Accelerated Brain Aging in Type 1 Diabetes Across Painful and Painless Peripheral Neuropathy: MRI-Based Brain Age Estimates From Deep Learning
Søren N.F. Hostrup,, Suganthiya S. Croosu,, Johan Røikjer,, Carsten D. Mørch,, Christina Brock,, Asbjørn M. Drewes,, Birgitte Brock,, Janusiya A. Muthulingam,, Tine M. Hansen,, Niels Ejskjaer,, Jens B. FrøkjærStructural brain alterations, including accelerated brain aging, occur in diabetes, as seen via MRI. The brain age gap (BAG) is likely caused by a combination of factors, including mechanisms associated with diabetic peripheral neuropathy (DPN) and neuropathic pain. In this study, 178 participants with type 1 diabetes (T1D) (n = 79 without DPN, 53 with painless DPN, 46 with painful DPN) and 48 healthy control individuals underwent structural brain MRI. Whole-brain and regional BAG were derived from the volBrain pipeline. Participants with T1D had an average of 3.5 years of increased BAG compared with healthy control individuals (P = 0.001). Subgroup analyses revealed increased BAG (6–7 years) for participants with DPN, regardless of the presence of pain, compared with participants with T1D without DPN and healthy control individuals (P < 0.001). Adjustment for diabetes duration attenuated group differences. Correlation analyses supported that diabetes duration was the primary driver of BAG. Sural nerve conduction velocity mediated only a 1.4-year increase in BAG. Regional effects showed a diffuse BAG distribution across the brain. These findings indicate that diabetes duration is a primary cause of accelerated brain aging in T1D, with a diffuse pattern across the brain, largely independent of painless or painful DPN. These exploratory results require validation in more rigorously characterized cohorts.
Article Highlights
Accelerated brain aging has been reported in diabetes, but its links with diabetic peripheral neuropathy (DPN) and neuropathic pain remain unclear. We explored brain age gap (BAG) in type 1 diabetes to determine if it differs across neuropathic phenotypes, relates to clinical characteristics including DPN measures, and shows distinct regional patterns. Diabetes participants had 3.5 years of BAG, rising to 6–7 years in those with DPN. Diabetes duration was the main driver of BAG, whereas DPN had limited impact and neuropathic pain no clear contribution. BAG was widespread across the brain. Accelerated brain aging appears to affect people with diabetes regardless of neuropathic complications.