In people with diabetes but unimpaired glomerular filtration, protein in the urine is associated with cognitive decline even at a relatively young age, researchers reported.

In a prospective analysis, albuminuria was linked to declines in information processing speed, but not to worsening verbal memory or executive function, according to Joshua Barzilay, MD, of Kaiser Permanente of Georgia, in Duluth, and colleagues.

The drop in performance is small and probably not clinically relevant in the beginning, but might lead to measurable disability if the rate of decline persists, Barzilay and colleagues reported online in the Clinical Journal of the American Society of Nephrology.

“Our finding was a subtle change in cognition,” Barzilay said in a statement. “However, were this decline to continue over 10 to 15 years it could translate into noticeable cognitive decline by the age of 75 to 80 years, when cognitive impairment generally becomes clinically evident.”

He added that albuminuria and diabetes are common in older people, so the findings have “a great deal of importance from a population point of view.”

Barzilay and colleagues studied a subset of participants in the so-called ACCORD study, which tested the hypothesis that intensive glucose control in diabetics might yield better cardiovascular outcomes than usual care.

The 2,977 participants in the ancillary study - dubbed ACCORD-MIND - were studied to see if intensive glucose control might slow deterioration of cognitive function at an average age of 62.5.

Neither ACCORD nor ACCORD-MIND showed a benefit for intensive control, Barzilay and colleagues noted. However, to see if microvascular disease - as measured by albuminuria and decline in estimated glomerular filtration rate - was associated with cognitive decline, they compared outcomes over 3.3 years of follow-up among the ACCORD-MIND participants.

The main outcome measure was performance on the Digit Symbol Substitution Test, which measures information processing speed, but the investigators also had data on verbal memory and executive function from other tests.

Participants were defined as having persistent albuminuria if they had protein in their urine at baseline and at each of three tests during the study. They had progressive albuminuria if they did not have it at baseline but did later in the study.

Compared with the 57.1% of the participants without albuminuria, they found, the 15.9% with persistent albuminuria had a statistically significant decline in information processing speed.

Specifically, they had an average 5.8% decline on the Digit Symbol Substitution Test, compared with a decline of 2.6% for those without albuminuria (P=0.001).

Those who had progressive albuminuria showed a trend toward worsening processing speed, but it did not reach statistical significance, Barzilay and colleagues reported.

There were no significant changes in verbal memory or executive function associated with albuminuria, and no significant associations between estimated glomerular filtration rate and cognitive test results, they reported.

In logistic regression analysis, persistent albuminuria was associated with a 37% increase in the odds of at least a 5% decline in information processing speed scores (95% CI 1.09-1.72).

Similarly, progressive albuminuria was associated with a 25% increase in the risk of at least a 5% decline in processing speed (95% CI 1.02-1.56).

There were no associations with verbal memory or executive function performance.

Barzilay and colleagues cautioned that the findings don’t rule out other processes that might cause cognitive decline.

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Primary source: Clinical Journal of the American Society of Nephrology
Source reference: Barzilay JI, et al “Albuminuria and cognitive decline in people with diabetes and normal renal function” Clin J Am Soc Nephrol 2013; DOI: 10.2215/CJN.11321112.