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Biomarker affliction classes contribute additively to observed dementia severity and prospective conversion risk
Donald R Royall1,2, Raymond F Palmer3,
1Department of Psychiatry, the University of Texas Health Science Center, San Antonio, TX, USA.
Journal of Alzheimer'S Disease : JAD
|June 24, 2026
Summary
The number of dementia biomarkers, not just Alzheimer's disease (AD)-specific ones like amyloid-beta (Aβ), significantly impacts dementia severity and conversion risk. Adipokine biomarkers showed a stronger effect than Aβ.
Area of Science:
- Neurology
- Biomarker Research
- Dementia Studies
Background:
- Dementia is influenced by multiple independent biomarkers, including but not limited to Alzheimer's disease (AD)-specific markers.
- Understanding the combined impact of various biomarkers is crucial for assessing dementia progression.
Purpose of the Study:
- To evaluate how multiple biomarker afflictions affect dementia severity.
- To determine the relationship between biomarker load and clinical outcomes like the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and time to dementia conversion.
Main Methods:
- Utilized data from 988 amyloid PET-positive subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
- Categorized subjects based on resilience or affliction by central nervous system amyloid-beta (Aβ), plasma adipokines, and/or neurodegeneration.
- Assessed impact on CDR-SB scores and time to dementia conversion.
Main Results:
- Dementia severity (CDR-SB) increased with the number of afflicting biomarkers, regardless of dementia status.
- Plasma adipokines showed the strongest association with severity (r=0.33), while Aβ had the weakest (r=0.18).
- The number of afflicting biomarkers independently predicted conversion risk over 48 months and explained 25.2% of CDR variance.
Conclusions:
- Dementia severity in amyloid PET-positive individuals is determined by combinations of biomarkers, not solely by Aβ.
- Plasma adipokines and neurodegeneration play significant roles, independent of or in conjunction with Aβ.
- Findings suggest a need to reconsider the A/T/N diagnostic framework to include a broader range of biomarkers.
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