Advanced Brain Aging Observed in Older Type 1 Diabetes Patients Compared to Those Without

Article

This research supports the notion that brain morphology may be related to acceleration in the aging process for middle-aged and older-aged adults who have a long history of type 1 diabetes.

Mohamad Habes, PhD

Credit: Biggs Institute

Mohamad Habes, PhD

Credit: Biggs Institute

Advanced brain aging can be observed in those who have type 1 diabetes and no signs of Alzheimer’s disease or related degeneration, according to recent findings, compared to individuals without type 1 diabetes.1

These new findings were the result of a study examining regional brain atrophy patterns and brain aging patterns in adults who are either middle- or older-aged and have type 1 diabetes.

“Little is known about structural brain changes in type 1 diabetes (T1D) and whether there are early manifestations of a neurodegenerative condition like Alzheimer disease (AD) or evidence of premature brain aging,” the study’s investigators wrote.

The research was authored by Mohamad Habes, PhD, from the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at the University of Texas Health Science Center San Antonio.

Background and Findings

The investigators sought to assess neuroimaging markers of brain age and atrophy that resembled Alzheimer's disease in study participants with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study.2

This new study was done to identify the specific brain areas that undergo the most substantial changes in patients with type 1 diabetes and to examine the relationship between cognition and indicators of aging of the brain.

The cohort study utilized data which had been gathered during the combined DCCT (a randomized clinical trial conducted from 1983 - 1993) and EDIC (an ongoing observational study from 1994 onwards) studies conducted across 27 clinical centers in Canada and the US.

The investigators enrolled a total of 416 participants from the EDIC study with type 1 diabetes and 99 demographically similar adults without diabetes were enrolled in the magnetic resonance imaging (MRI) ancillary study.

The cross-sectional data the research team collected from 2018 - 2019 was assessed in relation to longitudinal measurements obtained from the DCCT/EDIC study. The data analysis took place between July of 2020 - April of 2022. The exposure variable in this study was a diagnosis of type 1 diabetes.

The main outcomes and measures of interest were decided to be psychomotor and mental efficiency, determined through tests such as a digit symbol substitution test, verbal fluency, trail making part B, and the grooved pegboard.

Immediate memory scores were then decided by the logical memory subtest of the Wechsler memory scale and the Wechsler digit symbol substitution test. Furthermore, MRI and machine learning techniques were employed by the team to calculate indices predicting brain age and quantifying atrophy resembling AD.

Overall, the investigators ended up with 416 individuals from the EDIC group, with a median age of 60 years, of which 21% were shown to be older than 65 years. These participants had a median diabetes duration of 37 years.

The research team found that in comparison to individuals without diabetes, the EDIC group participants consistently had higher brain age values, indicating an additional approximate 6 years of brain aging.

The team’s statistical analysis (β, 6.16; SE, 0.71) indicated a substantial difference between the EDIC and control groups (β, 1.04; SE, 0.04; P < .001). Despite this difference, there was not a significant difference in Alzheimer’s disease regional atrophy between the 2 groups.

The areas with atrophy in EDIC participants, compared to controls, were primarily observed by the investigators in the participants’ bilateral thalamus and putamen. Among the EDIC participants, a higher brain age was shown to be linked to lower psychomotor and mental efficiency (β, −0.04; SE, 0.01; P < .001), but the association was not observed among the control group.

“Brain atrophy is linked to changes in cognition, but overall, the differences seen in middle-aged to older-aged adults with T1D compared with controls without T1D were modest, even after more than a mean of 38 years of T1D,” they wrote.

References

  1. Habes M, Jacobson AM, Braffett BH, et al. Patterns of Regional Brain Atrophy and Brain Aging in Middle- and Older-Aged Adults With Type 1 Diabetes. JAMA Netw Open. 2023;6(6):e2316182. doi:10.1001/jamanetworkopen.2023.16182.
  2. Nathan DM, Genuth S, Lachin J, et al; Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986. doi:10.1056/NEJM199309303291401.
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