1337-P: Improvement of Visual Acuity May Protect against Cognitive Decline and Cortical Atrophy in Long-Duration Type 1 Diabetes

Cognitive decline is a grave complication in aging people with type 1 diabetes (T1D). We previously reported that compared to individuals without diabetes, those with long-duration T1D, the Joslin “Medalists” cohort, have impaired cognitive function, similar to people with type 2 diabetes (T2D). We further reported that Medalists (n=52), with T1D≥50 years, mean age of 71 years, mean HbA1c of 6.8 %, a good lipid profile and controlled hypertension, had significantly lower brain volumes compared to age-matched controls (n=20) on brain MRI (Alzheimer Disease Neuroimaging Initiative-3 protocol), but no significant differences in neurovascular lesions. In this study, we demonstrate that among Medalists, reduced total and regional brain volumes were cross-sectionally associated (p<0.05) with female sex, worse psychomotor function and visual acuity, longer diabetes duration and higher inflammatory cytokines, but not with glycemic control (HbA1c, continuous glucose monitoring indices, advanced glycation end-products) or history of hypoglycemia. Interestingly, worse cognitive function and lower brain volumes, in addition to diabetic retinopathy, correlated selectively with thinning of the outer retinal nuclear layer (ONL, composed of photoreceptors) as assessed by Optical Coherence Tomography. Mediation analysis showed that psychomotor function mediated 58 % of the association between visual acuity and brain volume, and 44 % of the association between ONL thickness and brain volume. In a longitudinal subset (n=48), where Medalists had 2 or more cognitive visits with an average follow-up time of 4.8 years between visits, worse baseline visual acuity was associated with decline in psychomotor function over 3-5 years of follow-up. These findings suggest that future studies should investigate a potentially novel therapeutic approach of targeting improvement in visual acuity to prevent cognitive decline in people with long-duration T1D.