ADA Presidents' Select Abstract: Structural Neuroimaging and Cognitive Function in Long-Duration Type 1 Diabetes

Cognitive decline is an increasingly important complication in people with type 1 diabetes (T1D) as they age. We previously reported that compared with nondiabetic people, those with long-duration T1D have impaired cognitive function, similar to people with type 2 diabetes. To characterize factors associated with cognitive decline in people with T1D, 52 participants of the Joslin Medalist Study (“Medalists”) with T1D≥50 years, and 20 age-matched nondiabetic controls, underwent clinical evaluation, cognitive assessments, and neuroimaging (Alzheimer Disease Neuroimaging Initiative-3 protocol). Compared to controls, Medalists had 49.4 (±21.9) cm3 (p=0.03) lower total brain volume, and 2.7 (±0.8) cm3, 3.0 (±1.5) cm3 and 3.1 (±1.5) cm3 lower volumes (p<0.05), respectively, in the deep gray matter region (thalamus, putamen, caudate and globus pallidus), the Alzheimer disease signature region (hippocampus, parahippocampus, entorhinal cortex, inferior parietal lobule, precuneus and cuneus), and the occipital lobe. No significant differences were observed in frontal, temporal, or parietal lobe volumes. In assessing small vessel disease, the number of white matter hyperintensities (WMHs) or microvascular hemorrhages did not differ between Medalists and controls, nor did regional cerebral blood flow measures (via arterial spin labeling). Among Medalists, reduced total and all regional brain volumes were associated (p<0.05) with worse motor skills, female sex, lower education status, increased age, and longer diabetes duration. Increased WMHs were associated with worse renal function and higher coronary artery calcification scores. Volumes did not associate with other cognitive domains (recall, working memory, or executive function). These findings suggest that cognitive decline in people with long-duration T1D is related mainly to abnormalities in parenchymal CNS rather than neurovascular changes. Definitive confirmation of this finding by brain histopathology is underway. Disclosure H. Shah: None. M. Desalvo: None. A. Haidar: None. S. Jangolla: None. M. Yu: None. J. Gauthier: None. N.A. Ziemniak: None. I. Wu: None. T. Billah: None. L. Ning: None. A. Adam: None. Y. Rathi: None. G.L. King: Research Support; Janssen Research & Development, LLC. Funding National Institute of Diabetes and Digestive and Kidney Diseases (3P30DK036836-34S1); Thomas J. Beatson, Jr. Foundation