Abstract
INTRODUCTION: To support clinical trial designs focused on early interventions, our study determined reliable early amyloid-β (Aβ) accumulation based on Centiloids (CL) in pre-dementia populations. METHODS: A total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer's Disease–Prognostic and Natural History Study (AMYPAD-PNHS) and Insight46 who underwent [ 18F]flutemetamol, [ 18F]florbetaben or [ 18F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95 th percentile of longitudinal measurements in sub-populations (N PNHS = 101/750, N Insight46 = 35/382) expected to remain stable over time. The baseline CL threshold that optimally predicts future accumulation was investigated using precision-recall analyses. Accumulation rates were examined using linear mixed-effect models. RESULTS: Reliable accumulation in the PNHS was estimated to occur at >3.0 CL/year. Baseline CL of 16 [12,19] best predicted future Aβ-accumulators. Rates of amyloid accumulation were tracer-independent, lower for APOE ε4 non-carriers, and for subjects with higher levels of education. DISCUSSION: Our results support a 12–20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations.
Original language | English |
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Pages (from-to) | 3429-3441 |
Number of pages | 13 |
Journal | Alzheimer's & Dementia |
Volume | 20 |
Issue number | 5 |
Early online date | 1 Apr 2024 |
DOIs | |
Publication status | Published - May 2024 |
Keywords
- Alzheimer's
- amyloid
- Centiloid
- longitudinal PET
- quantification
- reliable accumulation
- WHITE-MATTER REFERENCE
- ALZHEIMERS-DISEASE
- IMAGING BIOMARKER
- COGNITIVE DECLINE
- BETA DEPOSITION
- PET
- THRESHOLD
- SCALE