MBI‐apathy, ApoEɛ2, and risk for Alzheimer disease dementia
Bibliographic record
Abstract
Abstract Background Apathy, characterized by decreased interest, initiative, and emotional reactivity, is amongst the most common neuropsychiatric symptoms in dementia. However, apathy can emerge before dementia and constitutes a domain of mild behavioral impairment (MBI), an at‐risk state for incident cognitive decline and dementia. MBI‐apathy is the de novo emergence of persistent apathy in dementia‐free older adults and may be a driving factor in dementia risk conferred by MBI. Apolipoprotein E (ApoE) is a risk marker for Alzheimer disease (AD) dementia. Compared to ApoEɛ3 homozygotes, ApoEɛ2 carriers are 40% less likely to develop AD while ApoEɛ4 carriers are 3.2‐14.9 times more likely. We investigated the association between MBI‐apathy, ApoE, and incident dementia. We hypothesized that ɛ2 would have protective effects for MBI‐apathy associated risk, compared to ɛ3 and ɛ4. Method Dementia‐free participants in the National Alzheimer’s Coordinating Centre were stratified as MBI‐apathy and no‐NPS until dementia diagnosis, based on Neuropsychiatric Inventory Questionnaire scores at 2 consecutive visits. ApoE genotypes were categorized by ɛ2 (ɛ2/ɛ2, ɛ2/ɛ3), ɛ3 (ɛ3/ɛ3), and ɛ4 (ɛ4/ɛ3, ɛ4/ɛ4) alleles. Group characteristics were contrasted to determine covariate inclusion in regression modelling. Cox regressions assessed risk of incident dementia and included an interaction term for MBI‐apathy and ApoE allele. Results Of the 3,644 participants (3,022 Normal‐Cognition); 314 had MBI‐apathy (Table 1). Significant main effects were found for MBI‐apathy and incident dementia (HR:2.51, 95% CI:1.99‐3.17, p<0.001) as well as interaction effects with ApoE. In MBI‐apathy (ɛ3 as reference), the ɛ2 group had a 60% lower dementia risk (adjusted HR:0.40, 95% CI:0.19‐0.85) while ɛ4 had a 16% higher risk (adjusted HR:1.16, 95% CI:0.80‐1.69) (Figure 1). Of the 125 participants with apathy who progressed to dementia, 80.8% had AD. In the no‐NPS group (ɛ3 as reference), ɛ2 individuals had a 17% lower dementia risk (adjusted HR:0.83, 95% CI:0.52‐1.33) while ɛ4 individuals had a 177% higher risk (adjusted HR:2.77, 95% CI:2.13‐3.59) (Figure 2). Conclusion To our knowledge, this is the first study examining the relationship between MBI‐apathy and ApoE status in determining dementia risk. Results suggest that ApoE modifies the association between MBI‐apathy and incident dementia with the ɛ2 allele acting as a protective factor.
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 | 0.003 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".