Research On The Characteristics And Mechanism Of Memory Impairment Related To End-stage Renal Disease

Part 1Memory deficit in patients on maintenance hemodialysis:Pattern and risk factorsBackground:Chronic kidney disease(CKD)has become one of the most important issue in global public health.The decline of renal function can lead to secondary injury of nearly all the other organs.Cognitive impairment,as a manifestation of central nervous injury,is prevalent in patients with CKD.Previous studies on CKD associated cognitive impairment have paid little attention to memory deficit,which can be detrimental to patients' quality of life as well as prognosis.The current study aims to explore the pattern of CKD associated memory deficit in patients with end-stage renal disease and its associated risk factors.Materials and Methods:Sixty patients on maintenance hemodialysis and 60 healthy controls(without CKD,cardiovascular diseases or neurologic diseases)were included.Patients and controls were frequency-matched by age,sex and education.The Montreal Cognitive Assessment(MoCA)was used to assess global cognition while the Auditory Verbal Learning Test(AVLT)was used for episodic memory evaluation.General clinical information,lab test results,blood pressure and pulse wave velocity were also recorded.Results:Compared with controls,patients had significantly lower scores of MoCA and AVLT(learning memory,short delayed recall,long delayed recall).The memory curve plot based on AVLT results demonstrate that patients had a similar memory curve from learning memory to short delayed memory,whereas their memory declined significantly from short delayed recall to long delayed recall while the controls'memory remained stable.Multiple stepwise regression analysis revealed that end-stage renal disease is associated with memory deficit independently.In the patients,education,sex,blood pressure,diabetes and previous cardiovascular diseases are independent predictors for memory scores.Conclusions:Our study reveals significant memory deficit with a special pattern(decline soon as time elapse)in patients on maintenance hemodialysis.We also confirmed that end-stage renal disease is associated with memory deficit independently and found that education,sex,blood pressure,diabetes and previous cardiovascular disease have independent effects on memory.Targeting these factors might be beneficial for memory in dialysis patients.Part ?Brain structure and function alterations in patients with end-stage renal disease:voxel-based morphometry and functional magnetic resonance imagingBackground:Patients with chronic kidney disease constitute a population at increased risk for cognitive impairment.The first part study of this thesis has shown that hemodialysis patients have significant impaired cognition and memory.However,the structural and functional basis of the brain for the cognitive impairment is still obscure.We aim to address this issue using voxel-based morphometry(VBM)and functional magnetic resonance imagingMaterials and Methods:The current study included 60 dialysis patients and 60 healthy controls.The two groups were frequency-matched by age,sex and education year.All participants were tested for global cognition and episodic memory.Brain structure and function were evaluated using magnetic resonance imaging with 3DT1 and BOLD(blood-oxygen-level dependent)sequences.VBM was used to calculate grey matter volume while ReHo(regional homogeneity)was calculated to assess brain activity.Results:VBM revealed that dialysis patients have significantly reduced grey matter volume in the following area:right cerebellum anterior lobe,bilateral cerebellum posterior lobe,right hippocampus,amygdala,parahippocampus gyrus,left medial frontal gyrus,left fusiform gyrus,bilateral caudate and subcallosal gyrus and left insula.fMRI showed that ReHo declined in dialysis in the left middle and inferior frontal gyrus,as well as in the right supra marginal gyrus.Correlation analysis demonstrated that the grey matter volume of the left insula correlated with global cognitive test score(r=0.35,p=0.007)and ReHo of left middle/inferior frontal gyrus correlated with learning memory test score(r=0.34,p=0.02).Conclusions:The current study demonstrates that dialysis patients are with diffuse cerebral atrophy,as well as reduced brain functional activity in certain areas.The structural and functional changes are associated with global cognitive and memory alteration.Our results could provide insight into brain pathological mechanisms for cognitive and memory impairment in dialysis patients.Part ?Orthostatic blood pressure change in patients with end-stage renal disease and its impact on memoryBackground:Cardiovascular diseases are prevalent in patients with chronic kidney disease(CKD).Due to accumulated risk factors,CKD patients are at increased risk of developing orthostatic hypotension.Previous studies indicated that orthostatic hypotension is associated with cognitive impairment in the general population.Our study in the first part has demonstrated that hemodialysis patients have significant and characteristic memory deficit.Here,we continue to explore the orthostatic blood pressure change in dialysis patients and its impact on memory ability.Materials and Methods:The current study included 60 patients on maintenance hemodialysis and 60 healthy controls(defined as no history of CKD,cardiovascular diseases or neurologic diseases).All subjects underwent evaluations of global cognition(MoCA)and episodic memory(AVLT).Seated and standing blood pressure were measured.Frequency domain heart rate variability were recorded and analyzed.Results:Compared with the healthy controls,patients exhibited rapid blood pressure decline upon standing,with a delayed compensatory rebound following.Correlation analyses showed that orthostatic blood pressure decline was not associated with cognition or memory in the controls,whereas it was correlated significantly to both short recall and delayed recall scores in the patients,but not with global cognition.Multiple stepwise regression analysis revealed that orthostatic blood pressure decline is an independent predictor for memory deficit(both short recall and delayed recall).The association between orthostatic blood pressure decline remained significant after adjusting for heart rate variabilityConclusion:Dialysis patients have overt orthostatic blood pressure decline upon standing,suggesting impaired cardiovascular reactivity.Orthostatic blood pressure decline is associated independently with memory test scores in a reverse fashion in hemodialysis patients and this association remained significant even after adjusting for heart rate variability,suggesting that orthostatic blood pressure decline induce memory deficit directly,possibly through reduced cerebral blood flow.Our findings provide new evidence for understanding the development of memory deficit in hemodialysis patients.Orthostatic blood pressure can be a potential target for preserving memory in patients on maintenance hemodialysis.