The risk of cognitive dysfunction in aging populations with type 1 diabetes (T1D) may be similar to that of people with type 2 diabetes, but it has not been well-characterized clinically. In the Joslin Medalist Study, a cohort of people with ≥ 50 years of T1D, cognitive dysfunction was previously shown to correlate with cardiovascular disease (CVD) and proliferative diabetic retinopathy (PDR). In a Medalist subset (n=129), we extended these findings by assessing the relationships of cognitive changes and other complications with vascular abnormalities in the retina, a developmental extension of the central nervous system. Medalists were evaluated with validated cognitive tests to assess psychomotor speed (PS), immediate memory (IM), delayed memory (DM), working memory (WM), and executive function (EF). Retinal optical coherence tomography (OCT) and OCT angiography were performed to obtain neural retinal layer thickness and vascular density for the superficial (SCP) and deep (DCP) retinal capillary plexuses. CVD and PDR were associated with worse IM (p=0.03) and decline in PS (p=0.01), respectively, adjusting for age, A1c, BMI, triglycerides and hypertension. Thinning of the retinal outer nuclear layer (ONL) was associated with PDR (p=0.04), CVD (p=0.02), worse IM (p=0.05) and PS (p=0.01), adjusted for sex, diabetes duration, PDR and visual acuity. CVD, PDR and DM severity were associated with decreased DCP density (p=0.04, p=0.0004, and p=0.002, respectively). Decreased density of the SCP was associated with worse dominant hand PS (p=0.01), adjusted for PDR, T1D duration, and visual acuity.
In summary, cognitive decline in people with long duration of T1D is associated with PDR and CVD, which is supported by shared specific retinal vascular imaging abnormalities, suggesting a potential common pathogenesis underlying these complications in T1D.
E. Wolfson: None. W. Fickweiler: None. K. Sampani: None. H. Shah: None. L.P. Aiello: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; KalVista Pharmaceuticals, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; KalVista Pharmaceuticals, Inc. Other Relationship; Self; Optos. J. Sun: Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Inc., Novo Nordisk Inc., Optovue, Inc., Roche Pharma. Other Relationship; Self; Merck Foundation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Roche Pharma. G.L. King: Research Support; Self; Janssen Pharmaceuticals, Inc.
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836, UL1RR025758-03, R24283, DK083957-01DP3, DK094333-01, T32DK007260); JDRF (17-2013-310)