Reduced cortical gyrification in type 1 diabetes is associated with white matter integrity loss and cognitive decline

Type 1 diabetes-related cognitive declines suggest cortical involvement, despite cortical volume and thickness failing to account for these changes. The local gyrification index (LGI), which quantifies the complexity of cortical folding, could therefore provide additional information about cerebral integrity. This study aimed to determine differences in LGI in type 1 diabetes (T1D) in relation to the white matter integrity of connecting fibers and cognitive functioning. Fifty-one T1D participants with microangiopathy, 53 without, and 49 healthy controls underwent MR-imaging and neuropsychological assessment. LGI was calculated using FreeSurfer6. Probabilistic tractography was performed with MRtrix3. Group analyses were adjusted for age, sex, systolic blood pressure; and for multiple comparisons using Family Wise Error (FWE). Mediation analysis was performed with Python. LGI was broadly reduced across T1D participants, primarily driven by those with microangiopathy (all P_FWE < 0.05), especially in cortical areas connected by the arcuate fasciculus and forceps major. Lower LGI was associated with poorer arcuate fasciculus and forceps major integrity - tracts selected because their fibers connect the cortical regions exhibiting decreased gyrification in type 1 diabetes - and cognition (all P < 0.05). Mediation analyses revealed that cortical gyrification partly mediates the relationship between lower white matter integrity and reduced cognitive performance. LGI reductions had a posterior predominance in the brain in adults with T1D and microangiopathy, and associated with cognitive decrements and poorer white matter integrity. Mediation analyses further suggested a critical role of reduced cortical gyrification in linking lower white matter integrity to poorer cognitive performance.