Work

Optimized amyloid‐β PET centiloid and cognitive cutoffs predict progression from mild cognitive impairment to Alzheimer's dementia

Year: 2026

Type: article

Abstract: INTRODUCTION: This study aimed to develop optimized prognostic cutoffs for amyloid-β-positron emission tomography (Aβ-PET) and Mini-Mental State Examination (MMSE) that predict 3-year progression from Clinical Dementia Rating Global (CDR-Global) score 0.5 to 1.0 in mild cognitive impairment (MCI) participants and validate against cognitive decline/functional trajectories. METHODS: We analyzed 454 CDR-global = 0.5 Aβ-positive (> 25 Centiloid [CL]) MCI participants from Australian Imaging Biomarkers and Lifestyle (AIBL) (N = 99) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 355), followed up to seven years. Youden index derived optimal Aβ-PET and MMSE thresholds for 3-year progression. Participants were stratified into four groups by combined Aβ-PET/MMSE status. Adjusted Cox models (age, sex, education, apolipoprotein E [APOE] ε4) assessed progression to CDR-Global score of 1.0 Alzheimer's disease (AD) dementia (confirmed with Aβ-PET); adjusted linear mixed models assessed CDR Sum of Boxes (CDR-SoB) and Preclinical Alzheimer's Cognitive Composite (PACC) trajectories. RESULTS: Optimal cutoffs were Aβ-PET > 71 CL (hazard ratio [HR] = 2.67; 3-year risk = 36.7%) and MMSE score of < 27 (HR = 2.27; 36.8%). The combined high Aβ/low MMSE group showed a 6.39-fold risk and 47.8% 3-year progression, with the steepest decline. DISCUSSION: Prognostically optimized Aβ-PET and MMSE cutoffs improve 3-year risk stratification beyond common diagnostic thresholds, supporting dual-cutoff prognostic enrichment.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.71892