<b>Accelerated Brain Ageing in Type 1 Diabetes across Painful and Painless Peripheral Neuropathy: MRI-Based Brain Age Estimates from Deep Learning</b>

<jats:p>&lt;p dir="ltr"&gt;Structural brain alterations occur in diabetes including accelerated brain ageing, using magnetic resonance imaging (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. 178 participants with type 1 diabetes (T1DM): 79 without DPN, 53 with painless DPN, 46 with painful DPN, and 48 healthy controls underwent structural brain MRI. Whole-brain and regional BAG were derived from the volBrain pipeline. Participants with T1DM had an average of 3.5 years of increased BAG compared to healthy controls (p=0.001). Subgroup analyses revealed increased BAG (6-7 years) for subjects with DPN, regardless of the presence of pain compared to participants with T1DM without DPN and healthy controls (p&lt;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 ageing in T1DM, with a diffuse pattern across the brain, largely independent of painless or painful DPN. These exploratory results require validation in more rigorously characterised cohorts.&lt;/p&gt;</jats:p>