Progression of Coronary Artery Calcification Is Associated with Clinically Relevant Cognitive Impairment in Type 1 Diabetes

An increased risk of cognitive dysfunction has been identified in type 1 diabetes (T1D). The association between cardiovascular disease and dementia has been examined in the general population, but the relationship is not known in T1D. The study assessed the role of coronary artery calcification (CAC) on cognitive impairment in 148 mid-aged T1D patients from the Pittsburgh Epidemiology of Diabetes Complications Study cohort of childhood-onset T1D. Baseline CAC was measured in 1996-98 and repeated 4-8 years later (2000-06). Per extensive neuropsychological testing in 2010-13, 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). Mean age and T1D duration at first CAC measure were 37 and 29 years, respectively. In logistic regression models with backward selection, allowing for previously established risk factors for cognitive impairment in this T1D cohort (sex, T1D duration, BMI, HbA1c, ApoE4 status, ankle-brachial index, statin use, proliferative retinopathy, distal symmetric polyneuropathy, and CAD), initial CAC volume was associated with cognitive impairment (OR: 1.08, 95% CI: 1.02-1.15). In those with an initial CAC>0 (n=68), including both CAC volume and density scores in the model along with other risk factors, both CAC volume (positively OR: 1.21 (1.07-1.37)) and CAC density (inversely OR: 0.41 (0.18-0.93)) were associated with cognitive impairment. In those with repeated CAC measures (n=116), the annual progression of CAC volume (determined by Hokanson method) doubled the odds of having cognitive impairment (OR: 1.96 (1.18-3.28)).

Progression of CAC volume was independently associated with clinically relevant cognitive impairment in mid-age adults with long lasting T1D. In those with prevalent CAC, CAC density appears to protect against cognitive impairment when controlling for CAC volume.