Diabetes and Dementia: No Direct Link, But Increased Risk?

There is no direct relationship between the pathologic features of Alzheimer disease and diabetes mellitus (DM), according to a new study that shows no significant association between glucose intolerance, DM, or insulin resistance and amyloid-β accumulation in the brain.

However, it is reasonable to conclude that out-of-control DM, strokes, and myocardial infarctions can increase the risk of dementia, said lead author Richard J. O’Brien, MD, PhD, Professor of Neurology, and Chair, Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore.

“Primary care physicians need to treat vascular risk factors aggressively. We can’t cure Alzheimer disease, but we can prevent it from becoming symptomatic in some people by cutting down the vascular component,” Dr O’Brien told ConsultantLive.

Dr O’Brien and colleagues used data from the Baltimore Longitudinal Study of Aging, which assesses the effects of aging, including the effects on cognition and dementia. The analysis included 197 patients from a brain autopsy study who underwent at least 2 oral glucose tolerance tests and all of whom were cognitively and neurologically normal at study entry. They also analyzed 53 patients from an imaging study who underwent at least 2 glucose tolerance tests and in vivo assessment of fibrillary amyloid-β levels with the use of carbon 11–labeled Pittsburgh Compound B (¹¹C-PiB).

“We looked at 250 people who had multiple glucose tolerance tests during life and found that no measure of glucose or insulin abnormalities correlated with either brain amyloid (a marker for Alzheimer disease) on autopsy or using a PET scan ligand that can detect it,” said Dr O’Brien.

After adjustment for sex and age at death, there was no significant association between Alzheimer disease pathology and any measure of glucose or insulin homeostasis in the autopsy group. There also were no significant differences in fasting glucose, fasting insulin, fasting homeostasis model assessment, and other tests among those who had dementia and those who did not.

In the imaging cohort, there was no significant difference in mean cortical ¹¹C-PIB retention between those with low and high lifetime fasting or 120-minute measures of glucose, insulin, or insulin resistance.

Glucose intolerance did not affect Alzheimer disease pathology, even at its earliest stages, the authors suggested. The results appeared to be similar regardless of whether the patients were taking medications to manage DM, they noted.

“The majority of older people get demented because they have more than one thing wrong with their brain,” including Alzheimer pathology, atherosclerosis, and strokes, said Dr O’Brien.

It’s far more important that patients with DM “worry about the cardiovascular risk factors that accompany diabetes,” Dr O’Brien noted. “People with diabetes have increased vascular risk. Primary care physicians need to tell their diabetic patients to take care of their vascular risk factors. Vascular disease can tip over people who are carrying around asymptomatic Alzheimer disease pathology in their brains.”

This study was supported by grants from the National Institute on Aging (NIA); the Burroughs Wellcome Fund for Translational Research; and the Intramural Research Program, NIA, NIH.

The study results were published online July 29, 2013 in JAMA Neurology.