P3‐100: APOE‐ε.4 status modulates the impact of cerebral white matter disease on cognition in Alzheimer's disease
Bibliographic record
Abstract
The APOE-ε4 allele has been established as a risk factor for AD, but research into its association with cerebral ischemia has been inconsistent. We determined to investigate white matter disease as a surrogate marker for cerebral ischemia and its relationship with APOE-ε4 status and cognitive performance. We identified AD patients participating in research studies at the National Neuroscience Institute, Singapore having undergone APOE testing, MRI brain and cognitive battery consisting of the Mini-Mental State Exam (MMSE), Montreal Cognitive Assessment (MOCA), Frontal Assessment Battery (FAB) and Alzheimer's Disease Assessment Scale (ADAS-11). White matter hyperintensities (WMH) were quantified using the modified Fazekas scale (0-12) on T2-weighted MR sequence and medial temporal atrophy (MTA) was graded using the Scheltens scale (0-4) on coronal SPGR sequences. MRI rating was performed blinded to clinical and cognitive status. We performed analysis of variance to evaluate the relationship between WMH and cognitive scores, and Spearman's rank correlation analysis to determine the relationship between APOE-ε4 status, degree of MTA, WMH load and cognitive scores. 54 patients fulfilled the required criteria. 17 had no WMH, 18 had mild WMH and 19 had moderate-high WMH. Patients with increasing WMH performed poorer on the MMSE, MOCA, FAB and ADAS-11. There was a significant correlation between poorer performance on colour-trail testing (P=0.021), digit cancellation (P=0.036) and category fluency (P=0.043) with higher WMH load. Geriatric Depression Scale scores were also associated with higher WMH (P=0.042). 18 patients tested positive for APOE-ε4. APOE-ε4 status did not significantly influence the correlation between MTA and cognitive scores, but influenced the correlation between WMH and cognition. Correlation between poorer MOCA (r=−0.34; P=0.05) and FAB (r=−0.31; P=0.08) scores with greater WMH load was approaching statistical significance in the APOE-ε4 negative group while the corresponding correlation was weaker in the APOE-ε4 positive group. WMH adversely influences cognitive function in AD. APOE-ε4 status modulates this association with APOE-ε4 negative patients demonstrating a strong correlation between WMH load and cognition while APOE-ε4 positive patients having a weaker correlation. This information would be useful in designing AD clinical trials as the modulatory effect of APOE-ε4 would need to be considered.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.003 | 0.001 |
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".