Kidney Disease Linked to Accelerated Cognitive Decline, With Distinct Impacts on Men and Women
A new study reveals a concerning connection between chronic kidney disease (CKD) and a faster rate of cognitive decline, highlighting how damage to the heart and brain are interconnected in this process. Published in the American Journal of Physiology – Heart and Circulatory Physiology on January 1, 2025, the research underscores the urgent need for tailored treatment strategies, as the biological pathways involved differ significantly between men and women.
The global prevalence of CKD is rising rapidly, affecting an estimated 11% to 13% of the population. This escalating health challenge is driven by factors like aging, hypertension, and type 2 diabetes, all of which contribute to nephron loss and kidney injury. Researchers have long suspected a link between kidney dysfunction and cognitive impairment, with previous studies in animal models confirming CKD as an independent risk factor. In advanced stages of CKD (stages 4–5), cognitive impairment is observed in approximately 30% to 60% of patients – double the rate seen in age- and sex-matched individuals with healthy kidneys.
The study points to a complex interplay of factors – including oxidative stress, uremic toxicity, inflammation, and cardiovascular damage – that create a “kidney-heart-brain axis” contributing to cognitive issues and potentially leading to more serious neurological disorders. “These results demonstrate that the biological pathways linking the kidney, heart, and brain are distinct in men and women,” explained Sneha S. Pillai, PhD, a research assistant professor of biomedical sciences at the Joan C. Edwards School of Medicine.
Researchers conducted a cross-sectional study involving both individuals with CKD and a control group from a rural community. Participants underwent assessments of kidney and cardiovascular health, cognitive function using the Mini-Mental State Examination (MMSE), and biomarkers related to fibrosis and neurodegeneration. Analysis included linear regression and structural equation modeling to pinpoint sex-specific associations.
The findings revealed that both men and women with CKD scored lower on the MMSE compared to their healthy counterparts. However, a notable difference emerged: women with CKD consistently demonstrated better cognitive performance than men with the disease. Approximately 20% of women with CKD scored 24 or lower on the MMSE, while nearly half (48%) of the men with CKD fell into that range.
Further analysis of individual MMSE test domains showed declines in Language, Attention and Calculation, Recall, and Copy Design for both men and women with CKD. Importantly, men with CKD exhibited more significant deficits in Recall – a measure of short-term memory – and Language skills compared to women with the condition. Path analysis revealed a direct link between plasma phosphorylated Tau protein (pTau) and the ratio of amyloid β-42 to amyloid β-40 with MMSE scores, but only in women.
“Understanding how cardiovascular stress and neurodegenerative markers interact differently in men and women with CKD could fundamentally change how we approach treatment,” stated Komal Sodhi, MD, an associate professor of surgery at the Joan C. Edwards School of Medicine. “This work underscores the urgency of tailored strategies to prevent progression to more serious neurological disorders.”
The study authors acknowledge limitations, including a relatively small sample size and the cross-sectional design, which prevents establishing cause-and-effect relationships. They also noted inherent differences in cognitive strengths between men and women (such as visuospatial skills in men and verbal fluency in women). Future research, they urge, should address these limitations through larger, longitudinal studies with more diverse populations and more comprehensive clinical data. .
References:
- Pillai SS, Morrell CH, Dos Santos CR, et al. Chronic kidney disease and cardiac remodeling potentiate cognitive impairment progression: disentangling the sex-specific cross talk of kidney-heart-brain axis. Am J Physiol Heart Circ Physiol. 2025;330(1). doi:10.1152/ajpheart.00617.2025
- Marshall University Joan C. Edwards School of Medicine. Study highlights underrecognized link between kidney disease and cognitive decline. News release. December 4, 2025. Accessed December 19, 2025. https://jcesom.marshall.edu/news/musom-news/study-highlights-underrecognized-link-between-kidney-disease-and-cognitive-decline/
