Concordance between Centiloid quantification and visual interpretation of amyloid PET scans across the Alzheimer's disease continuum.

Mohammad Khalafi, Seyed Hani Hojjati, Xiuyuan H Wang, Liangdong Zhou, Anna S Nordvig, Yi Li, Tracy A Butler, Qolamreza R Razlighi, Emily B Tanzi, Silky Pahlajani, Lidia Glodzik, Nancy S Foldi, Mony J de Leon, Gloria C Chiang
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Abstract

Background and purpose: Accurate identification of cerebral beta-amyloid (Aβ) accumulation is crucial for diagnosing Alzheimer's disease (AD) and determining eligibility for anti-Aβ therapies. The Centiloid (CL) scale has emerged as a standardized method to harmonize Aβ positron emission tomography (PET) quantification across different tracers and sites. We aimed to evaluate the concordance between CL quantification and visual interpretation in a cohort of cognitively impaired (CI) and unimpaired (CU) participants who underwent Aβ PET.

Materials and methods: Two hundred twenty-one participants (mean age 69 ± 12.3 years) were prospectively enrolled in AD studies and underwent 247 Aβ PET scans, including 157 with [11C]Pittsburgh Compound B (PiB) and 90 with [18F]Florbetaben (FBB). Standardized uptake value ratios (SUVRs) were converted to the CL scale following Global Alzheimer's Association Interactive Network (GAAIN) guidelines. Percent agreement and kappa statistics were used to evaluate the concordance between CL thresholds and visual interpretation in determining Aβ positivity.

Results: The highest concordance rate for the whole cohort was 93% using a CL cutoff of 18 (kappa coefficient 0.84). Using FBB, the concordance rate was highest using a CL cutoff of 24 (97%), whereas the concordance rate for PiB peaked at 94% at a CL cutoff of 18. Concordance was higher in negative than positive Aβ PET cases, 98% versus 90%. Concordance was slightly higher in CI participants, compared to CU (96% versus 93%). Disagreement commonly occurred when focal areas of Aβ positivity were identified on visual interpretation but did not meet the threshold globally by CL quantification.

Conclusions: Global CL quantification of Aβ PET scans is highly concordant with visual interpretation. Combining both methods may provide a more complete assessment of the extent of Aβ deposition in the brain.

Abbreviations: AD = Alzheimer's disease; Aβ = beta-amyloid; PET = positron emission tomography; PiB = Pittsburgh Compound B; FBB = Florbetaben; CL = Centiloid.

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