Putative Neurostructural Phenotypes of Genetic Risk for Alzheimer's Disease in Youth with Bipolar Disorder
Bibliographic record
Abstract
BACKGROUND: Bipolar disorder (BD) is linked to an increased risk of Alzheimer's disease (AD). It is well established that the AD process long precedes onset of clinical symptoms, highlighting the importance of understanding the early genesis of AD. Evaluating genetic risk for AD in relation to brain structure in youth may provide insights regarding regional neurostructural susceptibility to AD. The anterior cingulate cortex has been implicated in both BD and in relation to polygenic risk scores (PRS) for AD in healthy children. METHODS: This study investigated AD-PRS derived from adult studies, both as main effect and interaction with diagnosis, on brain structure using T1-weighted magnetic resonance imaging data. Participants included 112 youth aged 13-20 years (n = 67 BD; n = 45 healthy controls [HC]). AD-PRS were calculated using PRS-CS-auto. General linear models assessed the association between AD-PRS and regional brain structure, controlling for age, sex, intracranial volume, and the first two genetic principal components. Vertex-wise analyses and an anterior cingulate cortex region of interest analyses were conducted, as well as sex-stratified analyses. RESULTS: In the whole sample, higher AD-PRS was associated with lower superior temporal gyrus volume (p = 0.03). In interaction analyses, higher AD-PRS was associated with lower regional structure to a greater extent in the BD vs. HC group, including: superior temporal gyrus (p = 0.008) and precuneus (p = 0.01) volume, and rostral middle frontal (L: p <0.001; R: p = 0.03), caudal middle frontal (p = 0.001), superior frontal (p = 0.005), precentral (p = 0.049) gyri, and superior parietal lobule (p = 0.04) thickness. In sex-stratified analyses, higher AD-PRS was associated with lower superior parietal lobule surface area (p = 0.03) and volume (p <0.001) in females. In males, higher AD-PRS was associated with higher cortical thickness and volume in the supramarginal and rostral middle frontal gyri, respectively (p <0.001; p = 0.004). Region of interest analyses were not significant. CONCLUSION: Higher AD-PRS is associated with smaller brain structure metrics in youth with BD compared to HC. Findings also highlight potential sex differences. Future longitudinal studies should be conducted to investigate dynamic changes in the association between AD-PRS and brain structure across development.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".