Plasma biomarkers associations with cognitive change in preclinical Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Blood biomarkers to detect Alzheimer’s disease pathology are needed as screening tools and to predict the onset of cognitive decline. Although there is increasing data on their potential usefulness across AD continuum, comprehensive comparisons of their ability to predict cognitive decline in cognitively unimpaired (CU) populations are still lacking. Method We studied 214 CU individuals from the ALFA+ cohort (Table 1), which had baseline measurements of plasma p‐tau181, p‐tau217, p‐tau231, t‐tau, GFAP, NfL and Ab42/40. All biomarkers were measured with Simoa, except for plasma p‐tau217 and t‐tau that were MSD‐based assay measures (Eli Lilly and Company ). Longitudinal measures of cognition (Preclinical Alzheimer Cognitive Composite [PACC]) at 3 years’ follow‐up were available. All participants remained CU at follow‐up. We tested the associations of baseline plasma biomarkers with PACC scores change (delta score computed as V2‐V1) using linear regression models adjusted by age, sex, education and time between neuropsychological visits. We further stratified by CSF Aβ‐status (Aβ+ if CSF Aβ42/40 <0.071) and interaction terms between each biomarker and Aβ‐status were evaluated. Finally, we studied the associations between baseline plasma biomarkers and cognitive change specifically in participants that displayed the steepest (<1SD) cognitive decline (“decliners”). Result In the whole sample, higher baseline plasma p‐tau181 (P=0.003) and t‐tau (P=0.007) were significantly associated with lower PACC scores at follow‐up. In CSF Aβ‐positive individuals, plasma p‐tau181, p‐tau231, t‐tau and NfL at baseline were significantly associated with cognitive decline while no significant associations were found in the Aβ‐negative group. The interaction with CSF Aβ status was significant only for plasma p‐tau231 (P=0.028) (Figure 1). In individuals that displayed a steeper decline (n = 33 [16% of the sample], Table 2), plasma p‐tau181, p‐tau217 and t‐tau were significantly associated with longitudinal change in PACC scores (Figure 2). Conclusion In preclinical AD, baseline plasma levels of p‐tau181, tau231, t‐tau and NfL are associated with cognitive decline at follow‐up. In the group of decliners, higher p‐tau181, p‐tau217 and t‐tau at baseline associate with cognitive change. These results have important implications for the consideration of plasma biomarkers for clinical trials targeting asymptomatic individuals or individuals with subtle cognitive decline.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".