Albuminuria Linked to Cognitive Decline in People With Diabetes

Microvascular disease in the kidney is paralleled by microvascular disease in the brain

Cognitive decline in patients with diabetes may be associated with microvascular changes in the kidneys, leading to microvascular changes in the brain, a new research study suggests.

Persistent albuminuria over approximately 3 years was linked to greater declines in cognitive function (specifically information processing speed) among patients ages 60 to 65 years with type 2 diabetes, according to a prospective study published online ahead of print in the Clinical Journal of the American Society of Nephrology.

“More than 35% of older adults with diabetes have albuminuria. Our study found that in such people with normal cognitive function, the presence of albuminuria—in the absence of any renal impairment—is associated with the development of subtle cognitive changes over 3 to 4 years of follow-up,” said Joshua Barzilay, MD, an internist at Kaiser Permanente of Georgia. “These cognitive changes are subtle and would not be noticed in day-to-day life. However, were the rate of this subtle decline to persist over another 10 to 15 years of follow up (ie, when people reach ages 75 to 80 years), then cognitive disability will become clinically noticeable,” Dr. Barzilay said.

“We know that patients with diabetes are at greater risk for cognitive diseases later in life as a group. The findings by Barzilay et al tell us that the presence of what would be considered early renal disease (ie, the presence of albuminuria in patients whose glomerular filtration rate is essentially normal) indicates a greater risk for other kinds of problems with aging—specifically, a more rapid decline in cognitive function,” commented Stephen L. Seliger, MD, Associate Professor of Medicine, University of Maryland School of Medicine, Baltimore, MD. In addition, the presence of albuminuria is probably reflective of a more generalized vascular problem, he said.

Study Design and Key Findings

The study involved nearly 3,000 patients (age ≥ 55 years; median age 62 years) enrolled in the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD MIND) study, which was designed to examine the effects of intensive glucose control on cognitive function. As a part of this study, participants underwent tests of information processing speed, verbal memory, and executive function at baseline, 20 months, and 40 months. The patients had normal renal function at baseline.

Patients with persistent albuminuria (ie, at baseline and follow-up) had significantly greater decreases in information processing speed than patients without albuminuria (-5.8% vs -2.6%; P=0.001). After adjusting for other potential confounding factors, persistent albuminuria (odds ratio, 1.37) and
progressive albuminuria (odds ratio, 1.25) were linked to a -5% decline in information processing speed scores, but were not significantly associated with verbal memory or executive function scores.

Strengths of the study include the relatively large patient population and the information available on comorbidities that allowed for adjustment for potential confounding factors, Dr. Seliger said. In addition, since neurocognition is not a unitary function, a strength of the study was the measurement of 3 different tests of cognition, he said. Limitations included a relatively modest follow-up period for the evaluation of cognitive function in patients who had relatively normal cognition at baseline, he said. Since the cognitive decline found in this study was moderate, the [impact] of this decline “is questionable,” he said.

Clinical Implications

Dr. Barzilay noted two main conclusions from the study: “1) cognitive decline in people with diabetes begins much earlier in life than in the mid-70s; and 2) early cognitive dysfunction has a microvascular origin in people with diabetes (ie, albuminuria is a marker of microvascular disease). We hypothesize that the microvascular disease in the kidney is paralleled by microvascular disease in the brain—endothelial dysfunction of blood flow and exudation of proteins into the brain tissue.”

“Although we tend to think in diabetes of specific kinds of complications (eg, renal abnormalities, neuropathy, retinopathy), in a sense the complications are all reflective of global vascular health, particularly microvascular,” Dr. Seliger said. “The findings remind us to take a holistic approach when we consider the vascular health of our diabetic patients and particularly in older diabetic patients. It reminds us that these [comorbities] are all connected, even if we are only looking at a renal problem,” he said.

“We do not have a specific treatment plan for a person with albuminuria that would protect against more rapid cognitive decline or the development of cognitive disease, but it might make us potentially have a higher index of suspicion that someone might develop cognitive problems later,” Dr. Seliger said. “That is particularly true if albuminuria is persistent. What we don’t know and, the study wasn’t designed to tell us, is whether treating albuminuria reduces the risk of cognitive decline,” he added.

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