Early cognitive decline, a dreaded complication of diabetes, is difficult and time consuming to diagnose. The Joslin Medalist Study, comprising individuals with ≥50 years of type 1 diabetes (T1D), reported that cognitive dysfunction was greater in T1D patients as compared to age-matched nondiabetic controls and was associated with proliferative diabetic retinopathy (PDR). We examined a larger Medalist sample to determine whether cognitive dysfunction is correlated with specific structural and vascular abnormalities in the retina, which embryonically is an extension of the central nervous system. Retinal imaging techniques such as optical coherence tomography (OCT) and OCT angiography (OCTA) can quantitate structural changes in individual retinal layers and the superficial and deep capillary plexus of the retinal microvasculature. We assessed Medalists (n=110) who underwent cognitive testing consisting of 5 validated measures in the following domains: executive functioning (EF), motor skills (MS), and immediate (IM), delayed (DM) and working memory (WM). Thinning of the neuroretinal ganglion cell layer (β: 0.69, P: 0.02) and inner plexiform layer (β: 0.56, P: 0.01) was associated with worse EF. PDR was associated with worse cognitive function (MS, dominant hand: OR: 1.02, P: 0.01; MS, non-dominant hand: OR: 1.01, P: 0.02; EF: OR: 0.83, P: 0.03) and decreased superficial retinal capillary plexus density (p=0.001). Decreased vessel density of the deep capillary plexus was associated with worse cognitive function including DM (β: 0.10, P: 0.01), IM (β: 0.10, P: 0.02), MS (dominant β: -0.07, P: 0.01; non-dominant β: -0.04, P: 0.03), even after adjusting for DR severity, T1D duration and visual acuity. These findings suggest that noninvasive ocular imaging techniques have potential to identify T1D individuals with early cognitive impairment, and provide insights into pathophysiological connections between cognitive function, diabetes and microvascular complications.
S.M. Paniagua: None. W. Fickweiler: None. V. Bahnam: None. K. Sampani: None. I. Wu: None. H. Shah: None. G. Musen: None. L.P. Aiello: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Decision Resources Group, KalVista Pharmaceuticals, Inc., Mingsight, Retinal Solutions. Stock/Shareholder; Self; KalVista Pharmaceuticals, Inc. Other Relationship; Self; Optos. J.K. Sun: Research Support; Self; Adaptive Sensory Technology, Boston Micromachines Corporation, Genentech, Inc., KalVista Pharmaceuticals, Inc., Optovue, Incorporated. Other Relationship; Self; Genentech, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc. G.L. King: Research Support; Self; Sanofi.
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836, UL1RR025758-03, R24283DK083957-01, DP3DK094333-01, T32DK007260); JDRF (17-2013-310); Thomas J. Beatson, Jr. Foundation Inc.