Lydia Trudel, Joseph Therriault, Arthur C. Macedo, Stijn Servaes, Seyyed Ali Hosseini, Gleb Bezgin, Nesrine Rahmouni, Tevy Chan, Jaime Fernandez-Arias, Étienne Aumont, Yi-Ting Wang, Yansheng Zheng, Brandon Hall, Robert Hopewell, Chris Hung-Hsin Hsiao, Arthur W. Toga, Meredith N. Braskie, Karin L. Meeker, Jean-Paul Soucy, Serge Gauthier, Paolo Vitali, Sid E. O'Bryant, Tharick A. Pascoal, Pedro Rosa-Neto
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Amyloid-positive participants were staged according to the Alzheimer's Association biological staging framework (A+T<sub>2</sub>-/A+T<sub>2MTL</sub>+/A+T<sub>2MOD</sub>+/A+T<sub>2HIGH</sub>+).</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Cognitively unimpaired (CU) individuals in the A+T<sub>2MTL</sub>+, A+T<sub>2MOD</sub>+, and A+T<sub>2HIGH</sub>+ biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to non-AD CU individuals. In individuals with MCI, advanced tau stage was associated with an 83% likelihood of developing dementia over 4 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression compared to amyloid-PET (positron emission tomography) status, tau-PET status, and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than non-AD controls, with the A+T<sub>2HIGH</sub>+ stage showing the steepest rate of decline (<i>p</i> < 0.001).</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Our results highlight the prognostic value of biological AD staging.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Cognitively unimpaired (CU) individuals in all tau-PET (positron emission tomography)–positive biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to individuals without AD.</li>\n \n <li>In individuals with mild cognitive impairment (MCI), only the A+T<sub>2HIGH</sub>+ stage reached a point where 50% of individuals had progressed to all-cause dementia, after 2.36 years.</li>\n \n <li>Biological AD staging demonstrated superior accuracy in predicting clinical progression to dementia compared to other PET biomarkers and demographic information.</li>\n \n <li>All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than individuals without AD, with the A+T<sub>2HIGH</sub>+ stage showing the steepest rate of decline.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70624","citationCount":"0","resultStr":"{\"title\":\"Rates of clinical progression according to biological Alzheimer's disease stages\",\"authors\":\"Lydia Trudel, Joseph Therriault, Arthur C. 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Rates of clinical progression according to biological Alzheimer's disease stages
INTRODUCTION
Predicting the rate of cognitive decline and the likelihood of progression to dementia remains a critical unmet need in clinical settings.
METHODS
We assessed progression to mild cognitive impairment (MCI) and all-cause dementia in 492 individuals from the TRIAD, ADNI, and HABS-HD cohorts followed for an average of 2.49 years. Amyloid-positive participants were staged according to the Alzheimer's Association biological staging framework (A+T2-/A+T2MTL+/A+T2MOD+/A+T2HIGH+).
RESULTS
Cognitively unimpaired (CU) individuals in the A+T2MTL+, A+T2MOD+, and A+T2HIGH+ biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to non-AD CU individuals. In individuals with MCI, advanced tau stage was associated with an 83% likelihood of developing dementia over 4 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression compared to amyloid-PET (positron emission tomography) status, tau-PET status, and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than non-AD controls, with the A+T2HIGH+ stage showing the steepest rate of decline (p < 0.001).
DISCUSSION
Our results highlight the prognostic value of biological AD staging.
Highlights
Cognitively unimpaired (CU) individuals in all tau-PET (positron emission tomography)–positive biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to individuals without AD.
In individuals with mild cognitive impairment (MCI), only the A+T2HIGH+ stage reached a point where 50% of individuals had progressed to all-cause dementia, after 2.36 years.
Biological AD staging demonstrated superior accuracy in predicting clinical progression to dementia compared to other PET biomarkers and demographic information.
All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than individuals without AD, with the A+T2HIGH+ stage showing the steepest rate of decline.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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