A study shows that people with higher levels of the protein albumin in their urine are at increased risk of developing dementia. The study, led by researchers at Karolinska Institutet, is published in the scientific journal Journal of Internal Medicine.
Although age remains the biggest risk factor for developing dementia, researchers have increasingly shown that diseases in other parts of the body, such as the kidneys, can also affect the brain.
In the new study, the researchers were able to show that people with higher levels of albumin in their urine, an abnormal condition known as albuminuria (see fact box), are at increased risk of developing dementia later in life.
This association was strongest for vascular dementia, the second most common form of dementia after Alzheimer's disease, often caused by stroke, high blood pressure, diabetes, or other vascular diseases, and for mixed dementia, which combines features of vascular dementia and Alzheimer's disease.
The study included 130,000 older adults in Stockholm, all over the age of 65 and free of dementia at the start of the study. During a follow-up period of approximately four years, seven percent of the participants developed dementia.
After taking into account kidney function and other factors, the researchers found that people with moderate levels of the protein albumin in their urine (30–299 mg/g) had a 25 percent higher risk of developing dementia, while those with high levels (≥300 mg/g) had a 37 percent higher risk compared to people with normal levels (<30 mg/g).
Higher levels of this protein indicate kidney damage and, according to this study, may also signal a higher risk of dementia.
“The kidneys and the brain may seem like very different organs, but they share an important characteristic: both depend on a delicate network of small blood vessels. When the blood vessels in the kidneys are damaged, the same process often occurs in the brain,” says last author Hong Xu, assistant professor at the Department of Neurobiology, Care Sciences and Society at Karolinska Institutet.
An important component is the blood-brain barrier, a protective layer that prevents harmful substances in the blood from entering the brain. Just as a damaged kidney filter leaks proteins into the urine, a damaged blood-brain barrier allows toxins and inflammatory molecules to the brain tissue. Over time, this increases the risk of vascular damage, inflammation, and accumulation of harmful proteins linked to dementia.
"These results underscore the importance of routine screening for albuminuria as part of early dementia risk assessment, especially in patients with high blood pressure, diabetes, cardiovascular disease, or kidney disease. Early detection of albuminuria could potentially delay or prevent the onset of dementia," says Hong Xu.
The study was funded by the Center for Innovative Medicine Foundation (CIMED), the Swedish Research Council, the U&L Angeby Foundation, the Petrus and Augusta Hedlund Foundation, and the Åke Wiberg Foundation, among others. The researchers report no conflicts of interest.
What is albuminuria?
Healthy kidneys act as filters. They remove waste products and excess fluid while retaining important proteins, such as albumin, in the blood. When the filtering function of the kidneys deteriorates, often due to high blood pressure, diabetes, family history of kidney disease, or pregnancy complications, albumin begins to leak into the urine. This protein in the urine is a warning sign that reflects endothelial dysfunction and vascular damage, , especially in the kidneys. This condition, called albuminuria, is already used as an early marker for kidney disease and cardiovascular disease.