Title : Chronic Kidney Disease and Associated Cardiovascular Dysfunction exacerbate the Progression of Cognitive Impairment
Abstract:
Introduction: In end-stage chronic kidney disease (CKD) (stages 4-5) the prevalence of cognitive impairment (CI) has been estimated at 30-60%, twice the values observed in age- and sex-matched controls. Cardiovascular diseases (CVD) including hypertension and increased central arterial stiffness (CAS) accompany CKD development across all stages of this disease. CAS drives pulse pressure (PP) and pulsatile component index (PCI) increases and cerebral microvascular damage resulting in a reduction of blood supply to the brain hereby contributing to CI. Elevated PP and PCI are associated with higher mortality in CVD and CKD independently of BP. The aim of the study was to determine whether CKD potentiates CI development due to CAS and the resultant increase in the PCI, a major contributor to brain and renal microvasculature damage.
Methods: All research was performed in accordance with the guidelines and regulations set forth by the Declaration of Helsinki regarding the use and enrollment of human subjects in research. A total of 40 CKD patients (age 45-50 years and older, CKD stage 4, GFR 15-29, and Creatinine > 1mg/dL) and 30 age and sex- matched healthy control patients were enrolled with exclusion criteria (history of HIV, hepatitis, malignancies, admission and/or surgery for trauma, head injury and pregnancy at time of enrollment). Blood pressure (systolic and diastolic blood pressure (SBP, DBP) was measured, clinical blood work, echocardiography (ECHO) and mini-mental state examination (MMSE) was performed as well as levels of amyloid beta-40 (Aβ-40) measured. PCI was calculated as difference between peak systolic and end diastolic flow velocity, divided by the flow velocity. The data were analyzed by unpaired two-tailed t-test, Pearson correlation with P values adjusted for false discovery rate, and are presented as mean ± SEM.
Results: CKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume (estimated by ECHO), lower LV ejection fraction, higher plasma NT-proBNP and AST (CVD markers), glucose, triglycerides, plasma Aβ-40 (Alzheimer’s disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (p<0.05). Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of blood pressure, and negatively correlated with plasma ASP, a marker of CVD.
Conclusion: Higher PP, PCI, plasma Aβ-40 and lower score in MMSE in CKD patients supports our hypothesis that cardiovascular remodeling in CKD patients contributes to the development and progression of CI.
What will audience learn from your presentation?
- The present study demonstrates that CKD potentiates cognitive impairment due to central arterial stiffening and the resultant increase in the pulse pressure, a major contributor to brain and renal microvasculature damage.
- The present study demonstrates that targeting the pro-fibrotic markers and fibrosis processes within the arterial wall and renal tissue will ameliorate cognitive impairment in CKD
- The present study offers crucial evidence and a cost effective, non-invasive predictive modality demonstrating the efficacy of the proposed panel of biomarkers.
