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

Miwa, Kaori; Tanaka, Makiko; Okazaki, Shuhei; Furukado, Shigetaka; Yagita, Yoshiki; Sakaguchi, Manabu; Mochizuki, Hideki; Kitagawa, Kazuo

doi:10.1212/wnl.0000000000000251

Cited by 94 publications

(104 citation statements)

References 29 publications

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“…Further, the association of global CI with WMH and cerebral atrophy was independent of CVD history and CVD risk factors for the whole CKD group. These findings might be supported by previous studies indicating that CKD, per se, contributes to cognitive decline [36], independent of ischemic cerebral lesions [35], and that HD is associated with CI, independent of CVD risk factors, SVI, and brain atrophy [37]. Indeed, white matter lesions, which were shown to be a strong predictor of general CI in our study, could be present not only in stroke but also in multiple sclerosis [38], pyridoxine deficiency, and cerebral metabolic disturbances in CKD patients [18].…”

Section: Discussionsupporting

confidence: 83%

Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease

et al. 2016

Kidney Blood Press Res

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Background/Aims: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Methods: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate). Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. Results: Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64), 1.67 (1.09-2.57), and 2.49 (1.07-5.77), respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39). Conclusion: Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients.

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Section: Discussionsupporting

confidence: 83%

Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease

et al. 2016

Kidney Blood Press Res

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“…7 A recent longitudinal study in 600 patients with vascular risk factors found that CKD was related to all-cause dementia independent from vascular risk factors and baseline cerebral small vessel disease. 54 These findings suggest that vascular damage is not the only possible explanation of the association.…”

Section: Continuedmentioning

confidence: 96%

Dementia risk in renal dysfunction

et al. 2017

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Objective: Renal dysfunction has been linked with increased risk for cognitive impairment and dementia, but studies are conflicting. For that reason, the aim of the present systematic review and meta-analysis is to summarize the best available evidence on the prospective association between potential markers of renal dysfunction and development of cognitive impairment or dementia.Methods: Medline, Embase, and Cochrane Database of Systematic Reviews were searched for potential publications until August 1, 2016. Studies were eligible if they fulfilled the following criteria: population-based study, prospective design, $100 participants, aged $45 years, $1 year follow-up, and cognition/dementia outcomes. Where appropriate, random effects meta-analyses were conducted yielding pooled odds ratios (OR) and 95% confidence intervals (CI).Results: Twenty-two out of 8,494 abstracts fulfilled the eligibility criteria. Sufficient evidence was found for albuminuria, mixed results for estimated glomerular filtration rate (eGFR), insufficient support for cystatin C, and tentative evidence for serum creatinine and creatinine clearance. Meta-analyses of 5 studies representing 27,805 persons showed a 35% increased risk of cognitive impairment or dementia in those with albuminuria (OR 1.35, 95% CI 1.06-1.73, p 5 0.015), whereas eGFR ,60 mL/min/1.73 m 2 showed no significant association (OR 1.28, 95% CI 0.99-1.65, p 5 0.063). No meta-analyses could be done for serum creatinine, creatinine clearance, or cystatin C. Conclusions:The overall evidence for an association between renal dysfunction and cognitive impairment or dementia is modest. Evidence suggests that albuminuria is associated with higher odds of developing cognitive impairment or dementia. Renal dysfunction has been considered a candidate risk factor for cognitive impairment and dementia.1-3 The kidneys and the brain, both being end organs, are susceptible to vascular damage due to broadly similar anatomic and hemodynamic features. 4 Chronic kidney disease (CKD) and dementia share a similar risk factor profile including hypertension, diabetes mellitus, or hyperlipidemia, and in both conditions a high prevalence of small vessel disease, silent brain infarcts, white matter pathology, and microbleeds was reported.2,3,5-8 Hence, several pathways may underlie the association between CKD and cognitive impairment, including shared vascular factors or a direct neurotoxic effect of uremia. 2,9 Worldwide, the number of people with dementia has increased.

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“…59 Alteration in memory function that is suggestive of an Alzheimertype dementia can occur in CKD, but the cognitive changes in this condition typically indicate a combination of neurodegenerative dementia, such as Alzheimer disease and vascular dementia. 60 Even in the absence of overt neurological changes, cognitive impairment can be detected in patients with CKD through the use of psychometric tests. 61 Such tests include the Kidney Disease Quality of Life, 62 MiniMental Status Examination, 63 the Modified Mini-Mental State Exam, 64 the 6-Item Screener, 65 St Louis University Mental Test, 66 and the Montreal Cognitive Assessment.…”

Section: Cognitive Testing In Patients With Ckdmentioning

confidence: 99%

Kidney–brain crosstalk in the acute and chronic setting

et al. 2015

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Patients with kidney disease often exhibit multiple organ dysfunction that is caused, in part, by marked connectivity between the kidney and other organs and tissues. Substantial crosstalk occurs between the kidney and the brain, as indicated by the frequent presentation of neurological disorders, such as cerebrovascular disease, cognitive impairment, and neuropathy during the natural history of chronic kidney disease. The underlying pathophysiology of such comorbid neurological disorders in kidney disease is governed by shared anatomic and vasoregulatory systems and humoral and non-humoral bidirectional pathways that affect both the kidney and the brain. During acute kidney injury, the brain and kidney might interact through the amplification of cytokine-induced damage, extravasation of leukocytes, oxidative stress, and dysregulation of sodium, potassium, and water channels. The advent of dialysis and renal transplantation programmes has led to a reduction in the rate of neurological complications associated with uraemia, but a new set of complications have arisen as a consequence of the effects of dialysis on the central nervous system over the short and long term. This Review discusses the clinical complications of acute and chronic renal failure from a neurologic perspective, and highlights current understanding of the underlying pathophysiologies.

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

Abstract: 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.

Cited by 94 publications

References 29 publications

Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease

Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease

Dementia risk in renal dysfunction

Kidney–brain crosstalk in the acute and chronic setting

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