The interplay between functional MRI measures of episodic memory and CSF measures of tau in healthy adults at risk of Alzheimer’s Disease
Bibliographic record
Abstract
Abstract Background Neural changes occur early in Alzheimer’s disease (AD). Longitudinal data on the relationship between AD pathology and brain activity, however, are sparse. Using an established cohort of cognitively unimpaired older adults (PREVENT‐AD) at risk of AD (due to familial incidence), we assessed the relationship between functional magnetic resonance imaging (fMRI) activity during episodic memory retrieval and cerebrospinal fluid (CSF) markers of tau and β‐amyloid. We aimed to test whether baseline fMRI signal predicts changes in CSF markers and vice versa. Method Three‐hundred and three participants (64.7±8.3yrs, 82 male) underwent task‐based fMRI of associative episodic memory retrieval at baseline, with longitudinal fMRI data for up to five timepoints with a 3, 12, 24, and 48‐month follow‐up. Region of Interest (ROI) analysis assessed retrieval activity (Fig.1A; t‐contrast differentiating hits for old stimuli from the correct rejection of new stimuli) in the bilateral precuneus and medial temporal lobe (MTL, Fig.1B‐1C). In a subset of participants (n = 117, 30 male), CSF was sampled to quantify t‐tau, p‐tau 181, and the ratio of β‐amyloid 1‐42 to p‐tau 181 (with another measurement 36‐months post‐baseline). Data were analyzed with random‐intercept linear mixed models, assessing changes in ROI activity and CSF markers over time. We tested whether baseline ROI activity predicted change in CSF markers and whether baseline CSF measures predicted change in ROI activity over time. Result Results indicate a significant decrease in precuneus activity over time, but not MTL, and an increase in t‐tau and p‐tau 181 (Fig.2A‐2D). No change was observed for β‐amyloid/p‐tau 181 ratio. We also observed a significant time by baseline MTL activity interaction on t‐tau (Fig.3) with higher baseline activity being associated with lower t‐tau in CSF over time. We observed no relationship between baseline CSF markers and functional activity. Conclusion While preliminary, these results suggest that baseline MTL retrieval activity may predict t‐tau (a marker of neurodegeneration) accumulation in the CSF of healthy adults at risk of AD. Further analyses of whole‐brain episodic memory responses, episodic memory task‐performance over time, and of positron emission tomography (PET) measures of regional tau and β‐amyloid, are critical to extend these findings further.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".