SP628THE APOE4 VARIANT IS ASSOCIATED TO EXECUTIVE FUNCTIONS IMPAIRMENT IN PATIENTS ON CHRONIC DIALYSIS
Bibliographic record
Abstract
INTRODUCTION AND AIMS: The prevalence of cognitive impairment (CI) in patients with chronic kidney disease is much higher than in general population and is between 30-80% in patients receiving dialysis.Among dialysis patients, CI is associated with lower compliance, lower quality of life, with consequent increased risk of morbidity, hospitalization and mortality. The pathophysiological mechanisms causing CI in dialysis are multifactorial, but still not clearly understood. Potential causes include: vascular co-morbidities and factors associated with uremia and dialysis such as oxidative stress, exchange of fluids, lowering of cerebral blood flow, etc. Apolipoprotein E (apoE) is the most abundant apolipoprotein. It has six genotypes (ε2/ε2, ε2/ε3, ε3/ε3, ε/ε4, ε3/ε4, ε4/ε4) originating from 3 different alleles (ε2, ε3, ε4). The ApoE4 isoform promotes the accumulation of amyloid-β (Aβ), slows the elimination of lipoproteins, with a consequent increase in plasma cholesterol levels. Accumulation and aggregation of Aβ in the brain is an initiating step in the pathogenesis of Alzheimer's disease (AD). The ε4 allele of apoE gene is the strongest genetic risk factor for late-onset AD. To date, no evidence of the possible role of ApoE in CI in dialysis is known. The aim of our study was, therefore, to evaluate the association between the CI and the isoforms of the ApoE gene in a cohort of dialysis patients. METHODS: The CI was evaluated on a cohort of patients in dialysis treatment without established neurological disease. For the determination of global CI was used the Montreal Cognitive Assessment (MoCA), a test designed as a rapid screening instrument for mild cognitive dysfunction. The CI was defined as a score at MoCA≤24. The Trail Making Test (TMT A-B) was used for the evaluation of executive functions (FE) and mental flexibility. In this test, the number of seconds used to complete the task is measured. Lower scores indicate better cognitive function. Polymorphisms of the ApoE gene were analyzed after genomic DNA extraction through: Polymerase Chain Reaction (PCR), Enzymatic Digestion and Polyacrylamide gel electrophoresis. RESULTS: Were enrolled 41 patients (29/12 M / F), aged 59.8 ± 12.3 (28 HD, 13 PD). 82.9% of patients showed CI at the MoCA, while 30% showed a FE deficiency at TMT. 19.5% of patients showed the ApoE4 variant. No significant difference at MoCA test was found between ApoE4 variant vs. E2/E3 carriers. The results at the TMT showed that 62.5% of patients with ApoE4 had impairment of FE compared to 18.2% of those carrying ApoE2-3 allele (p = 0.03). The patients with FE deficiency showed significantly lower levels of Albuminemia (p = 0.02) and higher levels of PCR (p = 0.04). CONCLUSIONS: In conclusion, our results suggest that ApoE gene is not associated with global CI in dialysis, but only with FE deficiencies. Since FE impairment is typically found in dementia of vascular origin, our results suggest that the pathophysiological factors of CI in dialysis patients may be mainly atherosclerotic in nature.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.003 | 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".