Associations between retinal microvasculature and cognition in middle-aged adults with type 1 diabetes without overt neurological symptoms

• In middle-aged individuals with type 1 diabetes (T1D), cerebral small vessel disease (cSVD) relates to poorer cognition and retinal microvascular pathology on OCTA. • Whether early retinal microvascular changes associate with cognition in this population remains uncertain. • Larger foveal avascular zone (FAZ) was associated with poorer working memory in middle-aged individuals with T1D. Type 1 diabetes is a risk factor for retinal microvascular pathology, cerebral small vessel disease (cSVD), and cognitive deficits. In older individuals with type 1 diabetes, decreased vessel densities of superficial (SCP) and deep (DCP) retinal capillary plexuses have been associated with cognitive impairment. We assessed whether these associations are already evident in midlife among individuals without overt neurological symptoms. We also investigated whether cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs), manifestations of cSVD, modify these associations. We measured vessel density of the SCP and DCP, and area of foveal avascular zone (FAZ) in macular 3×3 mm optical coherence tomography angiography (OCTA) images and performed a comprehensive neuropsychological assessment and brain MRI in 153 adults with type 1 diabetes (age 46.4±7.5 years, diabetes duration 30.7±10.1 years). In univariate analyses, SCP, DCP, and FAZ were related to measures of processing speed and executive functions (standardized beta ranged from –0.29 to –0.19, p-values from <0.001 to 0.018). However, after adjusting for age and relevant clinical markers, only association between FAZ and a sensitive working memory task (standardized β =–0.25, p<0.05) remained significant. In interaction analyses, CMBs and WMHs did not modify these associations. Enlarged FAZ was associated with poorer working memory performance independently of confounding factors. Otherwise, age largely explained the associations between retinal microvascular structure and cognition in middle-aged individuals with type 1 diabetes without any overt neurological symptoms.