 and 370 MBq showed a trend toward lower image quality, but no statistical significance was achieved (t test; t 1 5 21.617, P 5 0.12) in this relatively small sample of subjects. At both dose levels, visual ratings of amyloid burden identified 100% of AD subjects as Ab-positive and 100% of YHCs as Ab-negative. Mean intrasubject test-retest variability for cortical average SUVrs with the cerebellum as a reference over the 50-to 70-min period was 2.4% 6 1.41% for AD subjects and 1.5% 6 0.84% for controls. The overall SUVr test-retest correlation coefficient was 0.99. The overall k-statistic for test-retest agreement for Ab classification of the masked reads was 0.89 (95% confidence interval, 0.69-1.0). Conclusion: Florbetapir F 18 appears to have a wide effective dose range and a high testretest reliability for both quantitative (SUVr) values and visual assessment of the ligand. These imaging performance properties provide important technical information on the use of florbetapir F 18 and PET to detect cerebral amyloid aggregates.

Objective To evaluate the performance characteristics of florbetapir F 18 PET in patients with Alzheimer’s disease dementia (AD), mild cognitive impairment (MCI) and healthy control subjects (HC). Methods Florbetapir PET was acquired in 184 subjects (45 AD, 60 MCI, and 79 HC) within a multi-center phase 2 study. Amyloid burden was assessed visually and quantitatively and classified as positive or negative. Results Florbetapir PET was visually rated amyloid positive in 76% of AD, 38% of MCI and 14% of HC. 84% of AD, 42% of MCI, and 23% of HC were classified as amyloid positive using a quantitative threshold. Amyloid positivity and mean cortical amyloid burden were associated with age and APOE ε4 carrier status. Interpretation The data are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI, and indicate potential value of florbetapir F 18 PET as an adjunct to clinical diagnosis.

Objectives: Florbetapir F 18 PET can image amyloid-␤ (A␤) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting A␤ pathology using florbetapir PET in subjects at risk for progressive cognitive decline. Methods:A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (A␤ϩ) or negative (A␤Ϫ) for pathologic levels of ␤-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.