Chronic Kidney Disease and Dementia Connection: Understanding The Research

Previous research surrounding kidney disease and dementia demonstrated mixed and often conflicting results regarding the relationship between kidney function and the rate of dementia diagnosis. However, more recently, a study designed to evaluate the entire spectrum of kidney function and larger sample sizes indicated a strong relationship.

Below, we take a deep dive into this study, discussing how it compares to previous research surrounding kidney disease and dementia risk and how to address the limitations of current research. 

Kidney Disease and Dementia Risk

According to a five-year study of a health care use cohort published in Neurology in May of 2021, both lower kidney function and steeper kidney function decline are associated with the development of dementia in older adults (≥65 years of age).

Study Design, Outcome Measures, and Results

Because community-based reports surrounding the link between the estimated glomerular filtration rate (eGFR) and dementia risk have shown conflicting results, this study aimed to investigate on a large scale the connections between kidney function, kidney function decline, and dementia incidence. 

eGFR is commonly used in clinical practice to assess kidney function, as this calculation can indicate how well the kidneys are filtering out specific agents produced by the body, such as creatinine and cystatin C.

The study utilized data from the Stockholm Creatinine Measurements (SCREAM) project, which included data from all residents receiving serum creatinine tests between the years 2006 and 2011. This enabled the researchers to analyze more than 90% of the total census population of individuals aged 65 and over (329,822 individuals). Exclusion criteria included any recorded history of dementia, missing information regarding age or sex, and undergoing kidney replacement therapy at cohort entry. 

Study Outcome Measures:

• Primary Outcome: The first recorded diagnosis of all-cause dementia or the initiation of dementia treatment drugs
• Secondary Outcome: The first recorded diagnosis of Alzheimer’s disease-related dementia and vascular dementia

The primary findings of this study were as follows:

• Over a median follow-up of five years, 18,983 cases of dementia were detected.
• Dementia incidence rates were significantly higher with lower eGFR: From 6.56/1,000 person-years in those with eGFR of 90 to 104 mL/min to 30.28/1,000 person-years in those with eGFR <30 mL/min.
• After multivariable adjustment, lower eGFR was associated with a higher dementia risk ((hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.54–1.91 in eGFR 30–59 mL/min; HR 2.62, 95% CI 1.91–3.58 in eGFR <30 mL/min) compared with eGFR of 90 to 104 mL/min).
• A steeper decline in eGFR (decline >2 mL/min/1.73 m³/y) within one year was associated with a higher dementia risk.
• Risk magnitudes were stronger for vascular dementia than for Alzheimer’s disease-related dementia.
• As many as 10% (95% CI 6%–14%) of dementia cases could be attributed to eGFR <60 mL/min/1.73 m³. 

A Comparison With Previous Research Surrounding Kidney Disease and Dementia Risk

Previous studies investigating kidney disease and dementia risk have had mixed findings, with some aligning with the results in the above study and others demonstrating conflicting findings.

For example, a Japanese study published in 2018 that analyzed 1,562 participants ≥60 years of age also observed a higher dementia risk in individuals with eGFR <60 mL/min. On the other hand, studies such as this French population-based Three-City study did not show increased dementia risks for individuals with eGFR <60 mL/min. However, these studies did find that the stratum of eGFR of 45 to 60 mL/min was associated with an increased incidence of vascular dementia.

The discrepancy between the findings may very well be due to the differing study designs and outcome measures. While some study designs involved screening, others involved health care extraction. Similarly, while some study outcome measures involved neuropsychological performance, others related to dementia diagnosis and/or drug dispensations. 

For example, utilizing outcome measures such as scores from traditional neuropsychological assessments (e.g. the Mini-Mental State Exam) may not produce results granular enough to truly understand neurocognitive function and dementia risk. These assessments frequently produce noisy, highly variable results that lack the specificity and granularity to confidently draw conclusions on true neurocognitive function, let alone place them on a disease continuum.

Future studies surrounding kidney disease and dementia risk will likely require more robust outcome measures, assessing a breadth of neurocognitive domains at a highly detailed level. Future studies may also include higher frequency neurocognitive testing to better understand changes in neurocognitive function over time to enable researchers to create more robust associations between kidney function and dementia risk.