CSF biomarkers for Alzheimer Disease are associated with spatial cognition in cognitively normal older adults
Bibliographic record
Abstract
Abstract Background Spatial cognition has emerged as a promising cognitive fingerprint for the detection of Alzheimer’s disease (AD). Despite evidence that spatial cognition is highly sensitive to AD dementia and is apparent even in adults at‐genetic‐risk of AD, the association between spatial cognition and AD biomarkers in cognitively normal adults is unknown. Method This study leverages data from the European Prevention of Alzheimer’s Dementia Consortium, a multinational observational study of clinically normal adults initiated in 2016 that includes two digital spatial paradigms: The Supermarket Task (SMT)and the Four Mountains Task (4MT;Fig1). Using a mixed model approach with random intercepts, we investigated cross‐sectional associations between cerebrospinal fluid (CSF) β‐amyloid1‐42 (Aβ1‐42) and phosphorylated tau (p‐tau181) with task performance (N = 1672; mean age = 68.08[SD = 6.96]). Result Five hundred and forty‐nine (32.8%) participants had abnormal levels of CSF Aβ1‐42 and p‐tau181. Across the whole sample, higher p‐tau181 concentrations were associated with greater spatial disorientation from the starting location on the SMT (r = ‐0.449, p = <0.001). There was a small association with CSF Aβ1‐42(r = 1.984, p = 0.003; Fig2A‐B). Higher levels of CSF p‐tau181 were associated with more 4MT feature memory errors (r = ‐0.570, p<0.001). There was also a main effect of Aβ1‐42 on 4MT performance (r = 0.301, p = <0.001; Fig2C‐D). Entorhinal cortex and hippocampal volumes both predicted better performance on both tasks (r’s = 0.37‐0.57; Fig3). Post hoc analyses revealed a significant interaction between sex and hippocampal volume, indicating that the association between hippocampal volume and recall of environmental features was stronger in males than females. Finally, volume of the entorhinal cortex, but not the hippocampus, mediated the relationship between p‐tau181 and performance on both spatial tasks (Fig4). Conclusion Our results suggest that spatial tasks are sensitive to CSF p‐tau181 and to a lesser extent Aβ1‐42 in preclinical AD. Given the well‐validated digital platform that these tasks are founded on, these tools provide access to racially and ethnically diverse individuals for preclinical AD trial registries via unsupervised assessment.
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 | 0.004 |
| 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 | 0.000 |
| 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".