Brain volumes and their relationship with cerebral microbleeds and cognition in middle-aged adults with type 1 diabetes

Objective: Type 1 diabetes is related to an increased risk of structural brain alterations, cerebral microbleeds (CMBs), and cognitive deficits. We explored brain volumes and their direct and combined associations with CMBs on cognitive performance in middle-aged individuals with type 1 diabetes. Research Design and Methods: Adults with type 1 diabetes (n=163; mean age 46+/-8 years; diabetes duration 31+/-10 years; 53% women) and 48 matched controls underwent brain MRI and clinical and neuropsychological evaluations. Volumetric MRI measures adjusted to intracranial volume included total brain volume (TBV), white matter volume (WMV), and total volumes of cortex, thalamus, hippocampus, nucleus accumbens, and choroid plexus. Results: Individuals with type 1 diabetes had smaller TBV, WMV, and volumes of cortex, thalamus, and nucleus accumbens, and larger choroid plexus compared to controls (Cohen d=0.39-0.54). Those with type 1 diabetes and 3 or more CMBs had smaller TBV, WMV, and volumes of cortex, thalamus, and nucleus accumbens, compared to those with 0-2 CMBs (Cohen d=0.54-0.92). We found no direct associations between brain volumes and processing speed or executive functions. However, TBV, WMV, nucleus accumbens, and choroid plexus volumes had significant negative synergistic interactions with CMBs on processing speed and executive functions (standardized betas: -0.61 to -0.51 and 0.54 to 0.75, FDR-corrected p=0.006-0.048). Conclusions: Smaller global and regional brain volumes and larger choroid plexus volumes were found in middle-aged individuals with type 1 diabetes compared to healthy controls. Together with CMB burden, structural brain volumetric alterations were associated with accelerated cognitive deficits.