Dementia associated with chronic kidney disease is accompanied by increase in plasma amyloid beta and cardiovascular dysfunction.

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In end-stage chronic kidney disease (CKD) the prevalence of cognitive impairment (CI) has been estimated at 30-60%. Cardiovascular diseases (CVD) including increased central arterial stiffness (CAS) accompany CKD development. 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. Measurements of systolic and diastolic blood pressure (SBP, DBP), echocardiography (ECHO), plasma amyloid beta-40 (Aβ-40), BUN, creatinine, aspartate aminotransferase (AST), brain natriuretic peptide (BNP), and mini-mental status examination (MMSE) were performed in 25 patients with stage IV CKD and in 22 age- and sex-matched healthy controls (Table 1). PCI was calculated as a function of SBP and DBP. 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. CKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume, lower LV ejection fraction, higher plasma BNP and AST (CVD markers), plasma Aβ-40 (Alzheimer's disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (Table 1). Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of BP, and negatively correlated with plasma ASP, a marker of CVD (Table 2). SBP and DBP did not correlate with cognitive parameters. Further investigation of the possible metabolic role of Aβ-40 in the development of CI in CKD patients, and whether plasma AST can be a marker of CI in CKD, will be assessed in the future studies. Higher PP, PCI and lower score in MMSE in CKD patients supports our hypothesis that cardiovascular remodeling in CKD is a key component of CI progression. Supported by the NIH Grant 1R15HL150721 (K.S.), and in part by NIH/NIA Intramural Research Program.