VIENNA — Markers of metabolic dysfunction are associated with changes in brain volume and cognition, suggesting that these prediabetic conditions accelerate brain aging, according to researchers who undertook a study of more than 2,000 subjects.
Subjects with these markers—hyperinsulinemia, hyperglycemia, and insulin resistance—had decreased total cerebral volume equivalent to 6 years' worth of structural brain aging, Dr. Zaldy S. Tan said at the International Conference on Alzheimer's Disease.
“These changes were seen even among nondiabetics,” said Dr. Tan, suggesting that metabolic dysregulation might affect the brain long before diabetes becomes clinically apparent.
Dr. Tan, of Harvard Medical School, Boston, and his colleagues based the study on data extracted from the Framingham Heart Study Offspring Cohort. This group consists of 5,124 men and women who are the children of the original Framingham cohort. They have undergone up to eight examinations since their cohort was established in 1975; exams are conducted every 4-6 years.
Dr. Tan and his colleagues focused on 2,518 participants who had attended the seventh examination cycle, were free of stroke and clinical dementia, and had undergone volumetric brain MRI and cognitive testing. Their mean age was 63 years; 269 had diabetes.
The researchers correlated MRI and cognitive measures with diabetes, fasting glucose levels, hemoglobin A1c, fasting insulin, and homeostatic model assessment–estimated insulin resistance (HOMA-IR). The models controlled for age, sex, education, stroke risk factors, ApoE4 status, and homocysteine, C-reactive protein, and interleukin-6 levels.
No correlates were found between metabolic dysfunction and hippocampal volume, but total cerebral brain volume was inversely correlated with diabetes, HbA1c, fasting insulin level, and insulin resistance. “These changes were equivalent to 6 years of structural brain aging, and persisted even among those without diabetes,” Dr. Tan said.
He also found an inverse correlation between executive function and diabetes, fasting glucose, HbA1c, fasting insulin level, and insulin resistance, in patients with and without diabetes.
Visual memory was inversely related to fasting insulin and insulin resistance, but there were no significant relationships between measures of metabolic dysfunction and verbal memory.
Two proposed mechanisms account for the association of diabetes and structural brain volume. Diabetes is a known vascular risk factor and might induce cerebrovascular brain injury, and eventual structural and cognitive brain aging. But even before diabetes arises, altered insulin levels in the brain also might exert a negative effect.
The conference was sponsored by the Alzheimer's Association.