Association between adding salt in food and dementia in European descent: A mendelian randomization study

Abstract Background High salt intake has been proposed as a risk factor for dementia. However, causal relationship between salt intake and dementia remains uncertain. Purpose The aim of this study was to employ a mendelian randomization (MR) design to investigate the causal impact of salt intake on the risk of dementia. Methods Genome‐wide association study (GWAS) data of exposures and outcomes (any dementia, cognitive performance, different types of dementia, Alzheimer's disease [AD], and Parkinson's disease) were obtained from the IEU database. MR estimates were generated though inverse‐variance weighted model. MR‐Egger, weighted median, and MR‐Pleiotropy Residual Sum and Outlier (MR‐PRESSO) method also used in our study. Sensitivity analyses included Cochran's Q test, MR‐Egger intercept, MR‐PRESSO global test and outlier test, leave‐one‐out analysis, and funnel plot assessment. Results Our MR analysis provided evidence of a causal association between high salt added to food and dementia (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.21–2.49, and p = .003), dementia in AD (OR = 2.10, 95% CI: 1.15–3.83, and p = .015), and undefined dementia (OR = 2.61, 95% CI: 1.26–5.39, and p = .009). Higher salt added was also associated with increased risk of AD (OR = 1.80, 95% CI: 1.12–2.87, and p = .014) and lower cognitive performance ( β = −.133, 95% CI: −.229 to −.038, and p = .006). Conclusion This study provides evidence suggesting that high salt intake is causally associated with an increased risk of developing dementia, including AD and undefined dementia, highlighting the potential importance of reducing salt consumption as a preventive measure.