People with Type 1 Diabetes Show Signs of Accelerated Brain Aging Related to Cognitive Problems

The brains of people with type 1 diabetes show signs of accelerated aging that correlate with slower information processing, according to research led by the University of Pittsburgh Graduate School of Public Health.

The findings indicate that clinicians should consider screening middle-aged patients with type 1 diabetes for cognitive difficulties. If progressive, these changes could influence their ability to manage their diabetes. The study, funded by the National Institutes of Health (NIH), is online and will be published in the May 19 issue of the journal Neurology.

“The severity of cognitive complications and cerebral small vessel disease — which can starve the brain of oxygen — is much more intense than we expected, but it can be measured in a clinical setting,” said senior author Caterina Rosano, M.D., M.P.H., associate professor in Pitt Public Health’s Department of Epidemiology. “Further study in younger patients is needed, but it stands to reason that early detection and intervention — such as controlling cardiometabolic factors and tighter glycemic control, which help prevent microvascular complications — also could reduce or delay these cognitive complications.”

Type 1 diabetes usually is diagnosed in children and young adults and happens when the body does not produce insulin, a hormone that is needed to convert sugar into energy.

Dr. Rosano and her co-authors examined brain MRIs, cognitive assessments, physical exams and medical histories on 97 people with type 1 diabetes and 81 of their non-diabetic peers.

The people with type 1 diabetes were all participants in the Pittsburgh Epidemiology of Diabetes Complications Study, an ongoing investigation led by Pitt Public Health epidemiologist and study co-author Trevor Orchard, M.D., to document long-term complications of type 1 diabetes among patients diagnosed at Children’s Hospital of Pittsburgh of UPMC between 1950 and 1980.

The MRIs showed that 33 percent of the people with type 1 diabetes had moderate to severe levels of white matter hyperintensities (markers of damage to the brain’s white matter, present in normal aging and neurological disorders) compared with 7 percent of their non-diabetic counterparts.

On three cognitive tests that measure abilities such as information-processing speed, manual dexterity and verbal intelligence, the people with type 1 diabetes averaged lower scores than those without the condition.

Among only the participants with type 1 diabetes, those with greater volumes of white matter hyperintensities averaged lower cognitive scores than those with smaller volumes, though the difference was less pronounced.

This shows the MRI brain scans.

The MRIs showed that 33 percent of the people with type 1 diabetes had moderate to severe levels of white matter hyperintensities (markers of damage to the brain’s white matter, present in normal aging and neurological disorders) compared with 7 percent of their non-diabetic counterparts. Image adapted from the UPMC press release.

The associations held even when the researchers adjusted for high blood pressure and glucose control, which are conditions that can worsen diabetes complications.

The study identified signs of nerve damage, such as numbness or tingling in extremities, as a risk factor for greater volumes of white matter hyperintensities.

“People with type 1 diabetes are living longer than ever before, and the incidence of type 1 diabetes is increasing annually,” said lead author Karen A. Nunley, Ph.D., postdoctoral fellow in Pitt Public Health’s neuroepidemiology program. “We must learn more about the impact of this disease as patients age. Long-term studies are needed to better detect potential issues and determine what interventions may reduce or prevent accelerated brain aging and cognitive decline.”

About this neurology research

Additional authors on this study are Christopher M. Ryan, Ph.D., Howard J. Aizenstein, M.D., Ph.D., J. Richard Jennings, Ph.D., John Ryan, Ph.D., Janice C. Zgibor, R.Ph., Ph.D., Robert M. Boudreau, Ph.D., Tina Costacou, Ph.D., and Rachel G. Miller, M.S., all of Pitt; and John D. Maynard, M.S., of VeraLight Inc.

Funding: This research was supported by NIH grants R01 DK089028, R01 DK034818-25 and R01 HL101959.

Source: Allison Hydzik – UPMC
Image Source: The image is adapted from the UPMC press release
Original Research: Abstract for “White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes” by Karen A. Nunley, PhD, Christopher M. Ryan, PhD, Trevor J. Orchard, MBBCh, MMedSci, Howard J. Aizenstein, MD, PhD, J. Richard Jennings, PhD, John Ryan, PhD, Janice C. Zgibor, RPh, PhD, Robert M. Boudreau, PhD, Tina Costacou, PhD, John D. Maynard, MS, Rachel G. Miller, MS and Caterina Rosano, MD, MPH in Neurology. Published online April 22 2015 doi:10.1212/WNL.0000000000001582


Abstract

White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes

Objective: Although microvascular complications are common in type 1 diabetes mellitus (T1DM), few studies have quantified the severity, risk factors, and implications of cerebral microvascular damage in these patients. As life expectancy in patients with T1DM increases, patients are exposed to age- and disease-related factors that may contribute to cerebral microvascular disease.

Methods: Severity and volume of white matter hyperintensities (WMH) and infarcts were quantified in 97 middle-aged patients with childhood-onset T1DM (mean age and duration: 50 and 41 years, respectively) and 81 non-T1DM adults (mean age: 48 years), concurrent with cognitive and health-related measures.

Results: Compared with non-T1DM participants, patients had more severe WMH (Fazekas scores 2 and 3 compared with Fazekas score 1, p < 0.0001) and slower information processing (digit symbol substitution, number correct: 65.7 ± 10.9 and 54.9 ± 13.6; pegboard, seconds: 66.0 ± 9.9 and 88.5 ± 34.2; both p < 0.0001) independent of age, education, or other factors. WMH were associated with slower information processing; adjusting for WMH attenuated the group differences in processing speed (13% for digit symbol, 11% for pegboard, both p ≤ 0.05). Among patients, prevalent neuropathies and smoking tripled the odds of high WMH burden, independent of age or disease duration. Associations between measures of blood pressure or hyperglycemia and WMH were not significant.Conclusions: Clinically relevant WMH are evident earlier among middle-aged patients with childhood-onset T1DM and are related to the slower information processing frequently observed in T1DM. Brain imaging in patients with T1DM who have cognitive difficulties, especially those with neuropathies, may help uncover cerebral microvascular damage. Longitudinal studies are warranted to fully characterize WMH development, risk factors, and long-term effects on cognition.

“White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes” by Karen A. Nunley, PhD, Christopher M. Ryan, PhD, Trevor J. Orchard, MBBCh, MMedSci, Howard J. Aizenstein, MD, PhD, J. Richard Jennings, PhD, John Ryan, PhD, Janice C. Zgibor, RPh, PhD, Robert M. Boudreau, PhD, Tina Costacou, PhD, John D. Maynard, MS, Rachel G. Miller, MS and Caterina Rosano, MD, MPH in Neurology. Published online April 22 2015 doi:10.1212/WNL.0000000000001582

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