Hypertens Res. 2014 Jul;37(7):636-41.

The effects of blood pressure and the renin-angiotensin-aldosterone system on regional cerebral blood flow and cognitive impairment in dialysis patients.

Kobayashi S1, Mochida Y1, Ishioka K1, Oka M1, Maesato K1, Moriya H1, Hidaka S1, Ohtake T1.
  • 1Department of Nephrology, Immunology and Vascular Medicine, Shonan Kamakura General Hospital, Kamakura, Japan.



Cognitive dysfunction is prevalent in chronic kidney disease patients. Little is known about the relationship between the regional cerebral blood flow (rCBF) and cognitive function in hemodialysis (HD) patients. We used quantitative single-photon emission-computed tomography (SPECT) to determine whether rCBF decreased in these patients. Fifty-four consecutive HD patients who were able to visit the hospital unassisted and had no history of stroke underwent cognitive assessment based on the Mini Mental State Examination (MMSE). Using quantitative image-analysis software, the SPECT imaging data were used to compare rCBF in HD patients and age-matched healthy controls. Thirty-four patients (63%) had MMSE scores ⩾28 (non-dementia). Regarding the extent of decreased rCBF in HD patients compared with rCBF in normal control patients, SPECT demonstrated significant rCBF decreases in all patients. rCBF in the perfusion area of the middle cerebral artery was significantly more decreased than in other areas. Multiple logistic regression analysis demonstrated that the presence or absence of a previous history of percutaneous coronary intervention, drug therapy with angiotensin II receptor antagonists and diastolic blood pressure (DBP) were independent risk factors for the extent of decreased rCBF. Regarding the severity of decreased rCBF, stepwise multiple regression analysis indicated that HD duration and systolic blood pressure (mm Hg) were chosen. In conclusion, rCBF decreased in all HD patients studied, irrespective of their clinical symptoms or MMSE scores. Blood pressure was an independent risk factor affecting the extent of decreased rCBF.

PMID: 24694648



Regional cerebral blood flow and cognitive impairment in dialysis patients ~ a role of blood pressure and renin-angiotensin-aldosterone system. 

Shuzo Kobayashi, Yasuhiro Mochida, Kunihiro Ishioka, Machiko Oka, Kyoko Maesato, Hidekazu Moriya, Sumi Hidaka, and Takayasu Ohtake

Department of Nephrology, Immunology, and Vascular Medicine, Shonan Kamakura General Hospital.

1370-1 Okamoto, Kamakura

247-8533, Japan



Cognitive dysfunction becomes worldwide problem to be solved in developed countries. It is well known that the prevalence of cognitive dysfunction is higher in hemodialysis patients (1). Economic burden makes it serious matter for not only hemodialysis patients but also all people.

Number of patients with hemodialysis is increasing, and the age at the initiation of dialysis also is getting older. These facts apparently affect the prevalence of cognitive dysfunction.

However, it is also easily understood why cognitive dysfunction would occur in CKD patients in terms of the pathophysiology in which the patients mostly have chronic inflammation and atherosclerotic vascular events. Cognitive dysfunction consists of two main pathophysiology, one is Alzheimer dementia, and the other is vascular dementia. Although the study of Alzheimer dementia progresses, vascular dementia also should be focused on because of asymptomatic lacunar infarction in which as the pathophysiology, microcirculatory impairment in strain vessels in mid-cerebral arteries plays an important role, is more prevalent (2) prior to the initiation of dialysis.

The results showing significant decrease in cerebral blood flow, irrespective of MMSE score in all patients studied, were a great shock to us. Stepwise multiple regression analysis (R=0.501 R2=0.224 P=0.0003) shows:

Maximum severity = 0.002 x HD Duration + 0.016 SBP + 0.221



  1. Murray AM, Tupper DE, Knopman DS, et al. Cognitive impairment in hemodialysis patients is common. Neurology 2006; 67: 216-223.
  2. Kobayashi S, Ikeda T, Moriya H, Ohtake T, Kumagai H. Asymptomatic cerebral lacunae in patients with chronic kidney disease. Am J Kidney Dis 2004; 44: 35-41



Figure 1. The maximum extent of decreased rCBF more than 2 of Z-score in each patient is ranked. Vertical shows % of extent in area. Horizontal line shows all patients from No1. to No.54 studied. Extent is expressed as the rate of the total coordinates with significantly reduced Z-score in territory area (anterior, middle, and posterior cerebral artery) (extent). More than two of Z-score was defined as decreased rCBF, which corresponds to a decrease more than 2 standard deviation (SD) of average values compared with those in reference.



fig 2

Figure 2 Representative pattern of decreased regional cerebral blood flow (rCBF) is shown. From black to red, rCBF is decreasing according to area in brain. In cingulate gyrus, precuneus, and frontal lobe, rCBF decreases more evident.



Table 1 Univariate regression analysis of maximum severity


Stepwise multiple regression analysis: R=0.501 R2=0.224 P=0.0003

Maximum Severity = 0.002 x HD Duration + 0.016 SBP + 0.221





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