The Presence of Cerebral White Matter Lesions and Lower Skin Microvascular Perfusion Predict Decline in General Cognitive Ability in Type 1 Diabetes Patients but Not in Healthy Controls

Objective: Cognitive impairments in type 1 diabetes may result from hyperglycemia-associated cerebral microangiopathy. In this study we aimed to identify cerebral microangiopathy and skin microvascular dysfunction - as surrogate marker for generalized microvascular function - as predictors of cognitive decline over time.

Research Design and Methods: Twenty-five type 1 diabetes patients and 25 matched healthy controls underwent neurocognitive testing at baseline and after follow-up (mean duration of 3.8±0.8 years). At baseline, 1.5 T cerebral magnetic resonance imaging was used to detect white matter lesions (WML) and cerebral microbleeds. In addition, skin capillary perfusion was assessed by means of capillary microscopy. Multiple linear regression analysis was performed to examine if cerebral microangiopathy and capillary perfusion were associated with changes in cognitive performance.

Results: In type 1 diabetes patients, but not in healthy controls, the presence of WML (ß=-0.419;p=0.037) as well as lower skin capillary perfusion (baseline: ß=0.753;p<0.001; peak hyperemia: ß=0.743;p=0.001; venous occlusion: ß=0.675;p=0.003; absolute capillary recruitment: ß=0.549;p=0.022) at baseline were associated with decline in general cognitive ability over time, independent of age and sex, HbA1c and severe hypoglycemic events. The relationship between WML and cognitive decline was significantly reduced to non-significant levels after adjusting for capillary perfusion.

Conclusions: In type 1 diabetes patients, presence of WML and lower skin capillary perfusion predict poorer general cognitive ability over time. The relationship between WML and cognitive decline was significantly reduced when adjusting for capillary perfusion, suggesting that generalized microvascular dysfunction at least partly underlies WML-associated cognitive decline.