Up Front MattersBrief Reviews

Cognitive Disorders and Dementia in CKD: The Neglected Kidney-Brain Axis

Jean-Marc Bugnicourt, Olivier Godefroy, Jean-Marc Chillon, Gabriel Choukroun and Ziad A. Massy
JASN March 2013, 24 (3) 353-363; DOI: https://doi.org/10.1681/ASN.2012050536

Abstract

Epidemiologic data suggest that individuals at all stages of CKD have a higher risk of developing cognitive disorders and dementia. This risk is generally explained by the high prevalence of both symptomatic and subclinical ischemic cerebrovascular lesions. However, other potential mechanisms, including direct neuronal injury by uremic toxins, could also be involved, especially in the absence of obvious cerebrovascular disease. We discuss the prevalence and characteristics of cognitive disorders and dementia in patients with CKD, brain imaging findings, and traditional and nontraditional risk factors. Understanding the pathophysiologic interactions between renal impairment and brain function is important in order to minimize the risk for future cognitive impairment.

CKD is a substantial public health problem. On the basis of the French national renal data system, it has been estimated that between 1.75 and 2.5 million people in France have CKD1 and that nearly 40,000 of the latter are undergoing dialysis. In the United States, similar results have been observed: Almost 8% of the population has CKD and 571,000 patients receive treatment for ESRD.2 Although the incidence of CKD is increasing in all age groups, this is particularly true in the elderly.3 Older adults are at a greater risk of developing cognitive disorders and dementia, and a major determinant of the quality of life in the elderly is the level of cognitive function.4 Recent data in this regard suggest that individuals at all stages of CKD may have a higher risk of developing dementia and cognitive impairment than those without CKD.5–7 Given the increase in life expectancy and the aging of the population in industrialized countries, the cognitive disorder burden associated with CKD is expected to worsen.

Prevalence and Characteristics of Cognitive Impairment in CKD

Patients with Stage 5 CKD

In hemodialysis patients, the prevalence of cognitive impairment has been estimated at 30%–60%6,8–10—at least twice the values observed in age-matched controls.11 Table 1 summarizes the characteristics of the main studies assessing the prevalence of cognitive impairment in hemodialysis patients. One main limitation of these early studies concerns the cognitive assessment. Initially, cognitive impairment was based on short screening tests, such as the Mini-Mental State Examination (MMSE)12 and the 3MS (an extension of the MMSE with four additional subtests and a maximum score of 100 points instead of 30 points). The limited sensitivity of short screening tests of cognitive impairment in general and vascular cognitive impairment in particular13 probably led to an underestimation of the prevalence of cognitive impairment in CKD. In a cross-sectional study, Murray et al. compared 338 hemodialysis patients age 55 years and older with age-matched controls.14 Although only 3% of the patients had a documented history of cognitive impairment, further neuropsychological testing showed that the true prevalence of mild to severe cognitive impairment was as high as 87%. This finding was emphasized by another study by Kurella et al.15 According to data collected from a large, international sample of hemodialysis patients with a mean age of 60, only 4% of patients had a previously documented diagnosis of dementia. This value is lower than the prevalence reported in the general population age 65 or older.16,17

View this table:
Table 1.

Prevalence of cognitive disorders and dementia in hemodialysis patients

Another important limitation in the interpretation of study data concerns study design, which differs from one study to the other. Some investigators did not report the proportion of nonevaluated patients or provide information on confounding factors, such as sociocultural demographic characteristics, the presence of depressive syndrome, vascular risk factors, and prior cerebrovascular events (such as stroke).

Lastly, most of the cognitive tests were administered during a hemodialysis session. Recently, Murray et al. showed that global cognitive function varies significantly over the course of the dialysis session; performance is worst during the session itself and best shortly before the session or on the day after.18 In patients undergoing peritoneal dialysis, the few available data suggest that the prevalence of cognitive impairment might be lower than in hemodialysis patients.19,20 However, this apparent discrepancy may reflect selection bias (because the dialysis procedure will depend on the patients’ characteristics and thus cognitive function before the introduction of dialysis21) rather than the procedure’s characteristics per se.

Patients with Mild to Moderate CKD

Cognitive impairment in CKD is not limited to patients with stage 5 CKD. Several cross-sectional studies have suggested its occurrence in earlier stages of kidney disease (Table 2). Thus, estimated GFR (eGFR) was inversely related to global performance in global cognitive function tests.6,22,23 Yaffe et al. confirmed this observation by applying a more detailed battery of neuropsychological tests.24 They reported that an inverse relation between eGFR and global cognitive function was observed for most cognitive domains, but the pattern of cognitive impairment differed from one CKD subgroup to another. Patients with advanced CKD (defined as eGFR<30 ml/min per 1.73 m2) were more likely to have cognitive impairment as revealed by tests evaluating global cognition, naming, attention, executive function, and delayed memory, but not tests assessing fluency and immediate memory, compared with patients with mild or moderate CKD (defined as an eGFR 45–59 ml/min per 1.73 m2).

View this table:
Table 2.

Main studies of association between mild to moderate CKD and cognitive impairment

The results of longitudinal studies also suggest that CKD is an independent risk factor for cognitive impairment because lower eGFR at study enrollment is associated with a more rapid rate of cognitive decline.25–28 In the Cardiovascular Health Cognition Study, the first study devoted to this topic, Seliger et al. reported that after adjustment for potential confounders, moderate kidney failure is associated with a 37% increase in the risk for dementia.28 In a population of 3034 community-dwelling older adults, Kurella et al. also showed that CKD, defined as an eGFR<60 ml/min per 1.73 m2, is associated with an increased risk for cognitive impairment. Furthermore, the risk for cognitive impairment in this population varied according to the severity of CKD, suggesting a causal relation.27 This association has been confirmed by other recent studies.25,26

However, two other studies failed to show an association between CKD at baseline and the risk for cognitive decline.29,30 In the first, a prospective, cohort study of 5529 healthy older men, Slinin et al. found an independent association between mild to moderate reductions in kidney function and executive function at baseline but not at the end of the follow-up period.30 Recently, data from the 3C population-based cohort study, which included 7839 patients older than age 65 with 7 years of follow-up and baseline eGFR<60 ml/min per 1.73 m2, were not associated with an increased risk for incident dementia or cognitive decline.29 However, in this latter study, the percentage of participants with CKD was relatively low (12% with a baseline eGFR<60 ml/min per 1.73 m2). Furthermore, the patients had a relatively low cardiovascular risk profile, in line with the low prevalence of CKD. This precludes generalization of the study findings to patient populations with more advanced CKD.

Brain Imaging in CKD Patients

Clinically Evident Stroke and Subclinical Cerebrovascular Disease in CKD Patients

Patients with CKD display a high prevalence of stroke. According to the U.S. Renal Data System, the prevalence is 17% for patients undergoing long-term hemodialysis, 10% for patients with mild to moderate CKD, and 4% in the non-CKD population, after accounting for age, sex, and race.2 A history of stroke doubles the risk for dementia in both CKD and non-CKD populations.2 Furthermore, CKD patients have an increased prevalence of subclinical cerebrovascular disease, with silent brain infarcts (SBIs), cerebral infarcts detected by brain imaging in the absence of clinical symptoms, more white matter lesions (WMLs), and more microbleeds (Figure 1).31

Figure 1.
Figure 1.

Subclinical brain lesions in CKD patients. (A) Axial fluid-attenuated inversion recovery magnetic resonance image showing silent brain lacunar infarct (arrow). (B) Axial gradient-echo magnetic resonance imaging sequence showing multiple microbleeds (small foci of hypointensity, arrows) located in the right cerebral hemisphere. Moderate (C) and severe (D) white-matter lesions in the centrum ovale.

Brain Lesions in CKD Patients

Brain lesions in CKD patients were first described in computed tomography–based studies (Table 3). More than 30 years ago, Passer et al. reported a high prevalence of cerebral atrophy in patients undergoing long-term hemodialysis.32 It was subsequently shown in such patients that the lesions were prominent in the frontal lobes and were correlated with the duration of hemodialysis.33,34 Other markers or risk factors for potential cerebrovascular disease, such as SBIs, have also been reported. Cusmano and Savazzi showed that 10% of CKD patients, most of whom were undergoing hemodialysis, had SBIs.35 More recently, we found a strong association between eGFR and intracranial artery calcification in patients hospitalized for stroke or nonvascular neurologic disorders.36 This is not surprising, given that CKD is associated with an accelerated, active vascular calcification process.37

View this table:
Table 3.

Main brain imaging studies in CKD patients

Magnetic resonance imaging (MRI) has allowed a considerable increase in the rate of detection of subclinical cerebrovascular damage in CKD patients. It has been estimated that approximately half of the patients with advanced CKD stages have SBIs, whereas the prevalence in the general population ranges from 8% to 28%.38 SBIs are associated with an increased risk for stroke, cognitive decline, and incident dementia in CKD patients.39 Furthermore, a small, prospective cohort study showed that SBIs were an independent prognostic factor for the progression of kidney disease in patients with CKD, independently of other established risk factors.40

Likewise, the prevalence of WMLs is high (up to 70%) in both CKD patients and stroke patients.9,41,42 This is not surprising, given that WMLs are thought to be symptomatic of a progressive, irreversible process that follows on from arteriolosclerosis.43 Most cross-sectional, population-based studies show a strong association between eGFR on one hand and white matter volume and WMLs on the other.44–46 Only Martinez-Vea et al. failed to report a statistically significant relationship between vascular nephropathy and WMLs in a multivariate analysis.47 This absence suggests that the elevated number of WMLs in CKD patients is a marker of systemic vascular disease. As with SBIs, WMLs are predictors of an increased incidence of stroke, dementia, and death.48 Other markers strongly associated with cerebral small vessel disease (microbleeds or microhemorrages) have been studied less extensively.

The incidence of cerebral microbleeds is higher in patients undergoing hemodialysis49 and also in patients with a more moderate decrease in renal function.50 In two other studies performed in patients with ischemic stroke, similar associations between chemical markers of CKD and cerebral microbleeds have been observed.51,52 Interestingly, Watanabe also found a high incidence of microbleeds in patients undergoing maintenance hemodialysis but failed to find any correlation between the duration of hemodialysis and the prevalence of microbleeds. The author concluded that the high proportion of patients with microbleeds in this population was caused by other risk factors, possibly arterial hypertension and uremic toxins, rather than maintenance hemodialysis per se.53 However, one must bear in mind that most of the above studies were performed in Asian persons—an ethnic group whose patterns of clinically evident and subclinical cerebrovascular disease greatly differs from that in other populations. This point was recently emphasized by the results of a meta-analysis by Lee et al. in which the presence of low eGFR was a marker for increased risk for stroke, with the highest risk being observed in Asian populations.54

Potential Causes of Cognitive Impairment in Patients with CKD

The Vascular Hypothesis of Cognitive Impairment

Figure 2 presents the possible causes of cognitive impairment in patients with CKD. The brain and the kidneys have many common anatomic and vasoregulatory features; they are low resistance end organs exposed to high-volume blood flow and thus are susceptible to vascular damage.55 Hence, impaired cerebral hemodynamics, as evaluated by transcranial Doppler ultrasonography, may reveal interesting information on the association between altered cerebrovascular hemodynamics and cognitive impairment.56 Indeed, previous transcranial Doppler studies show a positive correlation between hemodynamic impairment and cognitive impairment—suggesting that microvascular damage contributes to the cognitive changes observed in the early stages of dementia.57,58 Additionally, the prevalence of traditional vascular risk factors, such as arterial hypertension, is higher in patients with CKD than in the general population.2 This might explain the association between CKD and cerebrovascular disease because the latter plays the largest role in the pathogenesis of cognitive impairment in CKD patients.

Figure 2.
Figure 2.

Schematic representation of potential causes of cognitive impairment in patients with CKD.

Furthermore, it has been suggested that vascular disease is a more likely cause of cognitive impairment than is Alzheimer’s disease in this population. This hypothesis is supported by recent published data from the 3C study: Faster eGFR decline (>4 ml/min per 1.73 m2 during the first 4-year period of follow-up) was associated with global cognitive decline and incident dementia with a vascular component.29 The contribution of cerebral vascular lesions to cognitive impairment in CKD patients is also supported by the pattern of cognitive disorders; the prominent impairment of executive functions and psychomotor speed resembles the situation in stroke.59 However, the results of a neuropathologic study indicates that patients with small-vessel cerebrovascular disease present broader cognitive impairment, which can also include memory deficits. These findings thus challenge the utility of executive impairment as a diagnostic marker for vascular cognitive impairment or dementia.60

Nontraditional vascular risk factors, such as hyperhomocysteinemia, hypercoagulable states, inflammation, and oxidative stress, have also been linked to cognitive impairment.61 These factors could accelerate the progression of atherosclerosis and vascular endothelial dysfunction, both of which are associated with dementia risk.62,63 Interestingly, elevated homocysteine levels are present in 85% of dialysis patients but only 10% of the general population.64 In a prospective cohort study, plasma homocysteine was an independent risk factor for dementia.65

There are several possible mechanisms through which elevated homocysteine levels may cause cognitive impairment. First, hyperhomocysteinemia has a direct prothrombotic effect on the vascular system and thus may lead to both large- and small-vessel disease.66 Elevated homocysteine levels are also associated with the number of WMLs and progression—possibly through direct endothelial damage or stimulation of an endothelial inflammatory response.65,67,68 Second, hyperhomocysteinemia could impair neuronal pathways because elevated homocysteine has a direct, neurotoxic effect by activating the N-methyl-D-aspartate receptor or by conversion into homocysteic acid, leading to cell death.69 Furthermore, clinical studies show that elevated plasma homocysteine concentrations are associated with an increased risk for Alzheimer disease.70 However, lowering homocysteine levels in dementia patients does not appear to reduce global cognitive decline.71

The Neurodegenerative Hypothesis of Cognitive Impairment

The vascular risk factors and brain abnormalities mentioned above can only partly explain the high frequency of vasculopathy-related cognitive disorders observed in CKD patients. Hence, other disease mechanisms are necessarily involved. First, chronic hypertension and numerous vascular risk factors are associated with an increased risk for Alzheimer disease.72 Conversely, the results of observational studies and clinical trials suggest that antihypertensive drugs may decrease age-related cognitive decline and dementia, although longitudinal studies have provided inconsistent findings.73 In 2001, the Rotterdam study showed that antihypertensive treatment was associated only with a lower risk for vascular dementia.74 However, the Systolic Hypertension in Europe (Syst-Eur) and Syst-Eur 2 trials showed a significant, 50% reduction in the incidence of both vascular and neurodegenerative dementia.75,76 During the past decade, most studies have focused on the observation that beneficial effects of various antihypertensive drugs in preventing cognitive decline and dementia are apparently not correlated with their BP-lowering activity.77

It has been suggested that angiotensin-converting enzyme inhibitors might have deleterious effects on cognition (because they prevent angiotensin-converting enzyme–mediated conversion of Aβ42 into Aβ40, which is less amyloidogenic and less toxic), whereas angiotensin AT1-receptor blockers might exert a protective effect on cognition due to their activation of AT2 and AT4 receptors. Moreover, the accumulation of uremic toxins may cause cerebral endothelial dysfunction and contribute to cognitive disorders in CKD.78 Various uremic toxins have been implicated in the pathogenesis of cognitive impairment.79 DeDeyn et al. reported that cerebrospinal fluid and brain levels of some guanidine compounds, such as creatinine, guanidine, guanidinosuccinic acid, and methylguanidine, are substantially elevated in uremic patients.80 Interestingly, these high toxin concentrations (up to 10-fold higher in CKD patients than in controls) were found in brain regions that play a determinant role in cognition, such as the thalamus, the mammillary bodies, and the cerebral cortex.80 It is well known that these uremic guanidine compounds are neuroexcitatory agents and have convulsant activity in animal studies.81 However, it is still not clear whether uremic toxins are directly responsible for cognitive impairment. The involvement of guanidines in cognitive disorders could also be indirect because it has been shown that these compounds favor an elevation of serum homocysteine.82 Lastly, Yaffe et al. showed that community-resident elderly individuals with elevated levels of cystatin-C (an inhibitor of cysteine proteases that co-localizes with β-amyloid in the brain of patients with Alzheimer disease) had lower cognitive test scores and were more likely to experience a decline in cognitive function during a 7-year follow-up period—even after adjustment for vascular risk factors.83 Despite the absence of brain MRI data, it is possible that cystatin-C has a direct effect on the risk of developing Alzheimer disease.

Conclusion

The pathophysiologic link between brain and kidney injury is strong and complex. The cognitive disorders observed in CKD patients are probably explained by the common susceptibility of brain tissue to vascular injury. Brain MRI should be systematically performed in CKD patients with cognitive impairment because the frequency of both clinically apparent and silent cerebrovascular lesions is strikingly increased compared with that in the general population. In addition to cerebrovascular causes, other potential mechanisms, such as direct neuronal toxicity of the uremic state, could also be involved in CKD patients with cognitive disorders, especially in the absence of obvious cerebrovascular disease. Understanding the pathophysiologic interactions between renal impairment and brain function in CKD patients is important in order to minimize the risk for future cognitive impairment. Attempt to reach this goal would benefit from collaboration between neurologists and nephrologists.

Disclosures.

None

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

References

  1. ↵
    1. Couchoud C,
    2. Lassalle M,
    3. Stengel B,
    4. Jacquelinet C
    : [Renal Epidemiology and Information Network: 2006 annual report]. Nephrol Ther 4[Suppl 2]: S53–S167, 2008pmid:19058350
    OpenUrlCrossRefPubMed
  2. ↵
    1. Collins AJ,
    2. Foley RN,
    3. Herzog C,
    4. Chavers B,
    5. Gilbertson D,
    6. Ishani A,
    7. Kasiske B,
    8. Liu J,
    9. Mau LW,
    10. McBean M,
    11. Murray A,
    12. St Peter W,
    13. Guo H,
    14. Gustafson S,
    15. Li Q,
    16. Li S,
    17. Li S,
    18. Peng Y,
    19. Qiu Y,
    20. Roberts T,
    21. Skeans M,
    22. Snyder J,
    23. Solid C,
    24. Wang C,
    25. Weinhandl E,
    26. Zaun D,
    27. Arko C,
    28. Chen SC,
    29. Dalleska F,
    30. Daniels F,
    31. Dunning S,
    32. Ebben J,
    33. Frazier E,
    34. Hanzlik C,
    35. Johnson R,
    36. Sheets D,
    37. Wang X,
    38. Forrest B,
    39. Constantini E,
    40. Everson S,
    41. Eggers P,
    42. Agodoa L
    : US Renal Data System 2010 Annual Data Report. Am J Kidney Dis 57[Suppl 1]: A8, e1–e526, 2011pmid:21184928
    OpenUrlPubMed
  3. ↵
    Collins AJ, Kasiske B, Herzog C, Chavers B, Foley R, Gilbertson D, Grimm R, Liu J, Louis T, Manning W, McBean M, Murray A, St Peter W, Xue J, Fan Q, Guo H, Li Q, Li S, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zhang R, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Berrini D, Constantini E, Everson S, Eggers P, Agodoa L: Excerpts from the United States Renal Data System 2006 annual data report. Am J Kidney Dis 49: A6–7, S1–296, 2007.
  4. ↵
    1. Kurella M,
    2. Luan J,
    3. Yaffe K,
    4. Chertow GM
    : Validation of the Kidney Disease Quality of Life (KDQOL) cognitive function subscale. Kidney Int 66: 2361–2367, 2004pmid:15569327
    OpenUrlCrossRefPubMed
  5. ↵
    1. Elias MF,
    2. Elias PK,
    3. Seliger SL,
    4. Narsipur SS,
    5. Dore GA,
    6. Robbins MA
    : Chronic kidney disease, creatinine and cognitive functioning. Nephrol Dial Transplant 24: 2446–2452, 2009pmid:19297357
    OpenUrlCrossRefPubMed
  6. ↵
    1. Kurella M,
    2. Chertow GM,
    3. Luan J,
    4. Yaffe K
    : Cognitive impairment in chronic kidney disease. J Am Geriatr Soc 52: 1863–1869, 2004pmid:15507063
    OpenUrlCrossRefPubMed
  7. ↵
    1. Madan P,
    2. Kalra OP,
    3. Agarwal S,
    4. Tandon OP
    : Cognitive impairment in chronic kidney disease. Nephrol Dial Transplant 22: 440–444, 2007pmid:17023495
    OpenUrlCrossRefPubMed
  8. ↵
    1. Antoine V,
    2. Souid M,
    3. André C,
    4. Barthélémy F,
    5. Saint-Jean O
    : [Symptoms and quality of life of hemodialysis patients aged 75 and over]. Nephrologie 25: 89–96, 2004pmid:15185556
    OpenUrlPubMed
  9. ↵
    1. Fazekas G,
    2. Fazekas F,
    3. Schmidt R,
    4. Kapeller P,
    5. Offenbacher H,
    6. Krejs GJ
    : Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. J Neurol Sci 134: 83–88, 1995pmid:8747848
    OpenUrlCrossRefPubMed
  10. ↵
    1. Sehgal AR,
    2. Grey SF,
    3. DeOreo PB,
    4. Whitehouse PJ
    : Prevalence, recognition, and implications of mental impairment among hemodialysis patients. Am J Kidney Dis 30: 41–49, 1997pmid:9214400
    OpenUrlCrossRefPubMed
  11. ↵
    1. Graham JE,
    2. Rockwood K,
    3. Beattie BL,
    4. Eastwood R,
    5. Gauthier S,
    6. Tuokko H,
    7. McDowell I
    : Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 349: 1793–1796, 1997pmid:9269213
    OpenUrlCrossRefPubMed
  12. ↵
    1. Folstein MF,
    2. Folstein SE,
    3. McHugh PR
    : “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189–198, 1975pmid:1202204
    OpenUrlCrossRefPubMed
  13. ↵
    1. Godefroy O,
    2. Fickl A,
    3. Roussel M,
    4. Auribault C,
    5. Bugnicourt JM,
    6. Lamy C,
    7. Canaple S,
    8. Petitnicolas G
    : Is the Montreal Cognitive Assessment superior to the Mini-Mental State Examination to detect poststroke cognitive impairment? A study with neuropsychological evaluation. Stroke 42: 1712–1716, 2011pmid:21474808
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Murray AM,
    2. Tupper DE,
    3. Knopman DS,
    4. Gilbertson DT,
    5. Pederson SL,
    6. Li S,
    7. Smith GE,
    8. Hochhalter AK,
    9. Collins AJ,
    10. Kane RL
    : Cognitive impairment in hemodialysis patients is common. Neurology 67: 216–223, 2006pmid:16864811
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Kurella M,
    2. Mapes DL,
    3. Port FK,
    4. Chertow GM
    Correlates and outcomes of dementia among dialysis patients: The Dialysis Outcomes and Practice Patterns Study. Nephrol Dial Transplant 21: 2543–2548, 2006pmid:16751655
    OpenUrlCrossRefPubMed
  16. ↵
    1. Bachman DL,
    2. Wolf PA,
    3. Linn R,
    4. Knoefel JE,
    5. Cobb J,
    6. Belanger A,
    7. D’Agostino RB,
    8. White LR
    : Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 42: 115–119, 1992pmid:1734291
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Evans DA,
    2. Funkenstein HH,
    3. Albert MS,
    4. Scherr PA,
    5. Cook NR,
    6. Chown MJ,
    7. Hebert LE,
    8. Hennekens CH,
    9. Taylor JO
    : Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 262: 2551–2556, 1989pmid:2810583
    OpenUrlCrossRefPubMed
  18. ↵
    1. Murray AM,
    2. Pederson SL,
    3. Tupper DE,
    4. Hochhalter AK,
    5. Miller WA,
    6. Li Q,
    7. Zaun D,
    8. Collins AJ,
    9. Kane R,
    10. Foley RN
    : Acute variation in cognitive function in hemodialysis patients: A cohort study with repeated measures. Am J Kidney Dis 50: 270–278, 2007pmid:17660028
    OpenUrlCrossRefPubMed
  19. ↵
    1. Buoncristiani U,
    2. Alberti A,
    3. Gubbiotti G,
    4. Mazzotta G,
    5. Gallai V,
    6. Quintaliani G,
    7. Gaburri M
    : Better preservation of cognitive faculty in continuous ambulatory peritoneal dialysis. Perit Dial Int 13[Suppl 2]: S202–S205, 1993pmid:8399566
    OpenUrlAbstract
  20. ↵
    1. Tilki HE,
    2. Akpolat T,
    3. Tunali G,
    4. Kara A,
    5. Onar MK
    : Effects of haemodialysis and continuous ambulatory peritoneal dialysis on P300 cognitive potentials in uraemic patients. Ups J Med Sci 109: 43–48, 2004pmid:15124952
    OpenUrlCrossRefPubMed
  21. ↵
    1. Radić J,
    2. Ljutić D,
    3. Radić M,
    4. Kovačić V,
    5. Dodig-Ćurković K,
    6. Šain M
    : Kidney transplantation improves cognitive and psychomotor functions in adult hemodialysis patients. Am J Nephrol 34: 399–406, 2011pmid:21934300
    OpenUrlCrossRefPubMed
  22. ↵
    1. Hailpern SM,
    2. Melamed ML,
    3. Cohen HW,
    4. Hostetter TH
    : 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 18: 2205–2213, 2007pmid:17554148
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Kurella M,
    2. Chertow GM,
    3. Fried LF,
    4. Cummings SR,
    5. Harris T,
    6. Simonsick E,
    7. Satterfield S,
    8. Ayonayon H,
    9. Yaffe K
    : Chronic kidney disease and cognitive impairment in the elderly: The health, aging, and body composition study. J Am Soc Nephrol 16: 2127–2133, 2005pmid:15888561
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Yaffe K,
    2. Ackerson L,
    3. Kurella Tamura M,
    4. Le Blanc P,
    5. Kusek JW,
    6. Sehgal AR,
    7. Cohen D,
    8. Anderson C,
    9. Appel L,
    10. Desalvo K,
    11. Ojo A,
    12. Seliger S,
    13. Robinson N,
    14. Makos G,
    15. Go AS,
    16. Chronic Renal Insufficiency Cohort Investigators
    : Chronic kidney disease and cognitive function in older adults: Findings from the chronic renal insufficiency cohort cognitive study. J Am Geriatr Soc 58: 338–345, 2010pmid:20374407
    OpenUrlCrossRefPubMed
  25. ↵
    1. Buchman AS,
    2. Tanne D,
    3. Boyle PA,
    4. Shah RC,
    5. Leurgans SE,
    6. Bennett DA
    : Kidney function is associated with the rate of cognitive decline in the elderly. Neurology 73: 920–927, 2009pmid:19657107
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Etgen T,
    2. Sander D,
    3. Chonchol M,
    4. Briesenick C,
    5. Poppert H,
    6. Förstl H,
    7. Bickel H
    : Chronic kidney disease is associated with incident cognitive impairment in the elderly: The INVADE study. Nephrol Dial Transplant 24: 3144–3150, 2009pmid:19461010
    OpenUrlCrossRefPubMed
  27. ↵
    1. Kurella Tamura M,
    2. Wadley V,
    3. Yaffe K,
    4. McClure LA,
    5. Howard G,
    6. Go R,
    7. Allman RM,
    8. Warnock DG,
    9. McClellan W
    : Kidney function and cognitive impairment in US adults: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Am J Kidney Dis 52: 227–234, 2008pmid:18585836
    OpenUrlCrossRefPubMed
  28. ↵
    1. Seliger SL,
    2. Siscovick DS,
    3. Stehman-Breen CO,
    4. Gillen DL,
    5. Fitzpatrick A,
    6. Bleyer A,
    7. Kuller LH
    : Moderate renal impairment and risk of dementia among older adults: The Cardiovascular Health Cognition Study. J Am Soc Nephrol 15: 1904–1911, 2004pmid:15213280
    OpenUrlAbstract/FREE Full Text
  29. ↵
    1. Helmer C,
    2. Stengel B,
    3. Metzger M,
    4. Froissart M,
    5. Massy ZA,
    6. Tzourio C,
    7. Berr C,
    8. Dartigues JF
    : Chronic kidney disease, cognitive decline, and incident dementia: The 3C Study. Neurology 77: 2043–2051, 2011pmid:22116945
    OpenUrlAbstract/FREE Full Text
  30. ↵
    1. Slinin Y,
    2. Paudel ML,
    3. Ishani A,
    4. Taylor BC,
    5. Yaffe K,
    6. Murray AM,
    7. Fink HA,
    8. Orwoll ES,
    9. Cummings SR,
    10. Barrett-Connor E,
    11. Jassal S,
    12. Ensrud KE,
    13. Osteoporotic Fractures in Men Study Group
    : Kidney function and cognitive performance and decline in older men. J Am Geriatr Soc 56: 2082–2088, 2008pmid:18795984
    OpenUrlCrossRefPubMed
  31. ↵
    1. Murray AM
    : Cognitive impairment in the aging dialysis and chronic kidney disease populations: An occult burden. Adv Chronic Kidney Dis 15: 123–132, 2008pmid:18334236
    OpenUrlCrossRefPubMed
  32. ↵
    1. Passer JA
    : Cerebral atrophy in end-stage uremia. Proc Clin Dial Transplant Forum 7: 91–94, 1977pmid:616005
    OpenUrlPubMed
  33. ↵
    1. Kamata T,
    2. Hishida A,
    3. Takita T,
    4. Sawada K,
    5. Ikegaya N,
    6. Maruyama Y,
    7. Miyajima H,
    8. Kaneko E
    : Morphologic abnormalities in the brain of chronically hemodialyzed patients without cerebrovascular disease. Am J Nephrol 20: 27–31, 2000pmid:10644864
    OpenUrlCrossRefPubMed
  34. ↵
    1. Savazzi GM,
    2. Cusmano F,
    3. Musini S
    : Cerebral imaging changes in patients with chronic renal failure treated conservatively or in hemodialysis. Nephron 89: 31–36, 2001pmid:11528229
    OpenUrlCrossRefPubMed
  35. ↵
    1. Cusmano F,
    2. Savazzi GM
    : Cerebral computed tomography in uremic and hemodialyzed patients. J Comput Assist Tomogr 10: 567–570, 1986pmid:3734196
    OpenUrlCrossRefPubMed
  36. ↵
    1. Bugnicourt JM,
    2. Chillon JM,
    3. Massy ZA,
    4. Canaple S,
    5. Lamy C,
    6. Deramond H,
    7. Godefroy O
    : High prevalence of intracranial artery calcification in stroke patients with CKD: A retrospective study. Clin J Am Soc Nephrol 4: 284–290, 2009pmid:19158370
    OpenUrlAbstract/FREE Full Text
  37. ↵
    1. Chillon JM,
    2. Mozar A,
    3. Six I,
    4. Maizel J,
    5. Bugnicourt JM,
    6. Kamel S,
    7. Slama M,
    8. Brazier M,
    9. Massy ZA
    : Pathophysiological mechanisms and consequences of cardiovascular calcifications: Role of uremic toxicity. Ann Pharm Fr 67: 234–240, 2009pmid:19596096
    OpenUrlCrossRefPubMed
  38. ↵
    1. Vermeer SE,
    2. Prins ND,
    3. den Heijer T,
    4. Hofman A,
    5. Koudstaal PJ,
    6. Breteler MM
    : Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 348: 1215–1222, 2003pmid:12660385
    OpenUrlCrossRefPubMed
  39. ↵
    1. Vermeer SE,
    2. Longstreth WT Jr,
    3. Koudstaal PJ
    : Silent brain infarcts: A systematic review. Lancet Neurol 6: 611–619, 2007pmid:17582361
    OpenUrlCrossRefPubMed
  40. ↵
    1. Kobayashi M,
    2. Hirawa N,
    3. Morita S,
    4. Yatsu K,
    5. Kobayashi Y,
    6. Yamamoto Y,
    7. Saka S,
    8. Toya Y,
    9. Yasuda G,
    10. Umemura S
    : Silent brain infarction and rapid decline of kidney function in patients with CKD: A prospective cohort study. Am J Kidney Dis 56: 468–476, 2010pmid:20537454
    OpenUrlCrossRefPubMed
  41. ↵
    1. Kim CD,
    2. Lee HJ,
    3. Kim DJ,
    4. Kim BS,
    5. Shin SK,
    6. Do JY,
    7. Jang MH,
    8. Park SH,
    9. Kim YS,
    10. Kim YL
    : High prevalence of leukoaraiosis in cerebral magnetic resonance images of patients on peritoneal dialysis. Am J Kidney Dis 50: 98–107, 2007pmid:17591529
    OpenUrlCrossRefPubMed
  42. ↵
    1. Schmidt R,
    2. Schmidt H,
    3. Curb JD,
    4. Masaki K,
    5. White LR,
    6. Launer LJ
    : Early inflammation and dementia: A 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol 52: 168–174, 2002pmid:12210786
    OpenUrlCrossRefPubMed
  43. ↵
    1. Pantoni L
    : Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9: 689–701, 2010pmid:20610345
    OpenUrlCrossRefPubMed
  44. ↵
    1. Ikram MA,
    2. Vernooij MW,
    3. Hofman A,
    4. Niessen WJ,
    5. van der Lugt A,
    6. Breteler MM
    : Kidney function is related to cerebral small vessel disease. Stroke 39: 55–61, 2008pmid:18048865
    OpenUrlAbstract/FREE Full Text
    1. Khatri M,
    2. Wright CB,
    3. Nickolas TL,
    4. Yoshita M,
    5. Paik MC,
    6. Kranwinkel G,
    7. Sacco RL,
    8. DeCarli C
    : Chronic kidney disease is associated with white matter hyperintensity volume: The Northern Manhattan Study (NOMAS). Stroke 38: 3121–3126, 2007pmid:17962588
    OpenUrlAbstract/FREE Full Text
  46. ↵
    1. Wada M,
    2. Nagasawa H,
    3. Kurita K,
    4. Koyama S,
    5. Arawaka S,
    6. Kawanami T,
    7. Tajima K,
    8. Daimon M,
    9. Kato T
    : Cerebral small vessel disease and C-reactive protein: Results of a cross-sectional study in community-based Japanese elderly. J Neurol Sci 264: 43–49, 2008pmid:17673235
    OpenUrlCrossRefPubMed
  47. ↵
    1. Martinez-Vea A,
    2. Salvadó E,
    3. Bardají A,
    4. Gutierrez C,
    5. Ramos A,
    6. García C,
    7. Compte T,
    8. Peralta C,
    9. Broch M,
    10. Pastor R,
    11. Angelet P,
    12. Marcas L,
    13. Saurí A,
    14. Oliver JA
    : Silent cerebral white matter lesions and their relationship with vascular risk factors in middle-aged predialysis patients with CKD. Am J Kidney Dis 47: 241–250, 2006pmid:16431253
    OpenUrlCrossRefPubMed
  48. ↵
    1. Debette S,
    2. Beiser A,
    3. DeCarli C,
    4. Au R,
    5. Himali JJ,
    6. Kelly-Hayes M,
    7. Romero JR,
    8. Kase CS,
    9. Wolf PA,
    10. Seshadri S
    : Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: The Framingham Offspring Study. Stroke 41: 600–606, 2010pmid:20167919
    OpenUrlAbstract/FREE Full Text
  49. ↵
    1. Yokoyama S,
    2. Hirano H,
    3. Uomizu K,
    4. Kajiya Y,
    5. Tajitsu K,
    6. Kusumoto K
    : High incidence of microbleeds in hemodialysis patients detected by T2*-weighted gradient-echo magnetic resonance imaging. Neurol Med Chir (Tokyo) 45: 556–560, discussion 560, 2005pmid:16308513
    OpenUrlCrossRefPubMed
  50. ↵
    1. Shima H,
    2. Ishimura E,
    3. Naganuma T,
    4. Yamazaki T,
    5. Kobayashi I,
    6. Shidara K,
    7. Mori K,
    8. Takemoto Y,
    9. Shoji T,
    10. Inaba M,
    11. Okamura M,
    12. Nakatani T,
    13. Nishizawa Y
    : Cerebral microbleeds in predialysis patients with chronic kidney disease. Nephrol Dial Transplant 25: 1554–1559, 2010pmid:20037183
    OpenUrlCrossRefPubMed
  51. ↵
    1. Cho AH,
    2. Lee SB,
    3. Han SJ,
    4. Shon YM,
    5. Yang DW,
    6. Kim BS
    : Impaired kidney function and cerebral microbleeds in patients with acute ischemic stroke. Neurology 73: 1645–1648, 2009pmid:19917986
    OpenUrlAbstract/FREE Full Text
  52. ↵
    1. Ovbiagele B,
    2. Liebeskind DS,
    3. Pineda S,
    4. Saver JL
    : Strong independent correlation of proteinuria with cerebral microbleeds in patients with stroke and transient ischemic attack. Arch Neurol 67: 45–50, 2010pmid:20065128
    OpenUrlCrossRefPubMed
  53. ↵
    1. Watanabe A
    : Cerebral microbleeds and intracerebral hemorrhages in patients on maintenance hemodialysis. J Stroke Cerebrovasc Dis 16: 30–33, 2007pmid:17689389
    OpenUrlCrossRefPubMed
  54. ↵
    1. Lee M,
    2. Saver JL,
    3. Chang KH,
    4. Liao HW,
    5. Chang SC,
    6. Ovbiagele B
    : Low glomerular filtration rate and risk of stroke: meta-analysis. BMJ 341: c4249, 2010pmid:20884696
    OpenUrlAbstract/FREE Full Text
  55. ↵
    1. Mogi M,
    2. Horiuchi M
    : Clinical interaction between brain and kidney in small vessel disease. Cardiol Res Pract 2011: 306189, 2011pmid:21274446
    OpenUrlCrossRefPubMed
  56. ↵
    1. Silvestrini M,
    2. Pasqualetti P,
    3. Baruffaldi R,
    4. Bartolini M,
    5. Handouk Y,
    6. Matteis M,
    7. Moffa F,
    8. Provinciali L,
    9. Vernieri F
    : Cerebrovascular reactivity and cognitive decline in patients with Alzheimer disease. Stroke 37: 1010–1015, 2006pmid:16497984
    OpenUrlAbstract/FREE Full Text
  57. ↵
    1. Stefani A,
    2. Sancesario G,
    3. Pierantozzi M,
    4. Leone G,
    5. Galati S,
    6. Hainsworth AH,
    7. Diomedi M
    : CSF biomarkers, impairment of cerebral hemodynamics and degree of cognitive decline in Alzheimer’s and mixed dementia. J Neurol Sci 283: 109–115, 2009pmid:19278690
    OpenUrlCrossRefPubMed
  58. ↵
    1. Vicenzini E,
    2. Ricciardi MC,
    3. Altieri M,
    4. Puccinelli F,
    5. Bonaffini N,
    6. Di Piero V,
    7. Lenzi GL
    : Cerebrovascular reactivity in degenerative and vascular dementia: A transcranial Doppler study. Eur Neurol 58: 84–89, 2007pmid:17565221
    OpenUrlCrossRefPubMed
  59. ↵
    1. O’Brien JT,
    2. Erkinjuntti T,
    3. Reisberg B,
    4. Roman G,
    5. Sawada T,
    6. Pantoni L,
    7. Bowler JV,
    8. Ballard C,
    9. DeCarli C,
    10. Gorelick PB,
    11. Rockwood K,
    12. Burns A,
    13. Gauthier S,
    14. DeKosky ST
    : Vascular cognitive impairment. Lancet Neurol 2: 89–98, 2003pmid:12849265
    OpenUrlCrossRefPubMed
  60. ↵
    1. Reed BR,
    2. Mungas DM,
    3. Kramer JH,
    4. Ellis W,
    5. Vinters HV,
    6. Zarow C,
    7. Jagust WJ,
    8. Chui HC
    : Profiles of neuropsychological impairment in autopsy-defined Alzheimer’s disease and cerebrovascular disease. Brain 130: 731–739, 2007pmid:17267522
    OpenUrlCrossRefPubMed
  61. ↵
    1. Madero M,
    2. Gul A,
    3. Sarnak MJ
    : Cognitive function in chronic kidney disease. Semin Dial 21: 29–37, 2008pmid:18251955
    OpenUrlCrossRefPubMed
  62. ↵
    1. Romero JR,
    2. Beiser A,
    3. Seshadri S,
    4. Benjamin EJ,
    5. Polak JF,
    6. Vasan RS,
    7. Au R,
    8. DeCarli C,
    9. Wolf PA
    : Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: The Framingham study. Stroke 40: 1590–1596, 2009pmid:19265054
    OpenUrlAbstract/FREE Full Text
  63. ↵
    1. Vidal JS,
    2. Sigurdsson S,
    3. Jonsdottir MK,
    4. Eiriksdottir G,
    5. Thorgeirsson G,
    6. Kjartansson O,
    7. Garcia ME,
    8. van Buchem MA,
    9. Harris TB,
    10. Gudnason V,
    11. Launer LJ
    : Coronary artery calcium, brain function and structure: The AGES-Reykjavik Study. Stroke 41: 891–897, 2010pmid:20360538
    OpenUrlAbstract/FREE Full Text
  64. ↵
    1. Massy ZA
    : Importance of homocysteine, lipoprotein (a) and non-classical cardiovascular risk factors (fibrinogen and advanced glycation end-products) for atherogenesis in uraemic patients. Nephrol Dial Transplant 15[Suppl 5]: 81–91, 2000pmid:11073279
    OpenUrlCrossRefPubMed
  65. ↵
    1. Seshadri S,
    2. Wolf PA,
    3. Beiser AS,
    4. Selhub J,
    5. Au R,
    6. Jacques PF,
    7. Yoshita M,
    8. Rosenberg IH,
    9. D’Agostino RB,
    10. DeCarli C
    : Association of plasma total homocysteine levels with subclinical brain injury: Cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study. Arch Neurol 65: 642–649, 2008pmid:18474741
    OpenUrlCrossRefPubMed
  66. ↵
    1. Fassbender K,
    2. Mielke O,
    3. Bertsch T,
    4. Nafe B,
    5. Fröschen S,
    6. Hennerici M
    : Homocysteine in cerebral macroangiography and microangiopathy. Lancet 353: 1586–1587, 1999pmid:10334261
    OpenUrlCrossRefPubMed
  67. ↵
    1. Hassan A,
    2. Hunt BJ,
    3. O’Sullivan M,
    4. Bell R,
    5. D’Souza R,
    6. Jeffery S,
    7. Bamford JM,
    8. Markus HS
    : Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain 127: 212–219, 2004pmid:14607791
    OpenUrlCrossRefPubMed
  68. ↵
    1. Wright CB,
    2. Paik MC,
    3. Brown TR,
    4. Stabler SP,
    5. Allen RH,
    6. Sacco RL,
    7. DeCarli C
    : Total homocysteine is associated with white matter hyperintensity volume: The Northern Manhattan Study. Stroke 36: 1207–1211, 2005pmid:15879345
    OpenUrlAbstract/FREE Full Text
  69. ↵
    1. Lipton SA,
    2. Kim WK,
    3. Choi YB,
    4. Kumar S,
    5. D’Emilia DM,
    6. Rayudu PV,
    7. Arnelle DR,
    8. Stamler JS
    : Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A 94: 5923–5928, 1997pmid:9159176
    OpenUrlAbstract/FREE Full Text
  70. ↵
    1. Seshadri S
    : Elevated plasma homocysteine levels: risk factor or risk marker for the development of dementia and Alzheimer’s disease? J Alzheimers Dis 9: 393–398, 2006pmid:16917147
    OpenUrlPubMed
  71. ↵
    1. Kwok T,
    2. Lee J,
    3. Law CB,
    4. Pan PC,
    5. Yung CY,
    6. Choi KC,
    7. Lam LC
    : A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin Nutr 30: 297–302, 2011pmid:21216507
    OpenUrlCrossRefPubMed
  72. ↵
    1. Duron E,
    2. Hanon O
    : Vascular risk factors, cognitive decline, and dementia. Vasc Health Risk Manag 4: 363–381, 2008pmid:18561512
    OpenUrlPubMed
  73. ↵
    1. Duron E,
    2. Hanon O
    : Antihypertensive treatments, cognitive decline, and dementia. J Alzheimers Dis 20: 903–914, 2010pmid:20182022
    OpenUrlPubMed
  74. ↵
    1. in’t Veld BA,
    2. Ruitenberg A,
    3. Hofman A,
    4. Stricker BH,
    5. Breteler MM
    : Antihypertensive drugs and incidence of dementia: The Rotterdam Study. Neurobiol Aging 22: 407–412, 2001pmid:11378246
    OpenUrlCrossRefPubMed
  75. ↵
    1. Forette F,
    2. Seux ML,
    3. Staessen JA,
    4. Thijs L,
    5. Babarskiene MR,
    6. Babeanu S,
    7. Bossini A,
    8. Fagard R,
    9. Gil-Extremera B,
    10. Laks T,
    11. Kobalava Z,
    12. Sarti C,
    13. Tuomilehto J,
    14. Vanhanen H,
    15. Webster J,
    16. Yodfat Y,
    17. Birkenhäger WH,
    18. Systolic Hypertension in Europe Investigators
    : The prevention of dementia with antihypertensive treatment: New evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 162: 2046–2052, 2002pmid:12374512
    OpenUrlCrossRefPubMed
  76. ↵
    1. Forette F,
    2. Seux ML,
    3. Staessen JA,
    4. Thijs L,
    5. Birkenhäger WH,
    6. Babarskiene MR,
    7. Babeanu S,
    8. Bossini A,
    9. Gil-Extremera B,
    10. Girerd X,
    11. Laks T,
    12. Lilov E,
    13. Moisseyev V,
    14. Tuomilehto J,
    15. Vanhanen H,
    16. Webster J,
    17. Yodfat Y,
    18. Fagard R
    : Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 352: 1347–1351, 1998pmid:9802273
    OpenUrlCrossRefPubMed
  77. ↵
    1. Fournier A,
    2. Oprisiu-Fournier R,
    3. Serot JM,
    4. Godefroy O,
    5. Achard JM,
    6. Faure S,
    7. Mazouz H,
    8. Temmar M,
    9. Albu A,
    10. Bordet R,
    11. Hanon O,
    12. Gueyffier F,
    13. Wang J,
    14. Black S,
    15. Sato N
    : Prevention of dementia by antihypertensive drugs: How AT1-receptor-blockers and dihydropyridines better prevent dementia in hypertensive patients than thiazides and ACE-inhibitors. Expert Rev Neurother 9: 1413–1431, 2009pmid:19769454
    OpenUrlCrossRefPubMed
  78. ↵
    1. Stinghen AE,
    2. Pecoits-Filho R
    : Vascular damage in kidney disease: Beyond hypertension. Int J Hypertens 2011: 232683, 2011pmid:21876786
    OpenUrlCrossRefPubMed
  79. ↵
    1. Seifter JL,
    2. Samuels MA
    : Uremic encephalopathy and other brain disorders associated with renal failure. Semin Neurol 31: 139–143, 2011pmid:21590619
    OpenUrlCrossRefPubMed
  80. ↵
    1. De Deyn PP,
    2. Vanholder R,
    3. Eloot S,
    4. Glorieux G
    : Guanidino compounds as uremic (neuro)toxins. Semin Dial 22: 340–345, 2009pmid:19708978
    OpenUrlCrossRefPubMed
  81. ↵
    1. D’Hooge R,
    2. Pei YQ,
    3. Marescau B,
    4. De Deyn PP
    : Convulsive action and toxicity of uremic guanidino compounds: Behavioral assessment and relation to brain concentration in adult mice. J Neurol Sci 112: 96–105, 1992pmid:1469446
    OpenUrlCrossRefPubMed
  82. ↵
    1. Perna AF,
    2. Ingrosso D,
    3. Satta E,
    4. Lombardi C,
    5. Galletti P,
    6. D’Aniello A,
    7. De Santo NG
    : Plasma protein aspartyl damage is increased in hemodialysis patients: Studies on causes and consequences. J Am Soc Nephrol 15: 2747–2754, 2004pmid:15466280
    OpenUrlAbstract/FREE Full Text
  83. ↵
    1. Yaffe K,
    2. Lindquist K,
    3. Shlipak MG,
    4. Simonsick E,
    5. Fried L,
    6. Rosano C,
    7. Satterfield S,
    8. Atkinson H,
    9. Windham BG,
    10. Kurella-Tamura M
    : Cystatin C as a marker of cognitive function in elders: Findings from the health ABC study. Ann Neurol 63: 798–802, 2008pmid:18496846
    OpenUrlCrossRefPubMed
    1. Kurella M,
    2. Yaffe K,
    3. Shlipak MG,
    4. Wenger NK,
    5. Chertow GM
    : Chronic kidney disease and cognitive impairment in menopausal women. Am J Kidney Dis 45: 66–76, 2005pmid:15696445
    OpenUrlCrossRefPubMed
    1. Seliger SL,
    2. Longstreth WT Jr,
    3. Katz R,
    4. Manolio T,
    5. Fried LF,
    6. Shlipak M,
    7. Stehman-Breen CO,
    8. Newman A,
    9. Sarnak M,
    10. Gillen DL,
    11. Bleyer A,
    12. Siscovick DS
    : Cystatin C and subclinical brain infarction. J Am Soc Nephrol 16: 3721–3727, 2005pmid:16236809
    OpenUrlAbstract/FREE Full Text
    1. Kobayashi M,
    2. Hirawa N,
    3. Yatsu K,
    4. Kobayashi Y,
    5. Yamamoto Y,
    6. Saka S,
    7. Andoh D,
    8. Toya Y,
    9. Yasuda G,
    10. Umemura S
    : Relationship between silent brain infarction and chronic kidney disease. Nephrol Dial Transplant 24: 201–207, 2009pmid:18697797
    OpenUrlCrossRefPubMed
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Cognitive Disorders and Dementia in CKD: The Neglected Kidney-Brain Axis
Jean-Marc Bugnicourt, Olivier Godefroy, Jean-Marc Chillon, Gabriel Choukroun, Ziad A. Massy
JASN Mar 2013, 24 (3) 353-363; DOI: 10.1681/ASN.2012050536
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