Sodium-to-Potassium Ratio and Alzheimer's Disease: A Mendelian Randomization Study
Haruka Yoshida1,2, Takuro Inoue2, Shigenori Suzuki2
1Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka, Kanagawa 238-8522, Japan.
Current Alzheimer Research
|May 5, 2026
Summary
This Mendelian Randomization study found no clear causal link between the urinary sodium-to-potassium ratio and Alzheimer's Disease (AD) risk. Further research is needed to explore potential associations with cognitive decline.
Area of Science:
- Neuroscience
- Genetics
- Public Health
Background:
- Higher urinary sodium-to-potassium (Na/K) ratio linked to hypertension and cardiovascular disease, risk factors for Alzheimer's Disease (AD).
- Mendelian Randomization (MR) used to investigate causal relationships, mitigating confounding and reverse causation.
Purpose of the Study:
- To determine if urinary Na/K ratio causally influences the risk of developing Alzheimer's Disease.
- To leverage genetic variants as instrumental variables for robust causal inference.
Main Methods:
- Two-sample MR study design.
- Utilized 31 single-nucleotide polymorphisms for urinary Na/K ratio.
- Analyzed Genome-Wide Association Study (GWAS) data for AD (n=85,934) and late-onset AD (n=21,982).
Main Results:
- Primary analysis: No statistically significant association between genetically predicted urinary Na/K ratio and AD risk (OR=1.02, 95% CI: 0.77-1.36).
- Sensitivity analysis (clinically diagnosed AD): Higher point estimate (OR=1.49, 95% CI: 0.99-2.24) but still not statistically significant.
- Findings suggest potential, though not statistically confirmed, links to cognitive performance.
Conclusions:
- No clear evidence supports a causal association between urinary Na/K ratio and AD risk.
- Sensitivity analysis indicates a possible association warranting further investigation with larger, clinically confirmed AD datasets.
- Results limited to European ancestry populations; generalizability requires caution.
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