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Mechanisms of cognitive dysfunction in CKD
Viggiano D, Wagner CA, Martino G, Nedergaard M, Zoccali C, Unwin R, Capasso G.. Nature reviews. Nephrology, 2020-03-31
Topic: Risk, prevention and care in population studies
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.
Key findings
- 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.
Why it matters
This review states that people with chronic kidney disease are at increased risk of dementia and mild cognitive impairment, with brain imaging showing white matter damage and vascular injury. It notes that interventions targeting cardiovascular risk factors appear to have little or no effect on CKD-associated cognitive impairment, suggesting uraemic neurotoxins may be more important.
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Study details
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Nephrology) |
| Journal's citation record | 2 / 4 | Nature Reviews Nephrology: journal h-index 224 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 393 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 49.1 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 9.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 4 / 4 | Cited 228 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Giovambattista Capasso: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32235904) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
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Read the original
- DOI: 10.1038/s41581-020-0266-9
- PubMed: 32235904
- Original source →
- Free full text: Nature Reviews Nephrology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Viggiano, D., Wagner, C. A., Martino, G., Nedergaard, M., Zoccali, C., Unwin, R., et al. (2020). Mechanisms of cognitive dysfunction in CKD. Nature reviews. Nephrology. https://doi.org/10.1038/s41581-020-0266-9
Vancouver
Viggiano D, Wagner CA, Martino G, Nedergaard M, Zoccali C, Unwin R, et al. Mechanisms of cognitive dysfunction in CKD. Nature reviews. Nephrology. 2020. doi:10.1038/s41581-020-0266-9. PMID: 32235904.
BibTeX
@article{viggiano2020-32235904,
author = {Viggiano, D. and Wagner, C. A. and Martino, G. and Nedergaard, M. and Zoccali, C. and Unwin, R. and Capasso, G.},
title = {{Mechanisms of cognitive dysfunction in CKD}},
journal = {Nature reviews. Nephrology},
year = {2020},
doi = {10.1038/s41581-020-0266-9},
pmid = {32235904},
url = {https://doi.org/10.1038/s41581-020-0266-9}
}
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