Albuminuria Predicts Cognitive Decline in Diabetes

Megan Brooks

September 13, 2013

Albuminuria is a risk factor for cognitive decline in relatively young adults with diabetes and normal renal function, a new study suggests.

In the study, diabetic patients with persistent albuminuria over 4 to 5 years had greater declines in cognitive function than those without albuminuria.

"The cognitive decline was a subtle one of higher cognitive function, and not clinically apparent," first author Joshua Barzilay, MD, from Kaiser Permanente of Georgia in Duluth, told Medscape Medical News. However, over time it could translate into noticeable impairment, he said.

The study was published online and will appear in the November issue of the Clinical Journal of the American Society of Nephrology.

Novel Study

Prior studies have shown that albuminuria is associated with cognitive decline, including one reported by Medscape Medical News showing the correlation was independent of kidney function, but Dr. Barzilay said "several aspects of this study are new."

"The cohort here is purely diabetic. There is no admixture of diabetes with no diabetes. By age 60-65 years, 30% to 35% of people with diabetes have protein in the urine," he explained.

  "All of the cohort had normal cognitive function at baseline. Prior studies had people with and without cognitive impairment at baseline," he further noted. "Importantly, all the participants had normal renal function. All prior studies have been done in populations that included people with impaired renal function, which itself (independent of protein in the urine) may lead to cognitive decline."

Dr. Joshua Barzilay

This analysis included 2977 adults with diabetes from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD MIND) study. They had a mean age of 62 years and preserved baseline estimated glomerular filtration rate (eGFR, approximately 90 ml/min per 1.73 m2). They were recruited between August 2003 and December 2005 and were followed until June 2009. At baseline, 20 and 40 months, patients took standard neuropsychological tests.

The researchers report that patients with albuminuria at baseline and on at least 1 test at follow-up (persistent albuminuria) had a statistically significant percentage decline in processing speed on the Digit Symbol Substitution Test (DSST) over 40 months compared with those with no albuminuria (P = .001).

Patients with progressive albuminuria (no albuminuria at baseline, but albuminuria on at least 1 follow-up test) had a decline in DSST score that approached statistical significance compared with those without any albuminuria (P = .10). Both albuminuria groups had trends toward a decline in the Rey Auditory Verbal Learning Test (RAVLT), a test of verbal memory (P = .11 and P = .08, respectively).

Percentage Change in Cognitive Tests at 40 Months

Test Albuminuria (%) Progressors (%) No Albuminuria (%)
DSST –5.8 –4.1 –2.6
RAVLT 4.8 4.7 7.1


On logistic regression analysis, persistent albuminuria (odds ratio [OR], 1.37 [95% confidence interval (CI), 1.09 - 1.72]) and progressive albuminuria (OR, 1.25 [95% CI, 1.02 - 1.56]) were associated with a 5% or greater decline in information processing speed scores but not with verbal memory or executive function performance (Stroop test).

The findings were independent of baseline eGFR and declining eGFR, which were only mildly diminished (0.54 to 0.60 ml/min per 1.73 m2 per year) at the end of follow-up, leaving most participants with normal to near-normal renal function, the investigators note.

Implications Important From Population View

"These findings extend prior studies of the association of renal disease and cognitive decline to an even earlier stage of renal disease than previously reported," the authors say.

"Our finding was a subtle change in cognition; 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," Dr. Barzilay said in a statement.

In their article, the authors note that patients with persistent and progressive albuminuria had the equivalent of 7.2 and 3.2 years of cognitive aging relative to 1 year of calendar aging, respectively.

"Given how common albuminuria and diabetes are in the older population, these findings have a great deal of importance from a population point of view. Moreover, albuminuria is also common among older people with hypertension without diabetes," he said.

"Thus, using protein in the urine and a very sensitive test of cognitive function detects people with diabetes at risk for potential subsequent cognitive impairment," Dr. Barzilay told Medscape Medical News.

He also noted that because diabetes and albuminuria are vascular risk factors, "the findings suggest that an early mechanism for cognitive decline in people with diabetes is microvascular."

Strengths of the study include prospective data collection, repeated measures of cognitive testing, near-complete data capture, characterization of albuminuria over time, and a large number of participants.

The authors recognize that follow-up was short and may not be predictive of subsequent cognitive decline. A follow-up study called ACCORDION will add 3 to 5 years of follow-up, they say.

The ACCORD MIND study work was funded by the National Institutes of Health and the National Institute on Aging. The authors have disclosed no relevant financial relationships.

Clin J Am Soc Nephrol. Published online August 2013. Abstract


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