Apathy and <i>APOE</i> in mild behavioral impairment, and risk for incident dementia
Bibliographic record
Abstract
Abstract Introduction Mild behavioral impairment (MBI) is a high‐risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) in dementia but can also develop in persons with normal cognition (NC) or mild cognitive impairment (MCI). The later‐life emergence and persistence of apathy as part of the MBI syndrome may be a driving factor for dementia risk. Therefore, we investigated MBI‐apathy–associated progression to dementia, and effect modification by sex, race, cognitive diagnosis, and apolipoprotein E ( APOE ) genotype. Methods Dementia‐free National Alzheimer's Coordinating Center participants were stratified by persistent apathy status, based on Neuropsychiatric Inventory (NPI)–Questionnaire scores at two consecutive visits. Hazard ratios (HRs) for incident dementia for MBI‐apathy and NPI‐apathy relative to no NPS, and MBI‐apathy relative to no apathy, were determined using Cox proportional hazards regressions, adjusted for baseline age, sex, years of education, race, cognitive diagnosis, and APOE genotype. Interactions with relevant model covariates were explored. Results Of the 3932 participants (3247 with NC), 354 had MBI‐apathy. Of all analytic groups, MBI‐apathy had the greatest dementia incidence (HR = 2.69, 95% confidence interval [CI]: 2.15–3.36, P < 0.001). Interaction effects were observed between cognitive diagnosis and APOE genotype with the NPS group. The contribution of apathy to dementia risk was greater in NC (HR = 5.91, 95% CI: 3.91–8.93) than in MCI (HR = 2.16, 95% CI: 1.69–2.77, interaction P < 0.001) and in all APOE genotypes, was greatest in APOE ɛ3 (HR = 4.25, 95% CI: 3.1–5.82, interaction P < 0.001). Discussion Individuals with MBI‐apathy have a markedly elevated risk for future dementia, especially when symptoms emerge in those with NC. Both cognitive status and APOE genotype are important moderators in the relationship between MBI‐apathy and incident dementia. MBI‐apathy may represent a group in whom apathy is a preclinical or prodromal manifestation of dementia and identify a precision medicine target for preventative interventions.
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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 | 0.003 |
| 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 | 0.001 | 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".