Abstract
Subjective cognitive decline (SCD) serves as an initial symptom of preclinical Alzheimer's disease (AD). The accumulation of amyloid-beta (Aβ) is acknowledged as a critical risk factor for the eventual progression to mild cognitive impairment or dementia in individuals with SCD, highlighting the necessity for early detection and intervention. Previous studies have identified the retina and choriocapillaris as potential biomarkers for AD; however, these investigations have not thoroughly examined large and medium-sized choroidal vessels. Ultra-wide swept-source optical coherence tomography angiography (SS-OCTA), an innovative noninvasive imaging modality, facilitates rapid and precise quantitative assessment of retinal and choroidal boundaries and vasculature through dynamic scanning, encompassing large and medium-sized choroidal vessels. This study aims to characterize the outer retinal and choroidal vasculature and structure in individuals with SCD, examine the correlation between altered choroidal vasculature parameters and amyloid burden, and the presence of the apolipoprotein E (APOE) ε4 allele in SCD participants, to identify potential ocular biomarkers for high-risk SCD screening. In this study, 57 individuals with SCD and 45 matched normal controls were enrolled. Ultra-wide SS-OCTA was employed to assess the thickness of the outer retina and choroid and the blood flow within the choriocapillaris and large, medium-sized choroidal vessels. (18)F-Florbetapir positron emission tomography scans were performed to classify amyloid-positive-SCD (Aβ + SCD) and amyloid-negative-SCD (Aβ-SCD) groups. Plasma Aβ42/40 and APOE ε4 genotypes were also measured. Compared with normal controls, individuals with SCD exhibited a significant increase in the choroidal vessel index and a reduction in outer retinal thickness. The Aβ + SCD group demonstrated an elevated choriocapillaris flow area relative to the Aβ- SCD group. Moreover, a negative correlation was observed between the choriocapillaris flow area and plasma Aβ42/40 levels in the SCD cohort. Among SCD participants, APOE ε4 carriers displayed increased choriocapillaris flow area and choroidal vessel volume compared to APOE ε4 non-carriers. Our findings provide intriguing insights into the relationship between amyloid pathology and changes in the choriocapillaris flow area. The choroid may serve as a potential biomarker for screening Aβ + SCD.