Clinical and Biologic Characterization of a 3-Level Centiloid-Based Classification of Amyloid PET

Area of Science:

• Neurology
• Biomarker Research
• Neuroimaging

Background:

• Amyloid PET interpretation often relies on binary classification, potentially missing nuanced disease stages.
• Quantitative Centiloid analysis identifies an intermediate amyloid burden range with unclear clinical significance.
• This intermediate category has implications for understanding disease progression and treatment eligibility.

Purpose of the Study:

• To characterize the intermediate Centiloid range using multimodal biomarkers and longitudinal cognitive data.
• To establish Centiloid thresholds for early tau PET positivity, advanced tau PET positivity, and cognitive decline.
• To evaluate the clinical relevance of a three-level amyloid PET interpretation.

Main Methods:

• Retrospective analysis of 512 participants undergoing amyloid PET (2016-2024).
• Quantification of global amyloid burden in Centiloids, categorizing participants into low (<12), intermediate (12-37), and high (>37) groups.
• Assessment of fluid biomarkers, tau PET, and cognitive changes (MMSE) using statistical analyses.

Main Results:

• The intermediate group (12% of participants) exhibited biomarker profiles between low and high amyloid groups.
• Both intermediate and high Centiloid groups showed faster cognitive decline compared to the low group.
• Established Centiloid thresholds: 13 for cognitive decline, 14 for mesial temporal tau, and 51 for advanced neocortical tau.

Conclusions:

• Centiloid classification defines distinct biological and clinical stages of amyloid pathology.
• Intermediate amyloid burden is associated with early tau involvement and elevated cognitive decline risk.
• A three-level interpretation of amyloid PET is biologically and clinically meaningful, highlighting the intermediate zone's importance.