P1‐008: Regional Gray Matter Volume and Default Mode Network Connectivity are Associated with Age Relative to Parental Symptom Onset in Sporadic Alzheimer’s Disease
Bibliographic record
Abstract
In autosomal-dominant familial Alzheimer’s disease, individual age of symptom onset correlates with parental onset age. Various AD biomarkers precede dementia onset and show increasing abnormality as mutation carriers approach their parent’s onset age. We investigated whether this same principle applies in individuals with a family history of sporadic AD. We explored the association between age relative to parental symptom onset (aPSO) and AD biomarkers in PREVENT-AD, a cohort of cognitively intact persons aged 60+ with a parental history of AD. In 219 individuals, we assessed structural magnetic resonance (MR) images for regional gray matter (GM) volume, as well as functional brain connectivity (resting state fMRI) within the default mode network (DMN). Structural volumes were preprocessed and analyzed with SPM12, using the DARTEL method to define a population-specific template. Voxel-based morphometry (VBM) analysis was performed assessing the relation of aPSO with GM volume, adjusting for age, gender, ApoE4 status and total intracranial volume. Functional connectivity data were preprocessed and analyzed using NIAK. The association between aPSO and functional connectivity was explored within DMN regions defined on an independent dataset, again controlling for age, gender, ApoE4 status, as well as motion. VBM analysis revealed a region in the medial prefrontal cortex (mPFC) that displayed reduced GM volume as individuals approached their parental age of onset (p < 0.05 FWE corrected). Relaxing the statistical threshold revealed an atrophy pattern that extended into the posterior cingulate, the left middle temporal lobe, and large portions of the mPFC, as well as in the thalamus (Figure 1). The affected regions overlapped substantially with the DMN (Figure 2). We next carried out functional connectivity analysis within DMN subregions. As individuals approached their parental age of onset, within-region connectivity decreased in the anterior DMN and the lateral DMN (FDR < 0.05), with a similar trend for the posterior DMN (FDR p< 0.1; Figure 3).
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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) | 0.000 | 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 | 0.000 |
| 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".