Association of Alzheimer's genetic loci with mild behavioral impairment
Bibliographic record
Abstract
Mild behavioral impairment (MBI) describes the emergence of later-life neuropsychiatric symptoms (NPS) as an at-risk state for incident cognitive decline and dementia, and for some as a potential manifestation of prodromal dementia. How NPS mechanistically link to the development of mild cognitive impairment and Alzheimer's disease (AD) is not fully understood, with potential mechanisms including shared risk factors related to both NPS and cognitive impairment, or AD pathology promoting NPS. This is the first exploratory study to examine whether AD genetic loci as a genetic risk score (GRS), or individually, are a shared risk factor with MBI. Participants were 1,226 older adults (aged 72-79; 738 males; 763 normal cognition) from the Personality and Total Health Through Life project. MBI was approximated in accordance with Criterion 1 of the ISTAART-AA diagnostic criteria using a transformation algorithm for the neuropsychiatric inventory. A GRS was constructed from 25 AD risk loci. Binomial logistic regression adjusting for age, gender, and education examined the association between GRS and MBI. A higher GRS and APOE*ε4 were associated with increased likelihood of affective dysregulation. Nominally significant associations were observed between MS4A4A-rs4938933*C and MS4A6A-rs610932*G with a reduced likelihood of affective dysregulation; ZCWPW1-rs1476679*C with a reduced likelihood of social inappropriateness and abnormal perception/thought content; BIN1-rs744373*G and EPHA1-rs11767557*C with higher likelihood of abnormal perception/thought content; NME8-rs2718058*G with a reduced likelihood of decreased motivation. These preliminary findings suggest a common genetic etiology between MBI and traditionally recognized cognitive problems observed in AD and improve our understanding of the pathophysiological features underlying MBI.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".