Mechanisms of cognitive dysfunction in CKD
Open accessAbstract
Cognitive impairment is an increasingly recognized major cause of chronic disability and is commonly found in patients with chronic kidney disease (CKD). Knowledge of the relationship between kidney dysfunction and impaired cognition may improve our understanding of other forms of cognitive dysfunction. Patients with CKD are at an increased risk (compared with the general population) of both dementia and its prodrome, mild cognitive impairment (MCI), which are characterized by deficits in executive functions, memory and attention. Brain imaging in patients with CKD has revealed damage to white matter in the prefrontal cortex and, in animal models, in the subcortical monoaminergic and cholinergic systems, accompanied by widespread macrovascular and microvascular damage. Unfortunately, current interventions that target cardiovascular risk factors (such as anti-hypertensive drugs, anti-platelet agents and statins) seem to have little or no effect on CKD-associated MCI, suggesting that the accumulation of uraemic neurotoxins may be more important than disturbed haemodynamic factors or lipid metabolism in MCI pathogenesis. Experimental models show that the brain monoaminergic system is susceptible to uraemic neurotoxins and that this system is responsible for the altered sleep pattern commonly observed in patients with CKD. Neural progenitor cells and the glymphatic system, which are important in Alzheimer disease pathogenesis, may also be involved in CKD-associated MCI. More detailed study of CKD-associated MCI is needed to fully understand its clinical relevance, underlying pathophysiology, possible means of early diagnosis and prevention, and whether there may be novel approaches and potential therapies with wider application to this and other forms of cognitive decline.
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Renal insufficiency leads to increased levels of circulating uraemic neurotoxins such as parathyroid hormone and neuropeptide Y, which adversely affect hippocampal neuronal apoptosis and the permeability of the blood-brain barrier, respectively.
“In addition, renal insufficiency also leads to increased levels of circulating uraemic neurotoxins such as parathyroid hormone and neuropeptide Y, which adversely affect hippocampal neuronal apoptosis and the permeability of the BBB, respectively.257”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [257]
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- Simões E Silva, A. C., Miranda, A. S., Rocha, N. P. & Teixeira, A. L. Neuropsychiatric Disorders in Chronic Kidney Disease. Front. Pharmacol. 10, 932 (2019).
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- Authors
- Viggiano, D., Wagner, C. A., Martino, G., Nedergaard, M., Zoccali, C., Unwin, R., & Capasso, G.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- University of Zurich (CH)
- Vita-Salute San Raffaele University (IT)
- University of Rochester Medicine (US)
- National Research Council (IT)
- AstraZeneca (United Kingdom) (GB)
- Corresponding author
- Capasso, Giovambattista
- ORCID
- Venue
- Nature Reviews Nephrology
- Published
- 2020-03-31
- Volume
- 16
- Issue
- 8
- Pages
- 452-469
- ISSN
- 1745-8323 (ISSN-L)
- 1759-5061
- 1759-507X
- OpenAlex
- W3015186969
- Cited by
- 392
- References
- 253
- Citations by year
- 2026: 60 · 2025: 106 · 2024: 63 · 2023: 56 · 2022: 56 · 2021: 40 · 2020: 10
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Reviews Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Lundbeckfonden (R155-2016–552)
- Novo Nordisk Fonden (NNF13OC0004258)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- chronic kidney disease, cognitive impairment, mild cognitive impairment, dementia, monoaminergic systems, cholinergic system, white matter injury, prefrontal cortex, sleep disorders, glymphatic system, neural progenitor cells, microvascular damage, executive function, attention and memory
- MeSH terms
- Glymphatic System, Animals, Cerebrovascular Circulation, Cerebrovascular Disorders, Hemodynamics, Humans, Risk Factors, Sleep Wake Disorders, Uremia, Renal Replacement Therapy, Genetic Predisposition to Disease, Lipid Metabolism, Renal Insufficiency, Chronic, Leukoencephalopathies, Neural Stem Cells, Cognitive Dysfunction
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