TLDR: This study provides evidence that high salt intake is causally associated with an increased risk of developing dementia, including Alzheimer’s disease (AD) and undefined dementia.
Highlights:
- Causal Association: High salt intake is significantly associated with an increased risk of any dementia (OR = 1.73) and specifically Alzheimer’s disease (OR = 2.10).
- Cognitive Performance: Higher salt intake is linked to lower cognitive performance (β = -0.133).
- Undefined Dementia: Salt intake increases the risk of undefined dementia (OR = 2.61).
- Alzheimer’s Disease Risk: Elevated salt intake significantly raises the risk of developing Alzheimer’s disease (OR = 1.80).
- Specific Dementia: No significant association was found between high salt intake and other specific types of dementia such as vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB).
Source: Brain & Behavior (2024)
Historical Links: Salt Intake & Dementia
Early Observations
Early epidemiological studies observed higher rates of cognitive decline and dementia in populations with high sodium diets.
These studies suggested that excessive salt intake might be linked to hypertension, a well-known risk factor for vascular dementia.
Hypertension can cause damage to blood vessels in the brain, leading to reduced blood flow and an increased risk of cognitive impairment and dementia.
Animal Studies
Animal research further supported these findings.
Rodent studies demonstrated that a high-salt diet could directly impact brain function.
- Increased Tau Protein Phosphorylation: High salt intake was shown to induce pathological changes such as increased phosphorylation of tau proteins, which are associated with neurofibrillary tangles found in Alzheimer’s disease.
- Amyloid Beta Accumulation: Salt-rich diets were linked to the accumulation of amyloid beta plaques, another hallmark of Alzheimer’s disease.
Human Studies
Observational studies in humans have explored the link between salt intake and cognitive health. Key observations included:
- Hypertension as a Mediator: Many studies pointed to hypertension as a mediator in the relationship between salt intake and dementia. High blood pressure can damage small blood vessels in the brain, leading to microbleeds and white matter lesions, which are associated with cognitive decline.
- Direct Neurological Impact: Some studies suggested that high salt intake might have a direct neurological impact independent of its effects on blood pressure. This includes potential changes in brain structure and function due to high sodium levels.
Major Findings: Salt Intake & Dementia in Europeans (2024)
The study employed a Mendelian randomization design to investigate the causal impact of salt intake on the risk of dementia.
It utilized genetic data to assess the relationship between high salt consumption and various forms of dementia, including Alzheimer’s disease (AD).
1. Causal Relationship with Dementia
Any Dementia: High salt intake was found to be causally associated with an increased risk of developing any type of dementia. The odds ratio (OR) was 1.73, indicating a 73% higher risk compared to those with lower salt intake.
Alzheimer’s Disease: Specifically, the study found a significant association between high salt intake and the risk of developing Alzheimer’s disease (OR = 2.10), suggesting that individuals with high salt consumption are more than twice as likely to develop AD.
2. Impact on Cognitive Performance
Higher salt intake was linked to lower cognitive performance.
The study reported a negative association (β = -0.133), meaning that increased salt consumption was correlated with a decrease in cognitive abilities.
3. Risk of Undefined Dementia
The study also found a significant association between high salt intake and an increased risk of undefined dementia (OR = 2.61).
Undefined dementia refers to cases where the specific type of dementia could not be determined.
4. Additional Findings
Increased Risk of Alzheimer’s Disease (AD): Beyond general dementia, high salt intake was significantly associated with an increased risk of Alzheimer’s disease (OR = 1.80).
Consistency Across Methods: The study employed multiple analytical methods (MR-Egger, weighted median, MR-PRESSO) to ensure robustness. All methods consistently showed a significant association between high salt intake and the risk of dementia and AD.
Sensitivity Analyses
The study conducted several sensitivity analyses to validate its findings:
- Cochran’s Q Test: Used to evaluate potential heterogeneity.
- MR-Egger Intercept Test: Assessed for horizontal pleiotropy, which occurs when genetic variants influence dementia through pathways other than salt intake.
- MR-PRESSO: Identified and corrected for outliers that could skew results.
- Leave-One-Out Analysis: Checked the influence of individual genetic variants by re-running the analysis after removing each variant one at a time.
These analyses confirmed the stability and credibility of the findings, indicating that the results were not driven by confounding factors or biases.
How Salt Intake Could Increase Risk of Alzheimer’s Disease & Dementia (Possible Mechanisms)
The study suggests that high salt intake is causally associated with an increased risk of Alzheimer’s disease (AD) and dementia.
Hypertension & Vascular Damage
Hypertension: High salt intake can lead to elevated blood pressure, a known risk factor for vascular damage in the brain.
Vascular Damage: High blood pressure can damage small blood vessels in the brain, leading to reduced blood flow, microbleeds, and white matter lesions. These changes can contribute to cognitive impairment and increase the risk of both vascular dementia and Alzheimer’s disease.
Inflammation
Chronic Inflammation: High salt levels can trigger chronic inflammatory responses in the brain.
Neuroinflammation: This inflammation can promote neurodegeneration, damaging neurons and supporting cells, thus contributing to the development and progression of Alzheimer’s disease and other forms of dementia.
Blood-Brain Barrier Disruption
Integrity Compromise: Excessive salt intake may affect the integrity of the blood-brain barrier (BBB), a protective layer that controls the passage of substances from the blood into the brain.
Increased Permeability: A compromised BBB allows harmful substances to enter the brain more easily, potentially leading to neuronal damage and cognitive decline.
Hormonal Changes
Angiotensin II: High salt intake can influence the levels of hormones such as angiotensin II, which is involved in regulating blood pressure and fluid balance.
Cognitive Effects: Elevated levels of angiotensin II have been linked to cognitive impairment and neuroinflammation, further increasing the risk of dementia and Alzheimer’s disease.
Direct Neurological Impact
Tau Protein Phosphorylation: High salt intake may directly impact brain proteins such as tau. Increased phosphorylation of tau proteins is associated with neurofibrillary tangles, a hallmark of Alzheimer’s disease.
Amyloid Beta Accumulation: Salt-rich diets may contribute to the accumulation of amyloid beta plaques, another hallmark of Alzheimer’s disease, which disrupts neuronal communication and triggers neuroinflammation.
Dementia Risk & Dietary Salt Intake: Mendelian Randomization Study (2024)
Sample
Exposure Data: Genetic variants associated with salt intake were obtained from the UK Biobank, comprising 462,630 individuals of European ancestry.
Outcome Data: Data for various forms of dementia and cognitive performance were sourced from the IEU OpenGWAS database, including:
- Any Dementia: 216,771 individuals (7,284 cases and 209,487 controls)
- Cognitive Performance: 257,841 individuals
- Alzheimer’s Disease (AD): 211,678 individuals (2,191 cases and 209,487 controls)
- Other Dementias: Various sample sizes for frontotemporal dementia, dementia with Lewy bodies, vascular dementia, and Parkinson’s disease.
Methods
Data Collection: Genetic data from genome-wide association studies (GWAS) were utilized. Participants’ frequency of adding salt to foods was assessed using a touchscreen questionnaire.
Mendelian Randomization Analysis
- Primary Method: Inverse-variance weighted (IVW) model.
- Supplementary Methods: MR-Egger, weighted median, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO).
- 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 to ensure the robustness of the findings.
Limitations
- Self-Reported Data: Reliance on self-reported salt intake from a dietary questionnaire introduces potential recall bias and measurement error.
- Non-Direct Measure of Salt Intake: The study assessed salt added to food rather than total salt consumption, which could lead to an underestimation of actual intake.
- Confounding Factors: While efforts were made to exclude SNPs associated with confounders, unmeasured confounding factors might still influence the results.
- Generalizability: The study sample consisted of individuals of European descent, limiting the applicability of the findings to other populations.
- Complex Relationships: The assumed linear relationship between salt intake and dementia risk may oversimplify the actual complex interactions involved.
- Sample Size for Specific Dementias: Some specific types of dementia had relatively small sample sizes, potentially leading to false negative conclusions.
Correlation or Causation? High Dietary Salt Intake & Dementia
Evidence for Causation
Mendelian Randomization (MR): This study uses MR, which leverages genetic variants as instrumental variables to infer causality. This method helps to minimize confounding factors that typically affect observational studies.
Consistent Findings: The study employed multiple MR methods (IVW, MR-Egger, MR-PRESSO) that consistently demonstrated a causal link between high salt intake and increased dementia risk.
Limitations in Proving Causation
Residual Confounding: Although MR helps reduce confounding, it cannot eliminate all potential confounders, especially those not captured by genetic variants.
Population Specificity: The genetic variants and dietary patterns may vary across different populations, which might influence the generalizability of the causal inference.
Conclusion: Salt Intake & Dementia Risk
This study provides robust evidence suggesting a causal relationship between high salt intake and an increased risk of dementia, including Alzheimer’s disease.
By leveraging Mendelian randomization, the researchers were able to address many confounding factors that often complicate observational studies, strengthening the argument for causality.
The findings underscore the importance of dietary interventions in public health strategies aimed at preventing cognitive decline.
Reducing salt consumption could be a simple yet effective measure to lower the incidence of dementia, benefiting individual health outcomes and easing the societal burden of neurodegenerative diseases.
Future research and clinical trials are needed to further validate these findings and to develop targeted prevention strategies.
References
- Study: Association between adding salt in food and dementia in European descent: A mendelian randomization study (2024)
- Authors: Ren Zhou et al.
