Macular choriocapillaris perfusion area: a potential biomarker of mild cognitive impairment in patients with cerebral small vessel disease.

AIM: To develop and validate retinal vascular biomarkers for detecting mild cognitive impairment (MCI) in cerebral small vessel disease (CSVD) using swept-source optical coherence tomography angiography (SS-OCTA).

METHODS

Participants with MCI and normal cognition were prospectively enrolled from two ongoing cohorts (Dream-10 and FRESH-CSVD; NCT06164262 and NCT06431711). All participants underwent SS-OCTA and structural MRI (S-MRI). Individuals with Alzheimer's disease were excluded based on plasma biomarkers. Participants were split into development (January-August 2024) and temporal validation (September 2024-January 2025) cohorts. Feature selection was conducted using least absolute shrinkage and selection operator regression, followed by receiver operating characteristic analyses.

RESULTS

A total of 209 participants were included, with 48.8% (102/209) diagnosed with MCI. In the development cohort (n=136), the 3-6 mm macular choriocapillaris perfusion area (CCPA) of the left eye (oculus sinister, OS) showed superior diagnostic accuracy for MCI (AUC=0.906), outperforming S-MRI markers (all p<0.05). Temporal validation confirmed diagnostic accuracy (AUC 0.902; sensitivity 88.6%, specificity 81.3%) with minimal performance drift (ΔAUC 0.002). Adding S-MRI markers did not significantly enhance diagnostic performance (p>0.05). Both 0-3 and 3-6 mm OS macular CCPA were significantly associated with cognitive decline (Mini-Mental State Examination, Montreal Cognitive Assessment and Clinical Dementia Rating Sum of Boxes; all p<0.01), and mediation analyses suggested partial effects through white matter hyperintensity volume and right choroid plexus volume ratio.

CONCLUSION

SS-OCTA-derived macular CCPA, especially in the 3-6 mm OS region, may serve as a promising and non-invasive biomarker for CSVD-related MCI. Further multicentre studies are needed to establish its clinical applicability.