Genetic risk for Alzheimer disease, cognition and Mild Behavioral Impairment in healthy older adults
Bibliographic record
Abstract
BACKGROUND: Mild Behavioral Impairment (MBI) is a neuropsychiatric syndrome describing later-life emergent apathy, mood/anxiety symptoms, impulse dyscontrol, social inappropriateness and psychosis that are not attributable to psychiatric diagnoses. MBI is an at-risk state for incident cognitive decline and dementia, and is associated with dementia biomarkers including amyloid beta; and neurofilament light. Thus, MBI may be an early clinical marker of neurodegenerative disease. In this study, we hypothesized that stratification by MBI in a cognitively normal sample would moderate the signal between Alzheimer disease (AD) genetic risk and cognition. METHODS: Genetic, cognitive and MBI data was available for 3,126 PROTECT study participants over 50 without dementia. A general cognitive composite score was constructed based on scores on paired associates learning, digit span, self-ordered search and verbal reasoning. MBI was assessed using the MBI Checklist. Polygenic scores for AD were split by tertile (representing low, medium and high risk) and the sample was stratified by MBI into those with no symptoms and those with any symptoms. RESULTS: AD genetic risk was associated with poorer cognition in the MBI strata only (MBI: F(2,1746)=4.95, p=0.007; no MBI: F(2,1366)=0.72, p=0.49). The mean difference between low and high genetic risk groups was significant (p=0.005) and the standardised effect size in the MBI sample was higher than in the whole sample. CONCLUSIONS: These findings justify MBI screening to enrich samples with at-risk individuals, and underscore the importance of late-life neuropsychiatric symptoms in cognitive ageing.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".