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
Authors: Rosita Shishegar, Vincent Doré, Pierrick Bourgeat, James D. Doecke, Rodrigo Cánovas, Simon M. Laws, Tenielle Porter, Michael Weiner, Colin L. Masters, Hamid R. Sohrabi, Jurgen Fripp, Paul Maruff, Victor L. Villemagne, Christopher C. Rowe, for the Alzheimer's Disease Neuroimaging Initiativethe Australian Imaging BiomarkersLifestyle flagship study of ageing
Institutions: Commonwealth Scientific and Industrial Research Organisation, Australian e-Health Research Centre, RMIT University, Edith Cowan University, University of California, San Francisco, University of California San Francisco Medical Center, The University of Western Australia, Murdoch University, University of Pittsburgh, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Austin Health
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Funders: U.S. Department of Defense, Alzheimer's Association, Larry L. Hillblom Foundation, California Department of Public Health, Biogen, Northern California Institute for Research and Education, Australian Government, Commonwealth Scientific and Industrial Research Organisation, Australian Catholic University, National Institutes of Health, University of California, San Francisco, National Health and Medical Research Council, National Institute on Aging, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W7225411554