Does Poor Kidney Function Increase Dementia Risk?

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While kidney disease affects Alzheimer’s biomarkers, it mainly speeds up the expression of underlying brain changes rather than causing dementia, according to research published in Neurology.

Results of previous studies suggest that when the kidneys aren’t working well, certain proteins linked to Alzheimer’s disease can build up in the blood. This may happen because the kidneys can’t clear these proteins effectively, or possibly because kidney problems may directly affect the brain, though experts are still debating this. Studies also disagree on whether poor kidney function actually increases the risk of dementia, with some showing a higher risk and others finding no clear connection.

“There is a need to disentangle the role of kidney function in brain aging and specifically in the development of dementia in real-world settings,” wrote a team of investigators led by Francesca Gasparini, M.D., of the Karolinska Institutet in Stockholm, Sweden.

Investigators analyzed how kidney health may affect blood tests that signal changes in the brain related to Alzheimer’s disease using a group of 2,279 older adults enrolled in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) study. Eligible participants did not have dementia at baseline, which was determined by medical exams and cognitive skills tests. The group had an average age of 72 years, and investigators measured their kidney function using a standard blood test called estimated glomerular filtration rate.

Investigators also measured several Alzheimer’s-related proteins found in the blood, including amyloid, tau, neurofilament light chain (NfL) and glial fibrillary acidic protein — markers that can indicate damage to brain cells or changes linked to neurodegenerative diseases.

People were placed in either the “healthy kidney” group (1,722 people) or the “poor kidney function” group (557 people).

The study found that people with poorer kidney function tended to have higher levels of most Alzheimer’s-related blood biomarkers, except for amyloid. This means that when the kidneys are not filtering well, these proteins may build up in the bloodstream. However, this did not mean that people with impaired kidney function were more likely to develop dementia.

Over more than eight years of follow-up, 221 people in the healthy kidney group and 141 people in the poor kidney function group developed dementia — meaning the rates of new dementia diagnoses were similar between people with reduced kidney function and those with normal kidney function.

One important finding was that among people with reduced kidney function, high levels of NfL — a marker of nerve cell damage — were more strongly linked to developing dementia compared with those with healthy kidneys. This suggests that kidney disease may not cause dementia directly but could make existing brain changes show up sooner or more clearly.

The team also mentioned some limitations to consider. The Alzheimer’s-related blood tests were only taken once, so they couldn’t track how kidney changes over time might influence these markers. The method used to estimate kidney function may not be accurate for people with low muscle mass, and the study had relatively few dementia cases and few participants with severe kidney problems, which makes the results less certain. Also, because most participants were highly educated, White and from one urban area in Sweden, the findings may not apply to more diverse communities.

“While we did not find that having reduced kidney function increased the risk of developing dementia, we did find that impaired kidney function may accelerate the onset of dementia in people who have higher levels of biomarkers,” said Gasparini. “This highlights the need for doctors to consider kidney function when interpreting results of Alzheimer’s biomarkers in the blood.”