Albuminuria is associated with increased risk of dementia, independent of eGFR: The SCREAM project, 2025, Luo et al.

[Chandelier]

https://onlinelibrary.wiley.com/doi/10.1111/joim.70022

Spoiler: Authors

Li Luo, Ron T. Gansevoort, Lyanne M. Kieneker, Yuanhang Yang, Alessandro Bosi, Rudolf A. de Boer, Casper F. M. Franssen, Maria Eriksdotter, Juan-Jesus Carrero, Hong Xu

Abstract​

Background​

The association between albuminuria and dementia has been insufficiently studied, possibly due to not considering dementia subtypes, the interplay with estimated glomerular filtration rate (eGFR), and the use of varying albuminuria measurement techniques.

Objectives​

This study aimed to investigate the eGFR-independent risk of all-cause and type-specific dementia associated with albuminuria, measured by the urine albumin-creatinine ratio (ACR) and dipstick.

Methods​

The main analysis included 132,869 subjects aged ≥65 years without a history of dementia and with at least one ACR test from the Stockholm Creatinine Measurements (SCREAM) project between 2006 and 2019. The primary and secondary outcomes were the incidence of all-cause dementia and type-specific dementia, respectively. Cox regression models were used to calculate hazard ratios (HRs, 95% CIs).

Results​

During a median follow-up of 3.9 (interquartile ranges, 1.8–7.1) years, 9435 (7%) subjects developed incident dementia. After multivariable adjustments, including eGFR, an ACR level of 30–299 and ≥300 mg/g was associated with a 25% (HR, 1.25; 95% CI, 1.19–1.31) and a 37% (HR, 1.37; 95% CI, 1.23–1.51) higher risk of developing all-cause dementia, respectively, compared to an ACR level of <30 mg/g. Higher ACR levels were also associated with an increased risk of mixed, vascular, and unspecified dementia, but not with Alzheimer's disease. These findings were robust in subjects with at least one dipstick proteinuria test.

Conclusion​

Increased albuminuria is associated with a higher risk of all-cause dementia, particularly mixed, vascular, and unspecified dementia, independent of baseline eGFR and generalizable across different clinical pathways of albuminuria testing.

Graphical Abstract​

 

[Chandelier]

Could your urine predict your dementia risk?

Leaky kidney filters linked to higher dementia risk.

theconversation.com

AI Summary:

Urine as an Early Warning Sign for Dementia

New Research Links Protein in Urine to Dementia Risk

A recent study involving 130,000 participants has found that elevated protein levels in urine—specifically a condition called albuminuria—can significantly increase the risk of developing dementia, even decades before symptoms appear. This connection is especially strong for vascular dementia and mixed dementia, types that are linked to blood vessel damage.

The Kidney-Brain Connection

The study reveals that this increased dementia risk exists regardless of overall kidney function. The kidneys and brain share delicate blood vessel networks, and damage to these vessels—often caused by high blood pressure or diabetes—can lead to both protein leakage into urine and reduced blood flow to the brain. This suggests that the same vascular issues affecting the kidneys could also compromise the brain’s blood-brain barrier, allowing harmful substances to enter and potentially contribute to cognitive decline.

Potential for Prevention Through Existing Treatments

This discovery could open new doors for dementia prevention. Medications such as ACE inhibitors and ARBs, typically used to manage blood pressure and kidney health, may also benefit brain health. Newer drugs like semaglutide (Ozempic) and dapagliflozin, initially developed for diabetes, have also been shown to reduce protein in urine and may hold promise in reducing dementia risk, although more long-term studies are needed.

When to Take Action

Since vascular damage develops gradually, early intervention is key. People over 50—especially those with diabetes, high blood pressure, obesity, or a family history of these conditions—may benefit from regular urine protein testing. Currently, such tests are usually limited to high-risk patients, but broader screening could be considered in the future.

Lifestyle Choices Matter

The encouraging news is that the same lifestyle choices that protect kidney function also support brain health. Quitting smoking, managing blood pressure and blood sugar, eating a balanced diet, and exercising regularly can help reduce the risk of both kidney disease and dementia.

A Simple Test with Big Potential

If validated by future research, a simple and affordable urine dipstick test could become a routine tool for assessing dementia risk. Though there is still no cure for dementia, early detection and preventive strategies offer the best path forward. This study highlights how small, everyday health indicators—like protein in urine—might provide vital clues about future brain health.

 

[Jonathan Edwards]

Not very surprising since albuminuria is very often a sign of generalised vascular leakage. Protein leaking into your brain would very likely increase the chances of it rotting.

 

[Utsikt]

Not very surprising since albuminuria is very often a sign of generalised vascular leakage. Protein leaking into your brain would very likely increase the chances of it rotting.

Do we know what usually causes vascular leaking? And can something be done to reduce vascular leaking?

 

[Jonathan Edwards]

Do we know what usually causes vascular leaking? And can something be done to reduce vascular leaking?

Usually some abnormal protein in the circulation gets into the endothelial filter and makes it leaky. Examples are immune complexes, lupus and after streptococcal infection and amyloid proteins in systemic amyloidosis. Mercury probably binds to basement membrane proteins and has the same effect. In diabetes I am not sure but it may be more to do with damaged endothelial cells.