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March 25, 2014; 82 (12) Article

Chronic kidney disease is associated with dementia independent of cerebral small-vessel disease

Kaori Miwa, Makiko Tanaka, Shuhei Okazaki, Shigetaka Furukado, Yoshiki Yagita, Manabu Sakaguchi, Hideki Mochizuki, Kazuo Kitagawa
First published February 19, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000251
Kaori Miwa
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Makiko Tanaka
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Shuhei Okazaki
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Shigetaka Furukado
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Yoshiki Yagita
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Manabu Sakaguchi
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Hideki Mochizuki
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Kazuo Kitagawa
From the Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Japan.
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Citation
Chronic kidney disease is associated with dementia independent of cerebral small-vessel disease
Kaori Miwa, Makiko Tanaka, Shuhei Okazaki, Shigetaka Furukado, Yoshiki Yagita, Manabu Sakaguchi, Hideki Mochizuki, Kazuo Kitagawa
Neurology Mar 2014, 82 (12) 1051-1057; DOI: 10.1212/WNL.0000000000000251

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Abstract

Objective: To determine whether chronic kidney disease (CKD) is associated with incident dementia independent of cerebral small-vessel disease (SVD) in patients with vascular risk factors.

Methods: Using data from a Japanese cohort of participants with vascular risk factors in an ongoing observational study from 2001, we evaluated the association between CKD at baseline and incident dementia. Baseline brain MRI was used to determine SVD (lacunar infarction, white matter hyperintensities), medial-temporal atrophy, and subcortical atrophy. Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE ε4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings.

Results: Of the 600 subjects (mean age 68 ± 8.3 years, 57% male, 12.8 ± 2.6 years of education; CKD: 29%), 50 patients with incident dementia (Alzheimer disease: 24; vascular dementia: 18; mixed-type dementia: 5; other types: 3) were diagnosed during the median 7.5-year follow-up. CKD at baseline was associated with an increased risk of all-cause dementia in models adjusted for age, sex, educational level, and APOE ε4 allele. The associations of CKD at baseline remained significant even after additional adjusting for MRI findings and confounding variables (hazard ratio: 1.96 [1.08–3.58], p = 0.026).

Conclusions: CKD is independently related to the risk of all-cause dementia in patients with vascular risk factors. Our results reinforce the hypothesis that CKD exerts deleterious effects on dementia incidence.

GLOSSARY

AD=
Alzheimer disease;
BCR=
bicaudate ratio;
CDR=
Clinical Dementia Rating;
CKD=
chronic kidney disease;
DSM-III-R=
Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised;
eGFR=
estimated glomerular filtration rate;
LI=
lacunar infarction;
MMSE=
Mini-Mental State Examination;
OSACA2=
Osaka Follow-up Study for Carotid Atherosclerosis, Part 2;
PVH=
periventricular hyperintensity;
SVD=
small-vessel disease;
VaD=
vascular dementia;
WMH=
white matter hyperintensity

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received August 29, 2013.
  • Accepted in final form December 12, 2013.
  • © 2014 American Academy of Neurology
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