Lower Estimated Glomerular Filtration Rate Is Associated with Cognitive Decline and Longitudinal Structural Brain Changes over Six Years
Bibliographic record
Abstract
Background: Chronic kidney disease (CKD) is characterized by albuminuria and/or reduced estimated glomerular filtration rate (eGFR). CKD is linked to cognitive deficits and structural alterations, such as brain atrophy. The mechanisms connecting decreased kidney function, cognitive impairment, and brain function are not yet fully understood. Here, we examined the correlation between eGFR, cognition, and longitudinal brain structure. Methods: We analyzed a population-based sample of 15,897 participants (53.9 ± 7.5 years old, 49% women) from the CARTaGene cohort in Quebec, Canada. We conducted multivariate linear regressions to explore the relationship between baseline eGFR and cognitive performance. Vertex-based cortical surface analysis was done on the T1-weighted brain MRI scans acquired in 1367 participants six years after baseline to examine whether cortical thickness associated with baseline eGFR adjusting for age, sex, body mass index, vascular risk factors, and white matter lesion volume. Gene set enrichment analysis was done to identify the genetic features of regions where eGFR associated with thickness. Results: Cognitive performance declined with decreasing eGFR after adjusting for age, sex, income, education, smoking, alcohol intake, vascular risk factors, body mass index, and psychoactive medication use (P<0.001). Lower eGFR associated with cortical thinning in frontal and posterior regions and with increases in the temporal and cingulate areas (Figure 1). Brain regions exhibiting lower eGFR-associated thinning were enriched for mitochondrial gene expression, whereas regions with increased thickness were enriched for genes involved in protein-containing complex remodeling, with apolipoprotein E and angiotensinogen being key elements. Conclusions: Baseline eGFR is associated with cognition and longitudinal brain structural changes in regions with specific gene expression characteristics. Funding: Government Support - Non-U.S.Brain maps showing the regions where lower eGFR was significantly associated with cortical thinning.
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".