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’s d =0.39–0.54). Those with type 1 diabetes and ≥3 CMBs had smaller TBV, WMV, and volumes of cortex, thalamus, and nucleus accumbens, compared to those with 0–2 CMBs (Cohen’s 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, p ^FDR =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.

Twitter summary

In middle-aged adults with #Type1Diabetes, global and regional brain volumes together with cerebral microbleeds are associated with accelerated cognitive deficits. #Cognition #BrainMRI

Article highlights

• Why did we undertake this study?

  The interplay between cerebral small vessel disease, brain volumetric alterations, and cognition in type 1 diabetes remains unclear.

• What is the specific question(s) we wanted to answer?

  Does type 1 diabetes involve brain volume loss in middle age, is this loss related to cerebral microbleed (CMB) burden or cognitive deficits, and does CMB burden moderate the association between brain volume and cognition?

• What did we find?

  Several brain volumetric alterations were found, which were not directly related to cognitive changes. However, we observed negative synergistic interactions between brain volumetric changes and CMBs on cognitive outcomes.

• What are the implications of our findings?

  Microvascular pathology and structural brain volumetric alterations jointly contribute to cognitive impairment in type 1 diabetes.