SP628THE APOE4 VARIANT IS ASSOCIATED TO EXECUTIVE FUNCTIONS IMPAIRMENT IN PATIENTS ON CHRONIC DIALYSIS

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 (e2/e2, e2/e3, e3/e3, e/e4, e3/ e4, e4/e4) originating from 3 different alleles (e2, e3, e4). The ApoE4 isoformpromotes the accumulation of amyloid-b (Ab), slows the elimination of lipoproteins, with a consequent increase in plasma cholesterol levels. Accumulation and aggregation of Ab in the brain is an initiating step in the pathogenesis of Alzheimer's disease (AD). The e4 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 (29/12M/ 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.