Combining OCT and OCT angiography improves differentiation of mild cognitive impairment and Alzheimer's disease

To evaluate retinal structural and vascular differences in probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography (OCT) and OCT angiography (OCTA), and to assess their combined performance in differentiating MCI/probable AD individuals with no cognitive impairment (NCI).

A cross-sectional study of 196 participants (NCI = 60; MCI = 83; probable AD = 53) recruited from two memory clinics, with good-quality OCT and OCTA scans, was conducted. Retinal layer thickness and vessel density were calculated using OCT/OCTA. Generalized estimating equations were used to compare groups, adjusting for relevant covariates. Receiver operating characteristic (ROC) curves assessed diagnostic accuracy.

Participants with MCI/probable AD were older (77 ± 6 years vs. 73 ± 9 years, p = 0.004) compared with controls, but sex distribution was similar (40% vs. 42% male, p = 0.796). The inner nuclear layer (β = 1.70 μm, p = 0.028) and inner segment/outer segment (IS/OS) layers (β = 0.51 μm, p = 0.003) were significantly thicker, while the outer nuclear layer was significantly thinner (β=-5.80 μm, p = 0.049) in MCI/probable AD participants compared to normal controls. OCTA showed reduced vessel densities in the superficial (β=-0.69%, p = 0.018) and deep capillary plexuses (β=-2.23%, p = 0.010), along with a larger deep foveal avascular zone perimeter (β = 0.18 μm, p = 0.038) in MCI/AD. Diagnostic performance was moderate for individual OCT (0.52-0.64) and OCTA layers (0.56-0.66). Combining OCT and OCTA significantly improved diagnostic accuracy (AUC = 0.90, p < 0.001), with a sensitivity of 81%, specificity of 87%, and highest Youden Index (0.67), compared to OCTA (0.55) and OCT (0.47).

Integrating OCT- and OCTA-derived metrics significantly improved discriminative performance compared with either modality alone, underscoring their complementary value in capturing distinct structural and vascular alterations associated with cognitive impairment.