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Peer-reviewedCC BY 4.0Alzheimer's & Dementia

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

  • Rosita Shishegar1,2
  • Vincent Doré1
  • Pierrick Bourgeat3
  • James D. Doecke3,4
  • Rodrigo Cánovas1
  • Simon M. Laws4,5
  • Tenielle Porter4,5
  • Michael Weiner6
  • Colin L. Masters7
  • Hamid R. Sohrabi8,9
  • Jurgen Fripp3
  • Paul Maruff10
3 more authors
  • Victor L. Villemagne11
  • Christopher C. Rowe12,13
  • for the Alzheimer's Disease Neuroimaging Initiativethe Australian Imaging BiomarkersLifestyle flagship study of ageing
13 affiliations
  1. 1The Australian e‐Health Research Centre CSIRO Melbourne Victoria Australia
  2. 2School of Computing Technologies RMIT University Melbourne Victoria Australia
  3. 3The Australian e‐Health Research Centre CSIRO Brisbane Queensland Australia
  4. 4Centre for Precision Health Edith Cowan University Joondalup Western Australia Australia
  5. 5Collaborative Genomics and Translation Group School of Medical and Health Sciences Edith Cowan University Joondalup Western Australia Australia
  6. 6Center for Imaging of Neurodegenerative Diseases University of California‐San Francisco San Francisco California USA
  7. 7Alzheimer's Research Australia University of Western Australia Nedlands Western Australia Australia
  8. 8Centre for Healthy Ageing Health Futures Institute Murdoch University Murdoch Western Australia Australia
  9. 9School of Psychology Murdoch University Murdoch Western Australia Australia
  10. 10Cogstate Ltd Melbourne Victoria Australia
  11. 11Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA
  12. 12Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia
  13. 13Department of Molecular Imaging & Therapy Austin Health Heidelberg Victoria Australia
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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.

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Cite

BibTeXRIS
BibTeX
@article{shishegar2026optimized,
  title = {{Optimized amyloid‐β PET centiloid and cognitive cutoffs predict progression from mild cognitive impairment to Alzheimer's dementia}},
  author = {Rosita Shishegar and Vincent Doré and Pierrick Bourgeat and James D. Doecke and Rodrigo Cánovas and Simon M. Laws and Tenielle Porter and Michael Weiner and Colin L. Masters and Hamid R. Sohrabi and Jurgen Fripp and Paul Maruff and Victor L. Villemagne and Christopher C. Rowe and for the Alzheimer's Disease Neuroimaging Initiativethe Australian Imaging BiomarkersLifestyle flagship study of ageing},
  journal = {Alzheimer's \& Dementia},
  year = {2026},
  month = nov,
  doi = {10.1002/alz.71892},
  url = {https://doi.org/10.1002/alz.71892},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Optimized amyloid‐β PET centiloid and cognitive cutoffs predict progression from mild cognitive impairment to Alzheimer's dementia
AU  - Rosita Shishegar
AU  - Vincent Doré
AU  - Pierrick Bourgeat
AU  - James D. Doecke
AU  - Rodrigo Cánovas
AU  - Simon M. Laws
AU  - Tenielle Porter
AU  - Michael Weiner
AU  - Colin L. Masters
AU  - Hamid R. Sohrabi
AU  - Jurgen Fripp
AU  - Paul Maruff
AU  - Victor L. Villemagne
AU  - Christopher C. Rowe
AU  - for the Alzheimer's Disease Neuroimaging Initiativethe Australian Imaging BiomarkersLifestyle flagship study of ageing
PY  - 2026
DA  - 2026/11/05
JO  - Alzheimer's & Dementia
DO  - 10.1002/alz.71892
UR  - https://doi.org/10.1002/alz.71892
AB  - 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.
SN  - 1552-5260
SN  - 1552-5279
ER  -