Patterns of cerebral injury vary in those with dementia, diabetes

Patients with diabetes and dementia had more microvascular infarcts, increased interleukin-6 concentration.

Diabetes may be linked with a distinctive pattern of cerebral injury in patients with dementia, according to results of a study published in the Archives of Neurology. Based on these findings, the researchers suggested that diabetes therapy has an impact on cerebral pathology.

Researchers evaluated the brain autopsies of 196 deceased patients aged 65 years or older who had enrolled in the Adult Changes in Thought Study, an ongoing, prospective, longitudinal, community-based study of aging and cognitive decline. Biochemical tests of frozen brain tissue were available for 57 of the patients.

Each case was divided into one of four groups based on clinical information: patients with both diabetes and dementia; patients with diabetes without dementia; patients without diabetes with dementia; and patients without either disease.

Results showed that neuropathological and biochemical factors did not differ based on diabetes status among the 125 patients without dementia. However, among those with dementia (n=71), autopsy revealed two patterns of injury based on whether the participant had diabetes and received diabetes treatment. Those who had dementia and no diabetes had larger amounts of beta-amyloid build-up and greater free radical damage. Patients with dementia and diabetes had more microvascular infarcts and inflammation in neural tissue.

This pattern was related to diabetes treatment; those with dementia who received treatment for diabetes had a greater number of microvascular infarcts in deep cerebral structures and untreated patients with diabetes and dementia had beta-amyloid plaque load similar to patients with dementia but without diabetes, according to the study. The pattern was consistent for all indices of beta-amyloid deposition.

“These novel characterizations of two apparently different patterns of injury in dementia depending on diabetes status may have important etiologic and therapeutic implications,” the researchers wrote in a press release.

Previously published studies have documented that diabetes is a risk factor for dementia in older individuals. Researchers have proposed several possible mechanisms, such as direct effects of hyperglycemia, insulin resistance and insulin-induced beta-amyloid peptide amyloidosis in the brain, according to background information included in the study. – by Katie Kalvaitis

Arch Neurol. 2009;66:E1-8.

There is increasing evidence of an association between diabetes and dementia, including Alzheimer’s disease. Alzheimer’s disease is associated with increased beta-amyloid protein deposition in the brain; evidence is accumulating that insulin or insulin-like growth factor I may affect this accumulation. Apparently, from this study, patients without diabetes, but with dementia showed beta-amyloid accumulation whereas those with diabetes with dementia had more microvascular infarcts, the latter suggestive of diabetic vascular disease. Thus, the dementia in those with diabetes may indeed be more of a vascular complication when compared with dementia in those without diabetes, which stimulates the beta-amyloid deposits seen in Alzheimer’s disease. These differences may portend different therapeutic opportunities.

– Derek LeRoith, MD, PhD

Endocrine Today Editorial Board member