Although past research has shown a link between renal dysfunction and cognitive impairment, a new systematic review shows that the presence of albuminuria specifically is also associated with an increased risk of developing cognitive impairment.

The meta-analysis of 22 studies, each with at least 100 participants, was carried out to assess renal dysfunction markers and evaluate their possible involvement in brain health.

Pooled results showed that individuals with albuminuria in their urine samples had a 35% higher risk for dementia or cognitive impairment compared with those who did not.

Interestingly, no significant association was found between increased dementia/cognitive impairment risk and another kidney function marker: estimated glomerular filtration rate (eGFR).

“I think the findings actually represent a positive message,” Kay Deckers, MSc, junior researcher at the School for Mental Health and Neurosciences at Maastricht University, the Netherlands, toldMedscape Medical News.

“Renal dysfunction appears to be a risk factor for dementia. But those with kidney disease can do something about this, such as with diet, exercise, and mental stimulation,” said Deckers. “You can take control of your own brain health.”

The results were published online December 14 in Neurology.

Similar Risk Profiles

“The kidneys and the brain, both being end organs, are susceptible to vascular damage due to broadly similar anatomic and hemodynamic features,” write the investigators.

In addition, dementia and chronic kidney disease (CKD) “share a similar risk factor profile including hypertension, diabetes mellitus, or hyperlipidemia, and in both conditions a high prevalence of small vessel disease, silent brain infarcts, white matter pathology, and microbleeds was reported,” they add.

Although a meta-analysis published in 2012 reported a 39% higher risk for cognitive impairment in patients with CKD, it included just 6 studies that only examined eGFR levels, note the current researchers. “Therefore, we took a broader approach.”

They originally identified 8494 abstracts published before August 1, 2016, before settling on 22 prospective studies that fulfilled all analysis criteria. All participants were at least 45 years of age and had completed at least 1 year of follow-up.

The main measurement of cognitive decline used was the Mini-Mental State Examination.

Pooled analysis of the five studies examining albuminuria outcomes, with a total of 27,805 individuals, showed that the odds ratio (OR) for cognitive impairment or dementia was 1.35 (95% confidence interval [CI], 1.06 – 1.73) for those with vs those without the protein (P = .015).

In the 8 studies evaluating eGFR, with a total of 36,636 participants, those who had levels less than 60 mL/min/1.73 m2 had a nonsignificant OR of 1.28 for cognitive impairment (95% CI, 0.99 – 1.65; P = .06).

There were also no significant associations for those with eGFR less than 45 mL/min/1.73 m2 or for those with levels between 45 and 59 mL/min/1.73 m2.

Because only two studies assessed eGFR of 60 to 89 mL/min/m2, “it was not possible to perform a meta-analysis” on this level, they note.

The investigators add that there was also “insufficient support” for evaluating effects from cystatin C. Despite “tentative evidence” for effects from creatinine clearance and serum creatinine levels, the low number of studies evaluating these markers made including them in the meta-analysis also impossible.

“More research is [now] needed to examine whether the association with albuminuria is causal or due to shared mechanisms, and to establish the underlying pathophysiology,” write the researchers.

Deckers added that going forward it’s important to monitor cognitive function in older patients with kidney problems. “This is important for cognitive impairment as well as for other diseases.”

He reported that the investigators will continue looking into this association, including plans for conducting several population-based studies.

“But for now, I think the message is that it’s not a causal relationship that we found, but there is an increased risk,” he said.

Brain-Kidney Commonality

Asked for comment on these findings, David Knopman, MD, professor of neurology at the Mayo Clinic, Rochester, Minnesota, noted that this was a meta-analysis, with that type of study’s inherent strength and weaknesses.

“A meta-analysis allows you to see smaller effects or variability of effects across studies,” Dr Knopman said to Medscape Medical News.

“However, it also usually tells us what we already know, which was the message from these original studies: that chronic kidney disease is associated with a higher risk of dementia,” he said. “But I found it interesting that albuminuria had a stronger effect than eGFR, which is important from a mechanistic point of view.”

Dr Knopman commented that “one needs to be careful” about drawing too-strong conclusions from the findings. That said, “I believe that albuminuria may have more commonality with the shared mechanisms between kidney and brain than does glomerular filtration rate.”

He added that the important question now is: What is going on in terms of causal mechanisms?

“I think understanding the relationship between blood vessel abnormalities and brain function is a premier area in late-life neurobiology,” said Dr Knopman. “And rather than looking at the kidney as a way of indirectly looking at the brain, it would be far better to look at the brain directly, if we had the tools to do so.”

When asked about a take-home message for clinicians, he said that it’s important to recognize that there’s a commonality between the brain and kidney — and that blood vessel damage in both can lead to “leakage of blood proteins into places they’re not supposed to be.”

The analysis was supported by the In-MINDD (Innovative Midlife Intervention for Dementia Deterrence) project, which is funded by the European Union’s Framework Program Seven. The study authors and Dr Knopman have disclosed no relevant financial relationships.

Neurology. Published online December 14, 2016. Abstract