New research – published in Neurology, the medical journal of the American Academy of Neurology – suggests that people who have protein in their urine might have higher odds of developing problems with memory and thinking down the line, and they may even develop dementia.

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Protein in urine may be associated with an increased risk of cognitive impairment or dementia.

Researchers trawled through all available publications focused on kidney problems and the development of cognitive impairment or dementia, in order to summarize the best available evidence and connect the dots between the two conditions.

Protein in urine is a sign of kidney problems, which have been deemed a possible risk factor for cognitive impairment and dementia in several studies.

The brain and kidneys are both end organs and share similar structural and mechanical features, which makes them susceptible to vascular damage. Several pathways might link chronic kidney disease (CKD) and cognitive impairment, including the shared vascular factors.

“CKD and dementia share many risk factors, such as high blood pressure, diabetes and high cholesterol, and both show similar effects on the brain, so they may have shared vascular factors or there may even be a direct effect on the brain from kidney problems,” says Kay Deckers, of Maastricht University in the Netherlands, author of the systematic review and meta-analysis.

Around 10 percent of the global population is affected by CKD, and the condition is more likely to occur in older people. The study notes that: “Both CKD and dementia are important public health problems with associated poor health outcomes and rising healthcare costs for our society.”

According to the World Health Organization (WHO), there are currently 47.5 million people worldwide who have dementia, and that number continues to rise, with 7.7 million new cases every year. Identifying the factors that may cause dementia is important given the lack of effective treatments.

The authors of the study say that the exact mechanisms relating kidney impairment to dementia are not entirely understood. However, traditional risk factors and other factors that they have in common may play a part.

The authors write: “Traditional risk factors include cardiovascular disease (e.g., myocardial infarction, atrial fibrillation), stroke, type 2 diabetes mellitus, isolated systolic hypertension, age, smoking, and hypercholesterolemia.”

“Other factors include anemia, albumin, and hyperhomocysteinemia, whereas inflammation, oxidative stress, cerebral small vessel disease, silent brain infarcts, microbleeds, and white matter lesions are possible underlying mechanisms leading to cognitive impairment or dementia.”

Out of 8,494 studies on the conditions, 22 of these met the criteria to be included in the systematic review. Five of the studies – that included a total of 27,805 people – were evaluated in the meta-analysis of the protein that sometimes emerges in urine, called albuminuria or proteinuria.

The analysis found that, compared with individuals without the protein in their urine, people with the urine protein were 35 percent more likely to develop cognitive impairment or dementia.

Deckers and team say that their large population-based study adds to the growing evidence that kidney dysfunction is an independent risk factor for cognitive impairment or dementia.

However, limitations of the study include the fact that most of the studies used different methods for estimating renal function and this was only tested once, usually at the start of the study.

“Protein in the urine was associated with a modestly increased risk of cognitive impairment or dementia. More research is needed to determine whether the kidney problems are a cause of the cognitive problems or if they are both caused by the same mechanisms.”

Kay Deckers

In addition to examining the association of albuminuria, Deckers and colleagues also observed other markers of kidney function. The first marker analyzed was estimated glomerular filtration rate. The results from this marker were mixed and showed no significant relationship with cognitive impairment or dementia.

Analysis of the other three other markers of kidney function – cystatin C, serum creatinine, and creatinine clearance – could not be completed due to too many variations in the approach of the studies, which made them incomparable.

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