ApoE ε4 status in pre‐dementia risk states, mild behavioural impairment and subjective cognitive decline, and the risk of incident cognitive decline
Bibliographic record
Abstract
Abstract Background Dementia has an increasing global burden with over 40 million affected individuals. With sub‐optimal advances in drug development, there is an increasing shift to determine risk of dementia in the non‐demented population. Assessment of neuropsychiatric symptoms (NPS) may offer an opportunity to capture the at‐risk group earlier. Mild Behavioural Impairment (MBI) is a validated neurobehavioural syndrome, characterized by the emergence of sustained NPS in older adults as an at‐risk state for dementia. Cognitively, subjective cognitive decline (SCD) is a dementia at‐risk group in which cognitive symptoms are reported in the absence of objective findings. The apolipoprotein epsilon 4 (ApoE ε4) gene is a well‐known risk marker for dementia. We aim to determine the frequency of ApoE homozygosity in SCD, stratified by MBI status cross‐sectionally, and calculate the hazard of incident cognitive decline in this group longitudinally. Method Data from 5005 participants in the National Alzheimer’s Coordinating Center (NACC) were used to capture older adults who were cognitively normal, but had subjective cognitive complaints (SCD). We determined MBI status (+/‐) using a previously published transformation algorithm of NPI‐Q scores. We tabulated ApoE genotype in both groups. We compared proportion of ApoE homozygousity (APOE ε4+/+)in the MBI+ versus the MBI‐ group. Additionally, a Cox proportional hazards regression will be done to capture hazard of incident mild cognitive impairment in MBI+ versus MBI‐. Result A two‐sample test of proportions of MBI+/‐ status stratified by ApoE ε4+/+resulted in significant differences between groups with homozygosity more frequent in MBI+ versus MBI‐ (p<0.001). We will also present the results of the Cox proportional hazards regression analysis. Conclusion In older adults with subjective cognitive decline, ApoE ε4 allele homozygosity was more frequently seen in the MBI+ group. These findings provide additional evidence for the utility in determining MBI status in SCD.
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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 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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) | 0.002 | 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".