Abstract
Cognitive impairment is prevalent in patients with chronic kidney disease (CKD), but its underlying mechanisms are obscure. Here, we test the hypothesis that exaggerated orthostatic blood pressure reduction mediates the effects of renal failure on global cognition and memory. A total of 160 study subjects were recruited, including 80 dialysis patients and 80 controls. Global cognition was evaluated using the Montreal Cognitive Assessment (MoCA), and episodic memory was evaluated using the auditory verbal learning test (AVLT). Autonomic function was evaluated via the low-frequency to high-frequency ratio (LF/HF) through heart rate variability analysis. Compared with the controls, the dialysis patients had significantly lower MoCA and AVLT scores (including learning memory, short recall memory, and delayed recall memory) (all p < 0.001). They also showed exaggerated orthostatic systolic blood pressure reductions (all p ≤ 0.001). The maximum orthostatic systolic blood pressure reduction was independently and negatively associated with short (β = -0.05, p = 0.029) and delayed (β = -0.05, p = 0.035) recall memory in dialysis patients but not in controls. Mediation analysis demonstrated that maximum orthostatic systolic blood pressure reduction mediates 13.8% of the effect of end-stage renal disease (ESRD) on short recall memory (p = 0.04). After adjustment for LF/HF, the negative association between maximum orthostatic blood pressure reduction and short recall score remained significant (p = 0.049), while the association between maximum orthostatic blood pressure reduction and delayed recall score became nonsignificant, with a marginal p value of 0.062. Our study reveals that exaggerated orthostatic blood pressure reduction is a possible explanation for ESRD-associated memory deficits.
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