Abstract P337: Clonal Hematopoiesis of Indeterminate Potential and Cognitive Decline in Chronic Kidney Disease Patients
Bibliographic record
Abstract
Introduction: Patients with chronic kidney disease (CKD) are at substantially increased risk of dementia. Clonal hematopoiesis of indeterminate potential (CHIP), caused by clonal expansion of blood cells with somatic mutations in certain driver genes, is an established risk factor for cardiovascular diseases, including cerebral vascular disease. In contrast, CHIP was recently shown to be associated with a decreased risk of Alzheimer’s disease. Given emerging evidence of a key role of vascular compared to neurodegenerative mechanisms in CKD-related dementia, the relation of CHIP with cognitive decline in CKD patients needs clarity. We investigated the prospective associations of CHIP with cognitive impairment in a cohort of patients with CKD. Methods: Our study included 1989 participants aged 65 years or older from the Chronic Renal Insufficiency Cohort. Participants underwent high-depth targeted gene sequencing to ascertain CHIP status. Cognitive function was assessed by four cognitive tests (see Table ). For each test, incident cognitive impairment was defined as a test score one standard deviation worse than the baseline group mean. Sequential Cox proportional hazards models tested associations between CHIP and cognitive impairment after adjusting for demographics (model 1), clinical measures (model 2), and APOE genotype in a subset with available data (model 3). Results: CHIP carriers were significantly less likely to experience impairment in attention (Trails A) and executive function (Trails B) in our fully adjusted models ( Table ). There were no significant associations between CHIP and impairment in global cognition (3MS) or verbal memory (Buschke). There were no differences in the associations of CHIP with cognitive impairment across sex or race groups (data not shown). Conclusions: In patients with CKD, we observed markedly reduced risks of impairment in cognitive domains of attention and executive function. Further studies are needed to confirm our findings and evaluate mechanisms of these relations.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".