Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease
Open accessAbstract
INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. METHODS: We conducted time‐to‐event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow‐up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. RESULTS: Compared to non‐carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. DISCUSSION: CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. Highlights: Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.
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Apparent protective associations with AD may in part reflect competing risks, recruiting bias, or survivor bias in populations with elevated vascular morbidity.
“Apparent protective associations with AD may, in part, reflect competing risks, recruiting bias, or survivor bias in populations with elevated vascular morbidity [18,19].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [19]
The Discussion reports protective associations between CHIP and cognitive impairment in patients with chronic kidney disease and cautions that the observational findings could reflect residual confounding. It speculates about reduced AD risk but does not identify competing risks, recruitment bias, or survivor bias as explanations; AD itself was not the study’s measured outcome. The indexed copy provides section labels but no page numbers. (LLM, conf=0.81)
Experimental — accuracy not yet measuredGene-specific effects, clonal burden, host genetic background, and neurovascular integrity all shape whether CHIP-derived immune cells exert protective or pathogenic influences in the aging brain.
“Gene-specific effects, clonal burden, host genetic background, and neurovascular integrity all shape whether CHIP-derived immune cells exert protective or pathogenic influences in the aging brain [10,11,13,19,33,34].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [19]
The Results section reports differences in cognitive-impairment associations by clone size and some differences by driver gene. Its APOE analysis found only a marginally significant interaction and calls for caution. The paper does not establish that these factors—or neurovascular integrity—determine whether CHIP-derived immune cells are protective or pathogenic; the Discussion says the study cannot determine causality and that the cellular mechanisms remain unknown. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDNMT3A-mutant CHIP has shown protective associations with cognitive outcomes in some population-based and clinical cohorts as well as specific subgroups, particularly for larger clones and in select disease contexts.
“DNMT3A-mutant CHIP has shown protective associations with cognitive outcomes in some population-based and clinical cohorts as well as specific subgroups in these studies, particularly for larger clones and in select disease contexts [10,11,19,33].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [19]
The Results (Table 3; page not provided) associate DNMT3A CHIP with lower risk of impairment on the Trails A test in patients with chronic kidney disease. But the claim’s emphasis on larger clones is contrary to this paper’s findings: the Results and Discussion report a protective association for small clones and no association for large clones. This paper does not itself establish the claim across population-based cohorts. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn the Chronic Renal Insufficiency Cohort, CHIP carriers exhibited a significantly lower risk of impairment in attention and executive function over approximately six years, suggesting domain-specific cognitive protection in chronic kidney disease.
“in the Chronic Renal Insufficiency Cohort, CHIP carriers exhibited a significantly lower risk of impairment when assessed for attention and executive function over a mean follow-up of approximately six years, suggesting domain-specific cognitive protection in patients with chronic kidney disease [19].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [19]
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Cited by
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Kopp, K., Silva, P., Damm, F., & Cosma, N. C. (2026) · Biomedicines · doi:10.3390/biomedicines14051012
- Authors
- Xiao, C., Tamura, M. K., Pan, Y., Rao, V., Missikpode, C., Vlasschaert, C., Nakao, T., Sun, X., Li, C., Huang, Z., Anderson, A., Uddin, M. M., Kim, D., Taliercio, J., Deo, R., Bhat, Z., Xie, D., Rao, P., Chen, J., Lash, J. P., He, J., Natarajan, P., Hixson, J. E., Yaffe, K., Kelly, T. N., & CRIC Study Investigators
- Affiliations
- University of Illinois Chicago (US)
- Stanford Medicine (US)
- Queen's University (CA)
- Broad Institute (US)
- Tulane University (US)
- University of Alabama at Birmingham (US)
- The University of Texas Health Science Center at Houston (US)
- Cleveland Clinic (US)
- University of Pennsylvania (US)
- University of Michigan (US)
- University of California, San Francisco (US)
- Corresponding author
- Kelly, Tanika N.
- ORCID
- Xiao, Cissy
- Tamura, Manjula Kurella
- Pan, Yang
- Missikpode, Celestin
- Vlasschaert, Caitlyn
- Nakao, Tetsushi
- Sun, Xiao
- Li, Changwei
- Huang, Zhijie
- Anderson, Amanda
- Uddin, Md Mesbah
- Taliercio, Jonathan
- Deo, Rajat
- Bhat, Zeenat
- Xie, Dawei
- Rao, Panduranga
- Chen, Jing
- Lash, James P.
- Natarajan, Pradeep
- Hixson, James E.
- Yaffe, Kristine
- Kelly, Tanika N.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2024-08-08
- Volume
- 20
- Issue
- 10
- Pages
- 6960-6971
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC11485087
- OpenAlex
- W4401422101
- Cited by
- 14
- References
- 5
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 2
- FWCI
- 4.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902, U24DK060990)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- clonal hematopoiesis of indeterminate potential, chronic kidney disease
- MeSH terms
- Clonal Hematopoiesis, Aged, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Cohort Studies, Renal Insufficiency, Chronic, Executive Function, Cognitive Dysfunction
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