Retinal Alterations as Potential Biomarkers of Structural Brain Changes in Alzheimer's Disease Spectrum Patients

Brain Sci. 2023 Mar 8;13(3):460. doi: 10.3390/brainsci13030460.

Abstract

Retinal imaging being a potential biomarker for Alzheimer's disease is gradually attracting the attention of researchers. However, the association between retinal parameters and AD neuroimaging biomarkers, particularly structural changes, is still unclear. In this cross-sectional study, we recruited 25 cognitively impaired (CI) and 21 cognitively normal (CN) individuals. All subjects underwent retinal layer thickness and microvascular measurements with optical coherence tomography angiography (OCTA). Gray matter and white matter (WM) data such as T1-weighted magnetic resonance imaging and diffusion tensor imaging, respectively, were also collected. In addition, hippocampal subfield volumes and WM tract microstructural alterations were investigated as classical AD neuroimaging biomarkers. The microvascular and retinal features and their correlation with brain structural imaging markers were further analyzed. We observed a reduction in vessel density (VD) at the inferior outer (IO) sector (p = 0.049), atrophy in hippocampal subfield volumes, such as the subiculum (p = 0.012), presubiculum (p = 0.015), molecular_layer_HP (p = 0.033), GC-ML-DG (p = 0.043) and whole hippocampus (p = 0.033) in CI patients. Altered microstructural integrity of WM tracts in CI patients was also discovered in the cingulum hippocampal part (CgH). Importantly, we detected significant associations between retinal VD and gray matter volumes of the hippocampal subfield in CI patients. These findings suggested that the retinal microvascular measures acquired by OCTA may be markers for the early prediction of AD-related structural brain changes.

Keywords: Alzheimer’s disease; biomarker; cognitive impairment; diffusion tensor imaging; hippocampus subfields; optical coherence tomography angiography; retinal nerve fiber layer; vessel density; white matter integrity.

Grants and funding

This research was partly supported by National Natural Science Foundation of China (No. 82071186) and Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. 2022-LCYG-MS-05), National Key Research and Development Program of China (No. 2022YFA1105300) and Jiangsu Province Senior Health Project (No. LKZ2023014). None of the authors have a conflict of interest, financial or otherwise, directly or indirectly related to this work.