Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT)

Weiner, Daniel E.; Gaussoin, Sarah A.; Nord, John; Auchus, Alexander P.; Chelune, Gordon J.; Chonchol, Michel; Coker, Laura H.; Haley, William E.; Killeen, Anthony A.; Kimmel, Paul L.; Lerner, Alan J.; Oparil, Suzanne; Saklayen, Mohammad G.; Slinin, Yelena; Wright, Clinton B.; Williamson, Jeff D.; Tamura, Manjula Kurella

doi:10.1053/j.ajkd.2017.04.021

Cited by 67 publications

(50 citation statements)

References 42 publications

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“…38,39 There was no effect of antihypertensive treatment on cognitive decline in those with cerebrovascular disease in either the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) 40 or Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) 41 trial, and there was no effect of intense BP control on cognition in those with diabetes mellitus. 42 Results of the Systolic Blood Pressure Intervention Trial (SPRINT) and Memory and Cognition in Decreased Hypertension (MIND) study 43 will provide further insights into the effect of intensive BP lowering on cognition. Our results indicating an effect of combined BP and lipid lowering in the prevention of cognitive decline in those with the highest initial BP levels suggest that those at highest cardiovascular risk may benefit.…”

Section: Discussionmentioning

confidence: 99%

Effects of blood pressure and lipid lowering on cognition

et al. 2019

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ObjectiveTo assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.MethodsThe Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.ResultsCognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was −0.91 (95% confidence interval [CI] −2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, −0.54 (95% CI −1.88 to 0.80) for rosuvastatin compared with placebo, and −1.43 (95% CI −3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.ConclusionsLong-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people.ClinicalTrials.gov identifierNCT00468923.Classification of evidenceThis study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.

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confidence: 99%

Effects of blood pressure and lipid lowering on cognition

et al. 2019

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“…Mechanisms include accumulation of uraemic toxins, endothelial dysfunction, vascular calcification, klotho deficiency and hypertension with associated dramatically accelerated small vessel cerebrovascular disease . Cognitive impairment and white matter abnormalities are independently associated with renal impairment in a dose‐related fashion . In addition, albuminuria is associated with cerebral white matter abnormalities and cognitive impairment independently of eGFR .…”

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confidence: 99%

“…9 Cognitive impairment and white matter abnormalities are independently associated with renal impairment in a dose-related fashion. [10][11][12][13] In addition, albuminuria is associated with cerebral white matter abnormalities and cognitive impairment independently of eGFR. 12,14 Conversely, some investigators have found that hemodialysis can be associated with improved cognitive performance, presumably by virtue of clearing uraemic toxins.…”

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confidence: 99%

“…[10][11][12][13] In addition, albuminuria is associated with cerebral white matter abnormalities and cognitive impairment independently of eGFR. 12,14 Conversely, some investigators have found that hemodialysis can be associated with improved cognitive performance, presumably by virtue of clearing uraemic toxins. 15 Given this background, it is extremely difficult to isolate the impact of ischemic, osmotic and inflammatory insults derived from hemodialysis itself.…”

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Cerebral ischemia during hemodialysis—finding the signal in the noise

MacEwen

Watkinson

Tarassenko

et al. 2018

Seminars in Dialysis

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Hemodialysis patients have multiple risk factors for small vessel cerebrovascular disease and cognitive dysfunction. Hemodialysis itself may cause clinically significant neurological injury through repetitive cerebral ischemia. However, supporting evidence to date consists of epidemiological associations, expert opinion, and small, single-centre studies of variable methodological quality. Isolating the impact of intra-dialytic hemodynamic instability from underlying renal and vascular disease on clinically relevant functional outcomes would require very large, controlled studies, given the heterogeneity and confounding comorbidities of the population, and the complex relationship between blood pressure and cerebral oxygen delivery. There has been an increase in complementary physiological studies looking directly at intra-dialytic cerebral oxygen balance, which have provided supporting evidence for the occurrence of cerebral ischemia, often independently of hemodynamics. Data suggesting a relationship between these measures of oxygen balance and functional outcomes is only hypothesis-generating at this stage. We advocate the testing of interventions that aim to reduce intra-dialytic cerebral hypoxia (rather than hypotension) in sufficiently powered studies, followed by correlation with validated, longitudinal assessment of clinically relevant neurological damage.

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“…In the same cohort of maintenance HD patients reported in this manuscript, we previously demonstrated an association between lower DBP and worse cognitive performance; however, we found that this relationship was attenuated and became nonsignificant when adjusting for demographics and comorbidity [12]. There are even less data on the impact of different BP goals on cognitive function in CKD patients, and longitudinal data on cognitive function from the recently completed SBP Intervention Trial are eagerly awaited [33].…”

Section: Discussionmentioning

confidence: 61%

Blood Pressure and Cognitive Decline in Prevalent Hemodialysis Patients

Drew¹,

Tighiouart²,

Duncan³

et al. 2019

Am J Nephrol

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Background: Hypertension is associated with cognitive decline in the general population. It is unclear what impact blood pressure (BP) has on cognitive decline in patients receiving maintenance hemodialysis (HD). Methods: Using a longitudinal cohort of 314 prevalent HD patients without dementia at baseline, we examined the association of predialysis systolic BP (SBP) and diastolic BP (DBP), pulse pressure, and intradialytic SBP change (pre minus post), averaged for a month, with cognitive decline. Cognitive function was determined by a neurocognitive battery, administered yearly. Individual cognitive test results were reduced into 2 domain scores using principal components analysis (by definition mean of 0 and SD of 1), representing memory and executive function. Joint models, allowing for characterization of cognitive score slopes and including adjustment for potential confounders, were utilized to account for competing risks from death, dropout, or kidney transplantation. Results: Mean age was 62 years; 54% were men, 23% were black, and 90% had at least a high school education. During median follow-up of 2.1 years (25th–75th: 1.0–4.5), 191 had at least one follow-up test, 148 died, and 43 received kidney transplants. Low predialysis DBP and high pulse pressure were both associated with steeper executive function decline (each 10 mm Hg lower DBP = –0.03 SD [–0.01 to –0.05] per year steeper decline) in executive function (each 10 mm Hg higher pulse pressure = –0.03 SD [–0.06 to –0.01] steeper decline) but not for memory function. SBP and intradialytic change were not associated with steeper decline for either memory or executive function. Conclusions: No relationship was seen between SBP or intradialytic change in BP with cognitive decline. In prevalent HD patients, lower predialysis DBP and wider predialysis pulse pressure are associated with steeper cognitive decline in executive function but not memory.

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Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT)

Cited by 67 publications

References 42 publications

Effects of blood pressure and lipid lowering on cognition

Effects of blood pressure and lipid lowering on cognition

Cerebral ischemia during hemodialysis—finding the signal in the noise

Blood Pressure and Cognitive Decline in Prevalent Hemodialysis Patients

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