Greater progression of coronary artery calcification is associated with clinically relevant cognitive impairment in type 1 diabetes

Background and aims: We assessed the predictive role of coronary artery calcification (CAC) in clinically relevant cognitive impairment in 148 middle-aged individuals with childhood-onset type 1 diabetes (T1D) from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. Methods: Baseline CAC was measured in 1996-98 and repeated 4-8 years later. Per extensive neuropsychological testing in 2010-15, 28% (41/148) of participants met the study definition of clinically relevant cognitive impairment (two or more of 7 select test scores >= 1.5SD worse than demographically appropriate published norms). Logistic regression models with backward selection were constructed for statistical analysis. Results: Mean age and T1D duration at first CAC measure were 37 and 29 years, respectively. A greater burden of initial CAC was associated with cognitive impairment determined 14 years later. Compared to Agatston score= 0, odds ratio (OR) and 95% confidence intervals (CI) of 0<-100, 100<-300 and> 300 were 1.4 (0.6, 3.6), 2.3 (0.6, 9.7), and 7.9 (1.6, 38.5), respectively. With both initial and progression of CAC in the multivariable model, backward selection retained only CAC progression, showing it was significantly associated with cognitive impairment (OR [95% CI]: 1.7 [1.1, 2.9]). In those with an initial CAC> 0, CAC density was marginally, inversely, associated with cognitive impairment when controlling for CAC volume (OR [95% CI]: 0.3 (0.1, 1.2), p value= 0.078). Conclusions: Greater CAC burden was associated with clinically relevant cognitive impairment in middle-aged adults with childhood-onset T1D. CAC progression appears to be a more powerful predictor than initial calcification.