Research Article| Volume 26, ISSUE 2, P420-424, February 2017

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Chronic Kidney Disease and Subclinical Brain Infarction Increase the Risk of Vascular Cognitive Impairment: The Sefuri Study

      Background and Purpose

      The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment.


      We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects.


      Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (β = −.10, P = .027, and β = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (β = −.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (β = −.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant.


      Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects.

      Key Words

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        • Etgen T.
        • Chonchol M.
        • Förstl H.
        • et al.
        Chronic kidney disease and cognitive impairment: a systematic review and meta-analysis.
        Am J Nephrol. 2012; 35: 474-482
        • Hailpern S.M.
        • Melamed M.L.
        • Cohen H.W.
        • et al.
        Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III).
        J Am Soc Nephrol. 2007; 18: 2205-2213
        • Elias M.F.
        • Elias P.K.
        • Seliger S.L.
        • et al.
        Chronic kidney disease, creatinine and cognitive functioning.
        Nephrol Dial Transplant. 2009; 24: 2446-2452
        • Buchman A.S.
        • Tanne D.
        • Boyle P.A.
        • et al.
        Kidney function is associated with the rate of cognitive decline in the elderly.
        Neurology. 2006; 73: 920-927
        • Yaffe K.
        • Ackerson L.
        • Kurella Tamura M.
        • et al.
        Chronic kidney disease and cognitive function in older adults: findings from the chronic renal insufficiency cohort cognitive study.
        J Am Geriatr Soc. 2010; 58: 338-345
        • Davey A.
        • Elias M.F.
        • Robbins M.A.
        • et al.
        Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory.
        Nephrol Dial Transplant. 2013; 28: 1810-1819
        • Silverwood R.J.
        • Richards M.
        • Pierce M.
        • et al.
        NSHD scientific and data collection teams. Cognitive and kidney function: results from a British birth cohort reaching retirement age.
        PLoS ONE. 2014; 9: e86743
        • Darsie B.
        • Shlipak M.G.
        • Sarnak M.J.
        • et al.
        Kidney function and cognitive health in older adults: the Cardiovascular Health Study.
        Am J Epidemiol. 2014; 180: 68-75
        • Yaffe K.
        • Kurella-Tamura M.
        • Ackerson L.
        • et al.
        Higher levels of cystatin C are associated with worse cognitive function in older adults with chronic kidney disease: the chronic renal insufficiency cohort cognitive study.
        J Am Geriatr Soc. 2014; 62: 1623-1629
        • Zammit A.R.
        • Katz M.J.
        • Lai J.Y.
        • et al.
        Association between renal function and cognitive ability domains in the Einstein aging study: a cross-sectional analysis.
        J Gerontol A Biol Sci Med Sci. 2015; 70: 764-770
        • Martens R.J.
        • Kooman J.P.
        • Stehouwer C.D.
        • et al.
        Estimated GFR, albuminuria, and cognitive performance: the Maastricht study.
        Am J Kidney Dis. 2016; (Epub ahead of print)
        • Bugnicourt J.M.
        • Godefroy O.
        • Chillon J.M.
        • et al.
        Cognitive disorders and dementia in CKD: the neglected kidney-brain axis.
        J Am Soc Nephrol. 2013; 24: 353-363
        • Toyoda K.
        • Ninomiya T.
        Stroke and cerebrovascular diseases in patients with chronic kidney disease.
        Lancet Neurol. 2014; 13: 823-833
        • Yao H.
        • Takashima Y.
        • Hashimoto M.
        • et al.
        Subclinical cerebral abnormalities in chronic kidney disease.
        Contrib Nephrol. 2013; 179: 24-34
        • Liu Y.
        • Lv P.
        • Jin H.
        • et al.
        Association between low estimated glomerular filtration rate and risk of cerebral small-vessel diseases: a meta-analysis.
        J Stroke Cerebrovasc Dis. 2016; 25: 710-716
        • Yao H.
        • Miwa Y.
        • Takashima Y.
        • et al.
        Chronic kidney disease and subclinical lacunar infarction are independently associated with frontal lobe dysfunction in community-dwelling elderly subjects: the Sefuri brain MRI study.
        Hypertens Res. 2011; 34: 1023-1028
        • Seliger S.L.
        • Siscovick D.S.
        • Stehman-Breen C.O.
        • et al.
        Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.
        J Am Soc Nephrol. 2004; 15: 1904-1911
        • Miwa K.
        • Tanaka M.
        • Okazaki S.
        • et al.
        Chronic kidney disease is associated with dementia independent of cerebral small-vessel disease.
        Neurology. 2014; 82: 1051-1057
        • Umemura T.
        • Kawamura T.
        • Umegaki H.
        • et al.
        Association of chronic kidney disease and cerebral small vessel disease with cognitive impairment in elderly patients with type 2 diabetes.
        Dement Geriatr Cogn Dis Extra. 2013; 3: 212-222
        • Haenlein M.
        • Kaplan A.M.
        A beginner's guide to partial least squares analysis.
        Understand Stat. 2004; 3: 283-297
        • Yao H.
        • Takashima Y.
        • Araki Y.
        • et al.
        Leisure-time physical inactivity associated with vascular depression or apathy in community-dwelling elderly subjects: the Sefuri study.
        J Stroke Cerebrovasc Dis. 2015; 24: 2625-2631
        • Matsuo S.
        • Imai E.
        • Horio M.
        • et al.
        Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan.
        Am J Kidney Dis. 2009; 53: 982-992
        • Levey A.S.
        • Coresh J.
        • Balk E.
        • et al.
        National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
        Ann Intern Med. 2003; 139: 137-147
        • MacLeod C.M.
        Half a century of research on the Stroop effect: an integrative review.
        Psychol Bull. 1991; 109: 163-203
        • Sasaki M.
        • Hirai T.
        • Taoka T.
        • et al.
        Discriminating between silent cerebral infarction and deep white matter hyperintensity using combinations of three types of magnetic resonance images: a multicenter observer performance study.
        Neuroradiology. 2008; 50: 753-758
        • Wardlaw J.M.
        • Smith E.E.
        • Biessels G.J.
        • et al.
        STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.
        Lancet Neurol. 2013; 12: 822-838
        • Fazekas F.
        • Kleinert R.
        • Offenbacher H.
        • et al.
        Pathologic correlates of incidental MRI white matter signal hyperintensities.
        Neurology. 1993; 43: 1683-1689
        • Reed B.R.
        • Mungas D.M.
        • Kramer J.H.
        • et al.
        Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease.
        Brain. 2007; 130: 731-739
        • Ito S.
        • Nagasawa T.
        • Abe M.
        • et al.
        Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk.
        Hypertens Res. 2009; 32: 115-121
        • Toyoda G.
        • Bokura H.
        • Mitaki S.
        • et al.
        Association of mild kidney dysfunction with silent brain lesions in neurologically normal subjects.
        Cerebrovasc Dis Extra. 2015; 5: 22-27
        • Tsuruya K.
        • Yoshida H.
        • Haruyama N.
        • et al.
        Clinical significance of fronto-temporal gray matter atrophy in executive dysfunction in patients with chronic kidney disease: the VCOHP study.
        PLoS ONE. 2015; 10 (e0143706)
        • Gouw A.A.
        • Seewann A.
        • van der Flier W.M.
        • et al.
        Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations.
        J Neurol Neurosurg Psychiatry. 2011; 82: 126-135
        • Smith E.E.
        • Schneider J.A.
        • Wardlaw J.M.
        • et al.
        Cerebral microinfarcts: the invisible lesions.
        Lancet Neurol. 2012; 11: 272-282