New Marker for Risk of Cognitive Decline in Diabetes

Urinary protein levels may be an early marker of future cognitive decline in patients with type 2 diabetes (DM) and normal kidney function, according to a new study.

“We know that people with DM have a high incidence of microvascular complications in the eyes and kidney and that the microvascular circulations of the brain and of the kidneys share common elements. It therefore follows that microvascular disease of the kidneys-as detected by albuminuria-may provide insight into the microvascular processes in the brain that lead to cognitive decline,” Joshua Barzilay, MD, Clinical Professor of Endocrinology at Emory University School of Medicine in Atlanta and of Kaiser Permanente of Georgia, told ConsultantLive.

“People with DM have a 50% to 100% increased risk of cognitive impairment as compared to people without DM, much of which is microvascular in origin,” he added.

Several previous studies have shown that microvascular disease of the kidneys, as measured by spilling of protein in the urine, is associated with cognitive decline. “Our study is different in 3 ways,” said Dr Barzilay. “We have a homogeneous population of people with DM only, not a mixture of DM and non-DM. By age 60 to 65 years, up to one-third of those with DM have protein in the urine. Our population had no baseline cognitive impairment-they were all cognitively normal. The population had normal kidney function, that is, their kidneys were filtering blood normally. Many prior studies of urine protein and cognition included people with impaired renal function, which itself can lower cognition and modify the effects of urinary protein on cognition.”

By finding an association of albuminuria without renal impairment with cognitive decline, the study has extended previous studies of the association of renal disease and cognitive decline to an even earlier stage of renal disease than previously reported.

The researchers studied nearly 3000 patients with DM (average age, 62 years). Patients underwent 3 neuropsychological tests at the start of the study and again at 20 and 40 months. Tests included information processing speed, verbal memory, and executive function.

“The cognitive test that was abnormal in our study was the digit symbol substitution test, the test of information processing speed,” said Dr Barzilay. “It is a sensitive test for detecting subtle, early changes in higher cognitive function that will not be clinically apparent. We found an early decline in higher cognitive function with leaky kidney blood vessels. Since the presence of protein in the urine was associated with a 5% decline over 40 months in the DSST, it follows that were the rate of decline to continue linearly, or exponentially, by age 75 years the person could have lost 20% to 25% of this function if the decline were linear, and up to 50% were the decline exponential, which would translate into clinically evident cognitive disease.”

Dr Barzilay noted that the study did not assess the ability of urinary protein to predict future cognitive decline. That would require testing of sensitivity, specificity, and predictive values, which was not done.

Primary care physicians should tell their patients with DM about the risks of cognitive decline, Dr Barzilay said. “Diabetes is associated with microvascular complications. The presence of microvascular disease in the kidneys increases the likelihood of microvascular brain disease leading to cognitive decline.”

The researchers presented their results online in the August 29, 2013, issue of the Clinical Journal of the American Society of Nephrology.